Cancer Incidence in

Four Member Countries

(Cyprus, Egypt, Israel, and Jordan)

of the Middle East Cancer Consortium

(MECC)

Compared with US SEER

EDITED BY

LAURENCE S. FREEDMAN

BRENDA K. EDWARDS

LYNN A. G. RIES

JOHN L. YOUNG
ACKNOWLEDGMENTS

The editors and contributors gratefully acknowledge the following contributors to this monograph:

 • Gretchen Keel, David Roney, and other staff of Information Management Services, Silver Spring, MD, USA, for their part in 

preparing the data analyses and tables.

 • Paula Zeller, communications consultant, Olney, MD, USA, for technical editing. 

 • Terri Harshman, Surveillance Research Program, National Cancer Institute (NCI), Bethesda, MD, USA, for editorial assistance.

 • Milton Eisner and Marie-Josephe Horner, Surveillance Research Program, NCI, Bethesda, MD, USA, for technical assistance.

 • Donna Keen, Scientific Consulting Group, Gaithersburg, MD, USA, for reference support.

 • Dr. Joe Harford, Office of International Affairs, NCI, Bethesda, MD, USA, for supporting publication of this monograph.

We also thank the dedicated staff of the cancer registries of Cyprus, Gharbiah (Egypt), Israel, Jordan, and the SEER Program, without whose 

untiring efforts this monograph could not have been produced. 

CITATION

Suggested citation for this monograph:

Freedman LS, Edwards BK, Ries LAG, Young JL (eds). Cancer Incidence in Four Member Countries (Cyprus, Egypt, Israel, and Jordan) of the 

Middle East Cancer Consortium (MECC) Compared with US SEER. National Cancer Institute. NIH Pub. No. 06-5873. Bethesda, MD.

Citation for a chapter should also include the chapter authors and chapter title.

All material in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is 

appreciated. 

This publication is available on the SEER web site at http://seer.cancer.gov under Publications, and on the MECC web site at 

http://mecc.cancer.gov under Cancer Registry Project.

Front cover pictures (clockwise, beginning upper left):

Cyprus: 7th century Byzantine castle in Pathos, ruined by earthquake in 1222.



Egypt: Menkaure's Pyramid on Giza Plateau.



Israel: Jaffa Port, a seaport at least 3200 years old.



Jordan: Petra, an impressive facade carved into the rock more than 2000 years ago.

 
 MECC Monograph iii

Middle East Cancer Consortium

 Executive Director: Michael Silbermann (Israel)

 

 NCI Coordinator: Joe Harford (USA)

 Board of Governors Chairman: Samir Al-Kayed (Jordan)

 Board of Governors Members: Amal Samy Ibrahim (Egypt) Charitini Komodiki (Cyprus)

 Khamis Najjar (Palestinian Authority) 

 Rami Rahamimoff (Israel)

 Murat Tuncer (Turkey)

 Steering Committee for Joint

 Cancer Registration Committee

 Chairman: Laurence S. Freedman (Israel & USA) 

 Members: Samir Al-Kayed (Jordan) Micha Barchana (Israel)

 Brenda K. Edwards (USA) Sultan Eser (USA) Amal Samy Ibrahim (Egypt) Charitini Komodiki (Cyprus)

 Khamis Najjar (Palestinian Authority)

 Elaine Ron (USA) Abdel Razzaq Salhab (Palestinian Authority)

 John L. Young (USA)
iv MECC Monograph 

 

EDITORS AND CONTRIBUTORS

EDITORS

Professor Laurence S. Freedman, PhD Director, Biostatistics Unit, Gertner Institute for 

 Epidemiology and Health Policy Research, Tel Hashomer, Israel

Dr. Brenda K. Edwards, PhD Associate Director, Surveillance Research Program, Division of Cancer Control and 

 Population Sciences, National Cancer Institute, Bethesda, MD, USA

Ms. Lynn A. G. Ries, MS Statistician, SEER Program, National Cancer Institute, Bethesda, MD, USA

Professor John L. Young, DrPH Professor of Epidemiology and Director, Georgia Center for Cancer Statistics, 

 Rollins School of Public Health, Emory University, Atlanta, GA, USA

CONTRIBUTORS

Dr. Samir Al-Kayed, MD, FRCR Ministry Advisor for Cancer Affairs and Cancer Prevention Directorate, Chief of 

 Oncology Department, Ministry of Health, Amman, Jordan

Dr. Micha Barchana, MD, MPH Director, Israel National Cancer Registry, Jerusalem, Israel

Dr. Paolo Boffetta, MD, MPH Coordinator, Genetics and Epidemiology Cluster, International Agency for Research

 on Cancer, Lyon, France

 

Professor Dr. Ayhan O. Çavdar Chief, Cancer Working Group, Turkish Academy of Sciences, Turkey

Professor Gül Ergör, MD, MPH Dokuz Eylil University, Medical School, Department of Public Health, Izmir, 

 Turkey

Professor Amal Samy Ibrahim, MD, DrPH Professor of Epidemiology, Vice Dean Emeritus, National Cancer Institute, Cairo 

 University, Cairo, Egypt
 MECC Monograph v

CONTRIBUTORS (continued)

Dr. Peter D. Inskip, ScD Senior Investigator, Division of Cancer Epidemiology and Genetics, National 

 Cancer Institute, Bethesda, MD, USA

Professor Hussein M. Khaled, MD Dean, National Cancer Institute, Cairo University, Cairo, Egypt

Dr. Charitini Komodiki, MSc, PhD Chief Health Officer for Ministry of Health and Director, Cyprus Cancer Registry, 

 Nicosia, Cyprus

Professor M. Tezer Kutluk, MD, PhD Director, Haceteppe University Institute of Oncology, Ankara, Turkey

Dr. M. Bassam Qasem Epidemiologist, Deputy Director General for Primary Health Care, Ministry of 

 Health, Amman, Jordan

Professor Gad Rennert, MD, PhD Chairman, Department of Community Health and Epidemiology, Carmel Medical 

 Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel; Director, 

 CHS National Cancer Control Center; and Head, National Israeli Breast and

 Colorectal Cancer Detection Programs, Ministry of Health and Israel Cancer 

 Association

Dr. Elaine Ron, PhD Senior Investigator, Division of Cancer Epidemiology and Genetics, National 

 Cancer Institute, Bethesda, MD, USA

Dr. Cécile M. Ronckers Division of Cancer Epidemiology and Genetics, National Cancer Institute, 

 Bethesda, MD, USA

Professor Michael Silbermann, DMD, PhD Executive Director, Middle East Cancer Consortium, Haifa, Israel

Dr. Amr S. Soliman University of Michigan School of Public Health, Ann Arbor, MI, USA
vi MECC Monograph 

 
 MECC Monograph vii

 Table of Contents

Contents

Acknowledgments ii

Citation ii

Preface ix

Editors and Contributors

Editors iv

Contributors iv

Executive Summary

Major Findings xiii

Main Findings by Chapter xiii

Chapter 1: Overview and Summary Data

Background 1

The Registries 1

The Registry Populations 4

Data Collected by the MECC Registries 7

Registration Period 8

Statistical Methods 8

Summary Tables 13

References 27

Chapter 2: Esophageal Cancer

Background 29

Results 29

Summary and Conclusions 32

References 33

Chapter 3: Stomach Cancer

Background 35

Results 35

Summary and Conclusions 37

References 39

Chapter 4: Colorectal Cancer

Background 41

Results 43

Summary and Conclusions 46

References 48

Chapter 5: Liver and Intrahepatic Bile Duct Cancer

Background 51

Results 53

Summary and Conclusions 58

References 60

Chapter 6: Lung Cancer

Background 61

Results 62

Summary and Conclusions 66

References 66

Chapter 7: Laryngeal Cancer

Background 69

Results 70

Summary and Conclusions 71

References 72
viii MECC Monograph 

 Table of Contents

Chapter 8: Breast Cancer

Background 73

Risk Factors 73

Results 74

Discussion 76

Summary and Conclusions 78

References 79

Chapter 9: Cervical and Corpus Uterine Cancer

Background 83

Results 84

Summary and Conclusions 88

References 89

Chapter 10: Ovarian Cancer

Background 91

Results 91

Summary and Conclusions 93

References 95

Chapter 11: Urinary Bladder Cancer

Background 97

Results 102

Summary and Conclusions 107

References 109

Chapter 12: Brain and Other Central Nervous System Cancer

Background 111

Results 112

Summary and Conclusions 118

References 118

Chapter 13: Thyroid Cancer

Background 121

Results 121

Summary and Conclusions 129

References 129

Chapter 14: Lymphoma and Leukemia

Background 131

Results 132

Summary and Conclusions 137

References 139

Chapter 15: Childhood Cancer

Background 141

Results 142

Summary and Conclusions 148

References 149
 MECC Monograph ix

 Preface

In 1996, the Ministers of Health of Egypt, Israel, Jordan, Cyprus, 

and the Palestinian Authority (PA) signed an agreement to establish 

the Middle East Cancer Consortium (MECC). The U.S. Secretary 

of Health and Human Services witnessed the signature ceremony 

(Figure 1). Turkey joined the Consortium as a full member state in 

2004. The main goal of the new Consortium was to develop regional 

cooperation and to lessen the burden of cancer in the Middle East. 

After continuous deliberations, it was decided that the development 

of a cancer registration network across borders would be the first 

feasible project. Prior to the agreement, most of the countries in the 

Consortium had only recently begun to establish population-based 

registries, starting with, in most cases, hospital-based registries. 

Hence, by accelerating and strengthening this process, the Joint 

Cancer Registration Project very quickly became the flagship of 

MECC’s activities in the region.

MECC has either established or supported, along with the respective 

Ministries of Health, local centers for cancer registry covering 

the following populations: Jordan (registry situated in Amman); 

Gharbiah Region, Egypt (registry situated in Tanta); Israel (registry 

situated in Jerusalem); West Bank, PA (registry situated in Beit Jala, 

Bethlehem); Gaza Strip, PA (registry situated in Gaza City); Cyprus 

(registry situated in Nicosia); and Izmir, Turkey (registry situated 

in the city of Izmir). The major preliminary goal of educating and 

training a nucleus of registry staff in each country was achieved via 

courses in the region and in the United States, led by Dr. John Young 

of Emory University, Atlanta, Georgia. An additional important 

issue related to standardizing the coding and classification of the 

registration information and adopting one computer program that 

would enable comparative studies among the countries. With the 

support of the International Agency for Research on Cancer (IARC) 

in Lyon, France, the new MECC cancer registries began to use the 

CANREG program. This software was relatively easy to operate 

and had the constant backing of IARC staff (Drs. Andy Cook and 

 

 Figure 1. Ministers of Health, Geneva, 2000. From left to right: Mr. Frixos 

Savvides (Cyprus); Dr. Riad El-Zaanoun (Palestinian Authority); Dr. Donna 

Shalala, chair (United States); Dr. Ismail Salam (Egypt); and Mr. Shlomo 

Benizri (Israel). Not pictured: Dr. Faleh Al-Naser (Jordan), who was not 

present at that occasion. 
x MECC Monograph 

 Preface

Venkata Kumar) through electronic support and site visits to the 

Middle Eastern centers. 

To coordinate the work of this international group, Professor 

Laurence Freedman was appointed as chairman of the Steering 

Committee for the Joint Cancer Registration Project. Professor 

Freedman’s responsibilities were to provide overall supervision of 

the scientific direction of the project, maintain communications 

across borders, and organize the annual meetings of the Joint Cancer 

Registration Project, which initially rotated between the various 

capitals in the Middle East and IARC in Lyon. One person in each 

cancer registry center was appointed as principal investigator (PI), 

to serve on the Steering Committee and as the chairman’s contact 

person for ongoing issues. These PIs are Dr. Charitini Komodiki 

(Cyprus), Professor Amal S. Ibrahim (Egypt), Dr. Khamis Najjar 

(Gaza Strip, PA), Dr. Micha Barchana (Israel), Dr. Samir AlKayed (Jordan), Dr. Sultan Eser (Turkey), and Dr. Abdel Razzaq 

Salhab (West Bank, PA). The coordination was often difficult, 

due to circumstances in the region, but by and large it yielded 

very positive results, including, ultimately, this monograph. The 

frequent interactions between the PIs and the cancer registry staff 

in the MECC countries also served to develop better understanding 

between the individuals involved, including physicians, nurses, 

secretaries, statisticians, and others. 

The scientific aspects of the regional cancer registry program have 

been strongly supported by Dr. John Young; Dr. Elaine Ron of the 

Division of Cancer Epidemiology and Genetics, National Cancer 

Institute (NCI), Bethesda, Maryland; and Dr. Brenda Edwards, 

Associate Director, Division of Cancer Control and Population 

Sciences, NCI, and her dedicated staff. Drs. Young, Ron, and 

Edwards serve as members of the Steering Committee. 

The policies associated with the present and future work of the 

registry project are set by the MECC Board of Governors (one 

representative from each member state): Dr. Samir Al-Kayed, 

chairman (Jordan); Professor Amal S. Ibrahim (Egypt); Dr. 

Charitini Komodiki (Cyprus); Dr. Khamis Najjar (Palestinian 

Authority); Professor Rami Rahamimoff (Israel); and Professor 

Murat Tuncer (Turkey); together with the NCI coordinator, Dr. 

Joe Harford (United States) (Figure 2). The Board of Governors 

bears the responsibility of approving the annual budget for each 

center, adding special allocations for new equipment, assigning 

the budget for the annual meetings, and discussing all other 

initiatives and proposals associated with the registry project. The 

greater part of MECC’s annual budget is allocated to the registry 

project, and funds are channeled to MECC through NCI.

Because MECC is supported directly by the National Institutes 

of Health through NCI, which is a research institute, the 

expectations are always that the program will eventually yield a 

tangible scientific product. I believe that this monograph complies 

with the above expectations, and I do hope that it is only the 

first in a series of comprehensive publications related to cancer 

registration in the Middle East.

Michael Silbermann 

Executive Director

Middle East Cancer Consortium
 MECC Monograph xi

 Preface

 CHAIRMAN: Dr. Samir Al-Kayed, Jordan 

Prof. Amal S. Ibrahim 

Egypt 

Dr. Charitini Komodiki 

Cyprus 

Dr. Khamis Najjar 

Palestinian Authority 

Prof. Rami Rahamimoff

Israel 

Prof. Murat Tuncer 

Turkey 

 

 Figure 2. MECC Board of Governors 

MEMBER OF THE 

BOARD & 

COORDINATOR, NCI 

 Dr. Joe Harford 

United States

EXECUTIVE DIRECTOR 

Prof. Michael Silbermann 

MECC
xii MECC Monograph 
 MECC Monograph xiii

 Executive Summary

 

Cancer Incidence in Four Member Countries (Cyprus, Egypt, 

Israel, and Jordan) of the Middle East Cancer Consortium (MECC) 

Compared with US SEER is the first comprehensive publication of 

the MECC Cancer Registration Project. This monograph presents 

information about cancer incidence for populations in Cyprus, Egypt 

(Gharbiah Region), Israel (Jews and Arabs), and Jordan for the 

period 1996-2001. The MECC findings are compared with those 

from the US Surveillance, Epidemiology, and End Results (SEER) 

Program. 

For most of the cancers described in this monograph, incidence is 

expressed as age-standardized incidence rates (ASRs) per 100,000 

population. The ASR is a summary measure that permits comparison 

of incidence rates across populations while adjusting for differences 

in age distributions. ASRs for childhood cancers are expressed per 

1 million population.

MAJOR FINDINGS 

 • The overall incidence of cancer was substantially higher in the 

US SEER population and in Israeli Jews than in the other MECC 

populations. Cypriots, Israeli Arabs, and Egyptians had intermediate rates, while the Jordanian rates were the lowest. This pattern 

was seen for both males and females across the registries. 

 • Israeli Jews had the highest rate of colorectal cancer among the 

MECC populations, and their rate was higher than that of US 

SEER. The other MECC populations had rates less than half that of 

Israeli Jews. 

 • The incidence of liver cancer in Egyptians was more than 3 times 

that in US SEER and about 5 to 7 times that in the other MECC 

populations. 

 • Although overall lung cancer incidence in the MECC populations 

was much lower than in the US SEER population, younger Israeli 

Arab males (under 60 years of age) had rates comparable to those 

in US SEER.

 • Urinary bladder cancer incidence was very high among Egyptians and Israeli Jews, surpassing rates in the US SEER population. Egypt’s high rate is at least partly explained by the previously 

high prevalence of schistosomiasis, known to lead to squamous 

cell carcinoma of the urinary bladder. However, the currently high 

proportion of transitional cell carcinoma in Egypt may indicate a 

changing etiology of urinary bladder cancer in that population.

 • Non-Hodgkin lymphoma incidence was very high in Israeli Jews 

and Egyptians – higher than in US SEER, which was considered to 

have one of the highest rates worldwide. 

 • Childhood cancer incidence (under age 15 years) was high among 

Cypriots and higher than in the US SEER population. The high rate 

among Cypriots was mainly due to high rates of childhood leukemia and central nervous system malignancies. 

 • The incidence of childhood lymphoma was particularly high 

among Egyptians, compared with the other populations studied. 

MAIN FINDINGS BY CHAPTER

Chapter 1: Overview and Summary Data

 • The age distributions of the populations varied widely. The populations of Egyptians, Israeli Arabs, and Jordanians had higher proportions of young people (younger than 20 years) and lower proportions of older people (older than 50 years) than the populations of 

Cypriots, Israeli Jews, and US SEER. 

 • In the populations studied, cancer of the digestive system accounted for about 20% of all cancers, and cancer of the breast, about 

33% of female cancers – with relatively little variation across the 

populations.
xiv MECC Monograph 

 Executive Summary

 

 • Cancer of the male genital system (mostly prostate) accounted for 

as little as 4%-10% of male cancers in Egyptians, Jordanians, and 

Israeli Arabs, compared with 19%-33% in Israeli Jews, Cypriots, 

and the US SEER population.

 • The younger populations (Israeli Arabs, Jordanians, and Egyptians) 

had a greater proportion (16%-18%) of leukemias and lymphomas 

than the older populations (Cypriots, Israeli Jews, and US SEER) 

(7%-9%).

 • Two populations, US SEER and Israeli Jews, had substantially 

higher ASRs overall (318.6 and 274.4, respectively), compared 

with the others. The Cypriot (164.2), Israeli Arab (149.8), and 

Egyptian (143.0) populations had intermediate rates, while the 

Jordanian rates (113.3) were the lowest. This same pattern was seen 

for both males and females. 

Chapter 2: Esophageal Cancer

 • The incidence of esophageal cancer in the MECC countries was 

among the lowest in the world, with ASRs ranging between 0.6 

and 1.5, compared with 3.0 in US SEER. This may be related to 

the relatively low consumption of alcohol in the region. In contrast, 

there is a high prevalence of smoking in almost all of the MECC 

countries, which would tend to increase esophageal cancer rates. 

Further study seems warranted. 

Chapter 3: Stomach Cancer

 • Compared with the US SEER population (5.3), the ASR for stomach cancer was low among Egyptians (2.9); similar among Cypriots, Israeli Arabs, and Jordanians; and high among Israeli Jews 

(8.5). 

Chapter 4: Colorectal Cancer 

 • The ASR for colorectal cancer was particularly high among Israeli 

Jews (36.9), and higher than in the US SEER population (32.0). 

Other MECC populations had rates less than half that among Israeli 

Jews. The gap in incidence between the Israeli Jewish and US 

SEER populations was even greater in the 70-and-older age group. 

Chapter 5: Liver and Intrahepatic Bile Duct Cancer

 • The incidence of liver and intrahepatic bile duct cancer in Egyptians (12.8) was more than 3 times that in the US SEER population 

(4.2) and 5 to 7 times that in the other MECC populations. The 

high rates in Egypt may be related to the prevalence of hepatitis B 

and hepatitis C in the population or to contamination of food by 

aflatoxins. 

Chapter 6: Lung Cancer

 • The incidence of lung cancer in the MECC populations (9.9-20.4) 

was lower than that in the US SEER population (39.2). 

 • Age-specific rates of lung cancer among Israeli Arab males aged 

50 to 59 years (92.9) were comparable to those in the US SEER 

population (86.2). Israeli Arab men are known to have high tobacco 

consumption, and the high lung cancer rates at younger ages may 

reflect a cohort effect of rising rates in this population. 

 • The lung cancer ASR in Israeli Jews (19.0) was less than half that 

in the US SEER population (39.2). Yet, past records indicate higher 

rates of tobacco consumption among Israeli males than US males 

for the past 30 years. This possible anomaly calls for further study. 
 MECC Monograph xv

 Executive Summary

 

Chapter 7: Laryngeal Cancer

 • The incidence of laryngeal cancer in males in the MECC populations (1.6-3.1) was comparable to that in US SEER (2.7), although 

rates were somewhat higher in Israeli Arabs (3.1) and somewhat 

lower in Cypriots (1.6). This similarity between rates in MECC and 

US SEER merits further study. 

Chapter 8: Breast Cancer

 • The ASR of female breast cancer was high in Israeli Jews (93.1), 

comparable to that in the US SEER population (97.2). The other 

MECC populations had much lower rates (36.7-57.7). 

 • Age-specific rates of breast cancer among women under 55 years 

of age were higher in Israeli Jews than in the US SEER population. These high rates may be related to the genetic mutations in 

the BRCA genes known to be more prevalent among Ashkenazi 

women. 

Chapter 9: Cervical and Corpus Uterine Cancer

 • The incidence of cervical cancer was low in the MECC populations (2.5-5.3), substantially lower than in the US SEER population 

(7.0). This may be related to differences in sexual behavior between the populations. 

 • The incidence of corpus cancer and uterine cancer not otherwise 

specified was lower in the MECC populations (3.5-13.8) than in 

the US SEER population (17.6). Within MECC populations, the 

higher rates were found among Cypriots (11.8) and Israeli Jews 

(13.8). These results may be related to differences in the number of 

children born and the use of hormone replacement therapy in these 

populations. 

Chapter 10: Ovarian Cancer

 • The incidence of ovarian cancer in Israeli Jews (9.4) and Cypriots 

(7.7) was a little lower than that in the US SEER population (10.0). 

The rate was substantially lower in the other MECC populations 

(3.6-5.4). These differences may be related to differences in the 

number of children born in these populations. 

Chapter 11: Urinary Bladder Cancer

 • The incidence of urinary bladder cancer was very high in Egyptians 

(16.6) and Israeli Jews (15.1) – higher than the incidence in the US 

SEER population (12.2). The ASR was intermediate among Cypriots (11.2) and low among Israeli Arabs (8.6) and Jordanians (7.6). 

 • The high urinary bladder cancer rate in Egypt is at least partly 

explained by the previously high prevalence of schistosomiasis, 

known to lead to squamous cell carcinoma (SCC) of the urinary 

bladder. The proportion of SCC among all urinary bladder cancers 

was 26% in Egyptians, compared with 0%-2% in the other MECC 

populations and US SEER. Transitional cell carcinoma (TCC), the 

type of urinary bladder cancer found in most Western countries 

and associated with cigarette smoking, accounted for 63% of the 

urinary bladder cancers in Egypt and over 90% of the urinary bladder cancers in the other MECC populations and US SEER. That 

as much as 63% of the cancers in Egypt were TCC may indicate 

a changing etiology of urinary bladder cancer in that population. 

Further studies are indicated. 

 • The high rate of urinary bladder cancer in Israeli Jews may be related to high rates of cigarette smoking. This calls for further study. 
xvi MECC Monograph 

 Executive Summary

 

Chapter 12: Brain and Other Central Nervous System Cancer

 • The ASR of malignant brain tumors in Israeli Jews was identical to 

that in the US SEER population (4.9). The rates in the other MECC 

populations were somewhat lower (3.2-4.1). The higher rate in 

Israeli Jews may be related to the practice of head irradiation for 

tinea capitis, a treatment given to a substantial proportion of immigrant children entering Israel during the 1950s. 

Chapter 13: Thyroid Cancer

 • The ASR of thyroid cancer was higher in Israeli Jews (7.5) than in 

the US SEER population (6.2). The ASRs were moderate in Cypriots (5.6) and lower in Israeli Arabs, Egyptians, and Jordanians (2.0-

4.1). The ASR in Israeli Jewish women (11.2) was second only to 

that among Icelandic women (13.1), and may be related to the head 

irradiation treatment for tinea capitis received by many children 

immigrating to Israel during the 1950s.

Chapter 14: Lymphoma and Leukemia

 • The incidence rate of non-Hodgkin lymphoma was very high in 

Israeli Jews (15.2) and Egyptians (14.2) – higher than the rate in 

the US SEER population (12.9), which was considered one of the 

highest worldwide. The other MECC populations had lower rates 

(6.4-10.2). The reasons for the high rates in Israeli Jews and Egyptians are not well understood and require further study. 

 • The proportions of non-Hodgkin lymphomas that were extranodal 

did not differ widely across the populations studied (23%-36%).

 • The ASR of Hodgkin lymphoma was somewhat higher in most of 

the MECC populations (2.1-3.4) than in the US SEER population 

(2.4). Rates were highest among Israeli Jews (3.4) and Cypriots 

(3.0). 

 • The ASR of leukemia in Israeli Jews (8.6) was similar to that in the 

US SEER population (8.8). The rates in the other MECC populations were lower (6.0-6.9).

Chapter 15: Childhood Cancer

 • The ASR of childhood cancer (under age 15 years) was high among 

Cypriots (170.0 per million), compared with US SEER (153.3) and 

with the other MECC populations (114.8-133.3). 

 • Rates of childhood leukemia (under age 15) were highest among 

Cypriots (53.0) and the US SEER population (50.4). The rates in 

other MECC populations ranged from 29.4 to 39.2. 

 • The incidence of childhood lymphoma (under age 15) was particularly high among Egyptians (37.7), compared with the other populations studied, and was higher in MECC populations (15.7-24.2) 

than in the US SEER population (13.5). 

 • The incidence of childhood central nervous system malignancies 

(under age 15) was high in Cypriots (40.1) and higher than in the 

US SEER population (32.5). ASRs in other MECC populations 

were lower (16.5-24.2). 

 • Reasons for the high rates of childhood leukemia and CNS malignancies in Cypriots and the high rate of childhood lymphoma in 

Egyptians are not understood and call for investigation. 
 MECC Monograph 1

Overview and Summary Data Chapter 1

LAURENCE FREEDMAN, BRENDA K. EDWARDS, LYNN A. G. RIES, SAMIR AL-KAYED, MICHA BARCHANA, AMAL SAMY IBRAHIM, CHARITINI KOMODIKI, 

JOHN L. YOUNG

BACKGROUND

Cancer Incidence in Four Member Countries (Cyprus, Egypt, Israel, 

and Jordan) presents information on cancer incidence over the 

period 1996-2001, drawn from data collected by 4 registries in the 

Middle East – situated in Cyprus, Egypt, Israel, and Jordan – as part 

of the Joint Cancer Registration Project of the Middle East Cancer 

Consortium (MECC). This chapter provides background information 

to help readers better understand the data, the populations they 

describe, the way the data were collected, and their strengths and 

limitations. Tables in the latter part of the chapter provide an overall 

summary of the cancer incidence rates in the populations covered 

by the MECC registries and, for comparison, the Surveillance, 

Epidemiology, and End Results (SEER) registry program in 

the United States. Each succeeding chapter covers a particular 

anatomical site or histological type of cancer in more detail.

Three other registries participate in the MECC Cancer Registration 

Project, covering the populations of Gaza and the West Bank in 

the Palestinian Authority (PA), and of Izmir in Turkey. A condition 

for inclusion in this monograph was that the registry data had been 

checked by audit. Unfortunately, these registries have not yet been 

audited – the PA registries due to difficulties of access, and the Izmir 

registry due to its very recent participation in the project. It is hoped 

that these registries can be audited in the near future and will be 

included in future MECC publications. 

THE REGISTRIES

Cyprus National Cancer Registry

The Cyprus National Cancer Registry covers the population 

currently governed by the Government of the Republic of Cyprus 

(2001 population: 705,500), and not the Turkish-controlled part of 

the island. 

Collection of data on cancer incidence from histopathological 

reports was initiated in Cyprus in 1990. The population-based 

cancer registry was established in 1998, after Cyprus joined the 

MECC. From that time, the data collection and coding operation was 

redefined and strengthened.

Since its establishment, the Cyprus National Cancer Registry has 

functioned in Nicosia as a unit of the Ministry of Health. It is staffed 

with 3 tumor registrars and comes under the direct responsibility of 

the Chief Health Officer of the Ministry of Health. Tumor registrars 

actively collect data by regularly visiting the hospitals and their 

oncology departments, and reviewing cytology and bone marrow 

registers and the histology reports.

Cancer is not yet a notifiable disease in Cyprus, and death 

certificates in Cyprus are not sufficiently detailed to be used as a 

source for cancer registration. 

Gharbiah Regional Cancer Registry, Egypt

The Gharbiah Regional Cancer Registry, a population-based registry 

covering the Gharbiah Governorate, was established in 1998 within 

the context of the MECC Joint Cancer Registration Project. It is 

located in the Tanta Cancer Center of the Ministry of Health and 

Population. Tanta, the capital city of the Gharbiah Governorate, is 

situated in the middle of the Nile Delta, about 100 kilometers north 

of Egypt’s capital city, Cairo. The registry is jointly sponsored by 

MECC and the Ministry of Health and Population, Cairo. 

The registrar’s principal investigator is Professor Amal Samy 

Ibrahim, professor of epidemiology and past vice dean of the 
2 MECC Monograph 

Overview and Summary Data Chapter 1

National Cancer Institute in Cairo. The current executive director 

is Professor Hany Hussein, professor of pediatric oncology in the 

National Cancer Institute in Cairo and director of the Tanta Cancer 

Center. The previous executive directors are Dr. Kadry Ismail and 

Dr. Ahmed Hablas, both surgery consultants and previous directors 

of the Tanta Cancer Center. They currently act as co-investigators 

in the registry and are responsible for field supervision. The data 

managers are Dr. Ibrahim Abdel Bar, a surgery consultant at Tanta 

Cancer Center, and Dr. Mohammed Ramadan, a chemotherapy 

specialist at Tanta Cancer Center. They also supervise the daily 

activities of the registry, and are helped by 5 technicians and 

secretaries. 

Medical doctors of the Tanta Cancer Center actively collect data 

through regular visits to all governmental, non-governmental, and 

private centers and laboratories dealing with cancer patients. Data 

are also collected from death certificates. Centers outside Tanta that 

deal with cancer patients, mainly the National Cancer Institute in 

Cairo, are visited regularly to collect data on Gharbiah patients who 

might be treated there. 

Registration began in 1999. The registry records all incident cancer 

cases among the approximately 3.4 million residents of Gharbiah 

diagnosed within and outside the Gharbiah Governorate. Although 

notification of cancer is not obligatory by law, a Ministerial decree 

that was issued to request collaboration with the registry has 

enhanced data collection efforts. 

In the rest of this monograph, for convenience, we refer to 

Gharbiah as “Egypt.” The reader is to understand that this is 

merely a shorthand description, and that all results for Egypt in the 

monograph are derived from the Gharbiah subpopulation. 

Israel National Cancer Registry

The Israel National Cancer Registry, established in 1960, is 

part of the Center for Disease Control at the Ministry of Health 

of Israel. The main goal of this population-based registry is to 

maintain an updated, complete database on cancer incidence in the 

Israeli population. The registry provides data regarding incidence, 

prevalence, and survival, and is the basis for medical research, 

health planning, and monitoring of malignancies.

Reporting to the registry, which was voluntary prior to 1982, is now 

mandatory, and all Israeli hospitals (and since the late 1980s, also 

the private pathology laboratories) report, usually by submitting 

a copy of the medical documentation. Thus, the method of data 

collection is mostly passive, but when needed, registry staff visit 

reporting sources to collect data actively. 

Reporting sources include pathology, cytology, and hematology 

laboratories; hospital discharge forms; oncology institutes; death 

notification from district health offices; and the file of deaths from 

the Central Bureau of Statistics. Since 2000, through collaboration 

with the Israeli Hematology Society, all hematologists have been 

reporting the hematological malignancies that they see.

Several studies have been conducted to assess the registry’s 

completeness during its more than 40 years of operation. These 

studies began in the 1970s, with the latest one based on 1994 

data. The method used for these studies was to actively search for 

cancer patients in a defined period in all (or major) hospitals, and 

to compare the resulting data with the file in the registry (record 

linkage). These studies resulted in estimated completeness rates of 

over 94% (usually 95% and more) for solid tumors. In the latest 

study, a completeness rate of only 85%-90% was noted for non-solid 

tumors, resulting in the above-mentioned initiative to collaborate 

with the Israeli Hematology Society. One problem in these studies 

was that the Israel National Cancer Registry registers only Israeli 

citizens, but hospitals also treat non-Israeli patients.

The work at the registry is simplified by the existence of a unique 

identification number that is given to all Israeli citizens (at birth 

or immigration). This number, used by Israelis in all their contacts 
 MECC Monograph 3

Overview and Summary Data Chapter 1

with the health system and other government departments, prevents 

duplication of data. Each year, the registry receives a file containing 

all deaths in the country, which it uses to update the vital status of 

those in the register. 

The registry uses the International Classification of Diseases 

for Oncology, 3rd Edition (ICD-O-3) coding system for sites and 

histologies. Other parameters (such as stage of disease) are coded 

in accordance with the SEER Program, thus bringing the registry in 

line with MECC standards, which are described later in this chapter.

Jordan Cancer Registry

The population-based Jordan Cancer Registry was established in 

1996 under the umbrella of the Ministry of Health. Administration 

of the registry on a daily basis is the responsibility of the operations 

manager, under the supervision of His Excellency the Minister of 

Health. Much of the energy behind the establishment of the Registry 

was provided by Dr. Aref Bataynaha, the previous Minister of 

Health. Dr. Samir Al-Kayed (oncologist) and Dr. Bassam Al Hijawi 

(epidemiologist) pioneered the early work of the registry and set up 

its system of data collection. 

The registry is located in Amman, capital city of Jordan, with 4 

sub-offices: 1 located in Irbid in the Northern region, and 3 in 

large health institutions in Amman. The total number of staff in 

the registry is 11, of whom 3 are supported by a MECC grant. The 

remaining staff members are supported by the Ministry of Health. 

The staff members of the registry include an epidemiologist, a 

community health doctor, a statistician, data entry personnel, and a 

general secretary.

The registry covers the entire Jordanian population distributed 

over all 12 governorates, located in 3 regions. Amman includes 

approximately 38% of the total population.

Data for cancer registration are collected from all possible sources 

of information in the 4 health sectors: government, military, private, 

and university. Well-trained designated persons at each institution 

abstract cancer data from patients’ files, complete the notification 

forms, and forward them to the registry. The data collection system 

may therefore be described as partly passive. However, there is 

also an active component, implemented by the central registry staff 

through regular site visits to the health institutions, the frequency 

of visits determined according to the size of the institutions’ patient 

loads. Currently, 97 hospitals and 19 pathology laboratories notify 

cancer to the registry. 

Since its establishment, the registry has been fully computerized 

and has produced regular annual statistical reports that contain 

information on cancer incidence by age, sex, and type of cancer, as 

well as cancer trends. The reports are circulated widely throughout 

Jordan. The registry also has served as a focus for clinical and 

epidemiological research, and is increasingly used in planning 

oncology services such as radiotherapy units, a breast cancer 

mass screening program, cancer prevention and control programs, 

hospices, and palliative care activities. 

In 2003, the Ministry of Health declared by Public Health Law 

that cancer is a notifiable disease in Jordan, requiring all health 

institutions in all sectors to report cancer cases. Registry staff 

members are working in collaboration with the Civil Department 

to improve the quality of the national death certificate. It is hoped 

that this will help to collect better data on deaths where cancer is an 

underlying cause, and thereby on cancer mortality.

US Surveillance, Epidemiology, and End Results Program

The SEER Program of the National Cancer Institute (NCI) is an 

authoritative source of information on cancer incidence and survival 

in the United States (http://seer.cancer.gov). SEER currently 

collects and publishes cancer incidence and survival data from 

population-based cancer registries covering approximately 26% of 
4 MECC Monograph 

Overview and Summary Data Chapter 1

the US population. The SEER Program registries routinely collect 

data on patient demographics, primary tumor site, tumor morphology 

and stage at diagnosis, first course of treatment, and follow-up for 

vital status. The SEER Program is the only comprehensive source 

of population-based information in the United States that includes 

patient survival data.

SEER began collecting data on cancer cases in 1973 in the states 

of Connecticut, Iowa, New Mexico, Utah, and Hawaii, and the 

metropolitan areas of Detroit (Michigan) and San FranciscoOakland (California). In 1974-1975, the metropolitan area of Atlanta 

(Georgia) and the 13-county Seattle-Puget Sound (Washington) 

area were added. In 1978, 10 predominantly Black rural counties in 

Georgia were added, followed in 1980 by the addition of American 

Indians residing in Arizona. Three additional geographic areas 

participated in the SEER program prior to 1990: New Orleans, 

Louisiana (1974-1977, rejoined 2001); New Jersey (1979-1989, 

rejoined 2001); and Puerto Rico (1973-1989). The NCI also funds a 

cancer registry that, with technical assistance from SEER, collects 

information on cancer cases among Alaska Native populations 

residing in Alaska. In 1992, the SEER Program was expanded to 

increase coverage of minority populations, especially Hispanics, 

by adding the state of California’s Los Angeles County and 4 

counties in the San Jose-Monterey area south of San Francisco. In 

2001, the SEER Program expanded coverage to include Kentucky 

and the remaining counties in California (known as the Greater 

California registry); in addition, New Jersey and Louisiana once 

again became participants. For the expansion registries (Kentucky, 

Greater California, New Jersey, and Louisiana), NCI funds are 

combined with funding from the US Centers for Disease Control and 

Prevention (through the National Program of Cancer Registries) and 

with funding from the states. 

For this report, the SEER Program utilized cancer incidence data 

submitted to the NCI in November 2004 for cancer cases diagnosed 

in 1999-2001 from 13 population-based cancer registries that cover 

approximately 14% of the US population: Atlanta, Connecticut, 

Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, 

Seattle-Puget Sound, Utah, Los Angeles County, San Jose-Monterey, 

rural Georgia, and the Alaska Native Tumor Registry. Corresponding 

population data for these respective geographic areas come from the 

US Bureau of the Census.

The SEER Program is considered the standard for data quality 

around the world. Quality control has been an integral part of SEER 

Program activities since its inception. Currently, quality control 

studies of various types, including case finding, recoding, and 

reliability, are conducted every 1-2 years to evaluate the quality 

and completeness of the data being reported (SEER’s standard for 

case ascertainment is 98%). In some studies, a sample of cases is 

reabstracted to evaluate the accuracy of each of the data elements 

collected from the medical records. In other studies, targeted 

information gathering is performed to address specific data quality 

needs. Computer edits also are used by registries to ensure accurate 

and consistent data.

THE REGISTRY POPULATIONS

Many of the tables in this chapter and in the remainder of this 

monograph present statistics for each population side by side in 

the same table. The populations are arranged from left to right in 

the following order: Cyprus, Israel (Jews), Israel (Arabs), Egypt, 

Jordan, and US SEER. This order originally arose from a desire to 

place together MECC populations with similar age structure. Thus 

Cyprus and Israel (Jews) are placed adjacent to one another, and 

similarly Israel (Arabs), Egypt, and Jordan. US SEER is placed last 

as a comparison population, even though the population structure 

of the SEER geographic areas is similar to those of Cyprus and 

Israel (Jews). The Israeli population is subdivided into Israeli Jews 

and Israeli Arabs for the purpose of comparing cancer rates in the 2 

sectors within Israel, and also to allow comparisons between Israeli 

Arabs and the Arabs in neighboring countries. 
 MECC Monograph 5

Overview and Summary Data Chapter 1

Table 1.1. Overview and Summary Data: Number of Persons by 5-Year Age Group and Sex, Averaged over the Reporting Period, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER* 

1999-2001

Age Group Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 694,125 341,225 352,900 4,816,677 2,364,568 2,452,108 1,165,217 590,017 575,200 3,491,875 1,764,255 1,727,620 4,820,401 2,512,962 2,307,439 38,951,829 19,238,095 19,713,734

00-04 y 46,600 23,850 22,750 432,017 221,867 210,150 182,467 93,667 88,800 358,727 183,535 175,192 702,411 361,218 341,194 2,778,108 1,422,556 1,355,553

05-09 y 54,275 27,925 26,350 412,600 211,433 201,167 156,350 80,200 76,150 424,112 216,918 207,195 654,115 336,252 317,863 2,934,003 1,501,781 1,432,221

10-14 y 55,150 28,400 26,750 417,885 214,502 203,383 128,917 65,883 63,033 465,851 238,011 227,839 601,175 309,485 291,690 2,846,936 1,457,808 1,389,128

15-19 y 56,400 28,725 27,675 408,217 209,550 198,667 116,900 59,800 57,100 416,429 213,149 203,280 562,932 293,450 269,482 2,728,754 1,404,392 1,324,362

20-24 y 51,250 25,200 26,050 401,183 204,267 196,917 112,517 56,983 55,533 305,313 157,392 147,921 518,330 279,362 238,968 2,674,846 1,369,046 1,305,800

25-29 y 48,550 23,175 25,375 358,983 180,900 178,083 100,600 50,883 49,717 252,762 120,569 132,194 436,268 236,598 199,669 2,898,812 1,475,844 1,422,968

30-34 y 49,650 23,900 25,750 306,225 152,067 154,158 86,100 43,867 42,233 244,766 121,259 123,507 327,785 174,187 153,598 3,096,528 1,575,017 1,521,512

35-39 y 52,875 25,875 27,000 297,883 145,267 152,617 71,883 36,350 35,533 237,593 117,030 120,563 236,953 122,967 113,986 3,222,935 1,624,420 1,598,516

40-44 y 50,700 25,250 25,450 309,200 149,883 159,317 54,383 27,250 27,133 199,395 101,518 97,877 175,426 88,730 86,697 3,131,515 1,561,457 1,570,058

45-49 y 45,050 22,375 22,675 311,583 150,950 160,633 41,083 20,417 20,667 167,462 88,347 79,114 144,402 72,981 71,422 2,790,328 1,374,232 1,416,096

50-54 y 41,050 20,325 20,725 254,250 122,917 131,333 31,883 15,883 16,000 120,391 59,942 60,449 129,809 67,031 62,777 2,410,692 1,176,959 1,233,733

55-59 y 34,950 17,250 17,700 176,483 83,767 92,717 25,967 13,067 12,900 89,939 46,160 43,779 112,773 58,985 53,788 1,789,482 869,731 919,751

60-64 y 29,075 14,075 15,000 178,017 81,983 96,033 19,733 9,433 10,300 83,634 39,724 43,910 83,348 44,264 39,084 1,363,376 650,187 713,189

65-69 y 24,725 11,400 13,325 162,967 72,550 90,417 14,367 6,450 7,917 57,952 29,075 28,877 55,796 29,991 25,805 1,153,046 530,666 622,379

70-74 y 20,650 9,225 11,425 150,617 64,350 86,267 9,767 4,150 5,617 38,898 18,363 20,535 36,986 17,901 19,085 1,065,058 468,173 596,885

75+ y 33,175 14,275 18,900 238,567 98,317 140,250 12,300 5,733 6,567 28,652 13,264 15,388 41,894 19,561 22,333 2,067,409 775,826 1,291,583

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

Table 1.1 and Figure 1.1 present the number of persons in the 6 

populations (MECC and US SEER) subdivided by sex and 5-year 

age groups, averaged over the reporting period. 

The age distributions in these populations vary widely. The 

percentage of individuals under age 20 years is higher in Jordanians 

(52%), Egyptians (48%), and Israeli Arabs (50%) than in Cypriots 

(31%), Israeli Jews (35%), and the US SEER population (29%). 

Conversely the percentage over 50 years is lower in Jordanians 

(10%), Egyptians (12%), and Israeli Arabs (10%) than in Cypriots 

(26%), Israeli Jews (24%), and the US SEER population (25%). 

These profound differences in age distribution make it difficult to 

compare cancer incidence across the countries using crude incidence 

rates; therefore, this monograph uses age-standardized and agespecific incidence rates for purposes of comparison (see “Statistical 

Methods”). 

Table 1.1 also shows clear differences in the size of the populations 

covered by the registries. US SEER has the largest population; the 

Jordanian, Israeli Jewish, and Egyptian populations are intermediate; 

and the Israeli Arab and Cypriot populations are the smallest. The 

size of the population influences the total number of cancer cases 

registered, although other important factors also govern this number 

(see ”Statistical Methods”). 
6 MECC Monograph 

Overview and Summary Data Chapter 1

250 200 150 100 50 0

Thousands

Age Group

Population

75+

70-74

65-69

60-64

55-59

50-54

45-49

40-44

35-39

30-34

25-29

20-24

15-19

10-14

5-9

0-4

0 50 100 150 200 250

Thousands

30 25 20 15 10 5 0

Thousands

0 5 10 15 20 25 30

Thousands

Age Group

Population

75+

70-74

65-69

60-64

55-59

50-54

45-49

40-44

35-39

30-34

25-29

20-24

15-19

10-14

5-9

0-4

400 300 200 100 0

Thousands

0 100 200 300 400

Thousands

Age Group

Population

75+

70-74

65-69

60-64

55-59

50-54

45-49

40-44

35-39

30-34

25-29

20-24

15-19

10-14

5-9

0-4

250 200 150 100 50 0

Thousands

Age Group

Population

75+

70-74

65-69

60-64

55-59

50-54

45-49

40-44

35-39

30-34

25-29

20-24

15-19

10-14

5-9

0-4

0 50 100 150 200 250

Thousands

100 80 60 40 20 0

Thousands

Age Group

Population

75+

70-74

65-69

60-64

55-59

50-54

45-49

40-44

35-39

30-34

25-29

20-24

15-19

10-14

5-9

0-4

0 20 40 60 80 100

Thousands

3 2 1 0

Millions

0 1 2 3

Millions

Age Group

Population

75+

70-74

65-69

60-64

55-59

50-54

45-49

40-44

35-39

30-34

25-29

20-24

15-19

10-14

5-9

0-4

Figure 1.1. Overview and Summary Data: Age Distributions in Cyprus, Israel (Jews and Arabs), Egypt, 

Jordan, and US SEER - 1996 - 2001

Egypt Cyprus Jordan

Israel (Jews) Israel (Arabs) US SEER

Females Males
 MECC Monograph 7

Overview and Summary Data Chapter 1

DATA COLLECTED BY THE MECC REGISTRIES

Data Items

The collection of data by the MECC registries is guided by the 

Manual of Standards for Cancer Registration [1]. The manual 

specifies that certain data items are required for registration, while 

others are optional. The list of required items includes the following: 

identification number, sequence number, age at diagnosis, date of 

birth, sex, residential status, date of diagnosis, basis of diagnosis, 

primary site code (ICD-O-3), histologic type, behavior and grade, 

and summary stage.

Inclusion Criteria

For the purposes of this monograph, only those diseases that carry 

an ICD-O-3 behavior code 3 – i.e., those defined as malignant, with 

one exception noted below – are counted as cancer. Within this 

rubric, certain cancers are excluded, namely, basal or squamous 

cell carcinomas of the skin (which are very numerous in certain 

populations but almost always nonlethal). Note that, because of 

the behavior code exclusion, cervical intra-epithelial neoplasia 

and various carcinomas in situ are not counted here, even though 

they are recorded at MECC registries. Furthermore, some MECC 

registries record cases of benign brain tumors, but these too are 

not counted in this monograph. The one exception to the rule of 

including only behavior code 3 is the inclusion of in situ bladder 

carcinomas. 

Cancer registries use special rules to decide whether to separately 

count multiple tumors developing in the same person. Although 

all the MECC countries follow the rules for counting multiple 

primary tumors suggested by the International Association of 

Cancer Registries (IACR), US SEER follows slightly different rules. 

The major differences are that the SEER Program considers each 

segment of the colon and rectum a separate primary site, each skin 

site a separate primary site, and, in general, each breast a separate 

organ/primary site. Therefore, the rates for colorectal cancers, 

melanomas, and breast cancers may be slightly higher for SEER than 

for those registries utilizing the IACR rules.

Data Quality

MECC has regularly conducted exercises to check the quality and 

standardization of coding across the registries. These exercises 

have indicated that although some data items are already reliably 

recorded, others still have some way to go toward achieving the 

required quality. Specifically, age at diagnosis, major anatomical 

site (the 3-digit code where the leading “C” is counted as one of the 

digits – e.g., C34 for Bronchus and Lung), and major histological 

type are reliably recorded; summary stage is not. For this reason, 

summary stage information is not included in this monograph. 

Equally important to a successful and meaningful population-based 

registry program is the completeness of coverage of the population; 

that is, a high proportion of the cancers diagnosed in the population 

need to be registered. MECC has instituted an external audit 

program that checks this important issue. The registries participating 

in this monograph have all been checked by audit and have shown 

rates of coverage above 90% for the populations concerned. 

The quality of data in a population-based cancer registry can be 

judged by various statistical measures. One measure, the proportion 

of cases identified solely by death certificate, cannot be applied 

universally across the MECC registries because death certificates 

in Cyprus do not carry sufficient information to be used as a source 

for registration. Another such measure, the proportion of cases that 

are microscopically verified, is shown in Table 1.2 for the various 

populations and for the major sites and subsites of cancer. Generally 

speaking, a high proportion is considered to indicate high quality, 

but proper interpretation should take into account the level of 

diagnostic facilities available to and used by the population, and 

the clinical conventions used for diagnosing cancer. For example, a 

population with an extensive screening program for prostate cancer 
8 MECC Monograph 

Overview and Summary Data Chapter 1

using prostate-specific antigen may include individuals whose 

cancer diagnosis and treatment are based solely on the results of 

a clinical test, thus leading to a higher proportion of clinically 

diagnosed prostate cancers. Similarly, in some populations, 

diagnosis of lung cancer by radiological imaging might be deemed 

sufficient for diagnosis in some fairly common clinical situations 

(e.g., advanced tumors in the elderly). In such a population, a very 

high proportion of histologically or cytologically diagnosed cases 

would be an indication that clinically diagnosed cases are being 

missed. 

The data in Table 1.2 indicate generally higher rates of microscopic 

confirmation in Cyprus, Jordan, and the US SEER populations than 

in Israel and Egypt. The most likely explanation for the lower rate 

of microscopic confirmation in Egypt is that the medical facilities 

afforded to that population rely less on histology or cytology and 

more on clinical investigations for diagnosing malignancy than in 

other MECC populations. The most likely explanation for the lower 

rate of microscopic confirmation at the Israel registry is that the full 

details of the medical record are not always provided by the hospital 

to the registry. For some cancers in Israel, where the diagnosis may 

have been made by histology or cytology and the abstractor is not 

sure which, an unknown category is coded – the same code used for 

cases where the basis of diagnosis is completely unknown. Because 

these cases become indistinguishable from cases with diagnoses of 

unknown origin, they are therefore counted as “not microscopically 

confirmed.” Now that this problem has been revealed, future coding 

practice will be revised to avoid this confusion. 

Conversely, in some registries and for some cancers, percentages 

of microscopic confirmation are unrealistically high, which might 

indicate clinical cases that are missed because persons did not attend 

hospital or for other reasons. 

These observations demonstrate that although the MECC data 

included in this monograph have reached accepted standards, they 

still need to be interpreted with an understanding of their potential 

weaknesses and idiosyncrasies. 

REGISTRATION PERIOD

In this report, the period covered by each registry differs, in large 

part due to the age of the registry. The Israel and Jordan registries 

cover the 1996-2001 period, the Cyprus registry covers 1998-2001, 

and the Egypt and US SEER registries cover 1999-2001. MECC has 

determined that these between-registry differences in the reporting 

period do not cause serious bias in the comparisons of incidence 

rates in its populations. Such bias could occur only if there were 

dramatic changes in incidence rates over the short span of 6 years 

(1996-2001), and there is no such indication.

STATISTICAL METHODS

The simplest measure of cancer incidence, the annual crude 

incidence rate, is equal to the number of incident cases divided by 

the person years at risk. However, this measure is greatly influenced 

by the age distribution of the population, and as explained earlier 

under “The Registry Populations,” the age distributions in the 

MECC populations vary widely. Two other statistical methods allow 

a fair comparison of the incidence rates in different populations 

when the age distributions differ: (1) annual age-specific incidence 

rates and (2) annual age-standardized incidence rates. 

The definition of the annual age-specific incidence rate is simply 

the annual crude incidence rate within a narrowly defined (usually 5-

year) specific age group. When these rates are provided, population 

incidence rates may be compared within age groups. Comparisons 

done in this fashion are often informative, but a comparison over the 

16 age groups (from 0-4 years to 75+ years) is often cumbersome 

and arduous. 
 MECC Monograph 9

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

All sites 96.2% 95.5% 96.9% 85.3% 83.5% 87.0% 86.3% 86.0% 86.7% 81.6% 78.4% 84.9% 98.5% 98.4% 98.7% 95.1% 95.2% 95.0%

 Oral cavity and pharynx 97.8% 100.0% 94.3% 93.8% 93.6% 94.0% 95.1% 95.8% 93.8% 96.4% 97.7% 94.8% 98.4% 97.6% 100.0% 98.7% 98.8% 98.3%

 Lip 100.0% 100.0% - 96.1% 95.4% 96.9% 95.3% 96.4% 93.3% 80.0% 100.0% - 98.3% 97.7% 100.0% 99.6% 99.5% 100.0%

 Tongue 100.0% 100.0% 100.0% 94.3% 95.5% 93.2% 100.0% 100.0% 100.0% 96.8% 97.4% 95.8% 98.2% 97.1% 100.0% 98.9% 99.0% 98.7%

 Salivary gland 94.4% 100.0% 90.9% 90.6% 91.1% 90.1% 81.8% 84.6% 77.8% 96.4% 96.4% 96.4% 100.0% 100.0% 100.0% 99.0% 99.2% 98.7%

 Floor of mouth 100.0% 100.0% 0.0% 97.0% 100.0% 91.7% - - 0.0% 100.0% - - 92.9% 88.9% 100.0% 99.4% 99.4% 99.2%

 Gum and other mouth 100.0% 100.0% 100.0% 93.0% 94.3% 91.6% 95.0% 92.3% 100.0% 98.8% 100.0% 97.7% 100.0% 100.0% 100.0% 98.3% 98.4% 98.1%

 Nasopharynx 91.7% 100.0% 80.0% 90.6% 90.8% 90.1% 100.0% 100.0% 100.0% 97.2% 100.0% 90.9% 98.2% 97.5% 100.0% 97.9% 99.0% 95.6%

 Tonsil 100.0% 100.0% - 93.9% 91.7% 100.0% 100.0% 100.0% 0.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 99.6% 99.7% 99.3%

 Oropharynx - - 0.0% 90.7% 92.0% 88.9% 100.0% - - 100.0% - 100.0% 100.0% 100.0% - 97.6% 98.0% 96.8%

 Hypopharynx 100.0% - - 91.7% 88.6% 100.0% 100.0% 100.0% - 96.4% 100.0% 91.9% 92.9% 88.9% 100.0% 99.0% 98.9% 99.5%

 Other oral cavity 

 and pharynx 100.0% - - 80.8% 76.5% 88.9% 100.0% - - 75.0% 57.1% 100.0% - - - 89.1% 89.0% 89.4%

 Digestive system 95.5% 96.4% 94.5% 84.2% 85.2% 83.1% 86.0% 85.1% 87.2% 59.7% 58.2% 62.7% 98.5% 98.7% 98.4% 92.9% 93.5% 92.3%

 Esophagus 100.0% 100.0% 100.0% 85.4% 86.7% 83.6% 95.0% 100.0% 83.3% 88.3% 93.1% 80.6% 97.9% 97.0% 100.0% 96.1% 96.8% 94.3%

 Stomach 99.0% 98.2% 100.0% 89.9% 90.5% 88.9% 93.2% 95.4% 89.9% 79.6% 81.0% 77.5% 98.8% 98.8% 98.8% 96.8% 97.8% 95.2%

 Small intestine 100.0% 100.0% - 94.1% 95.9% 91.6% 88.5% 86.7% 90.9% 82.1% 75.0% 91.7% 100.0% 100.0% 100.0% 98.1% 98.6% 97.5%

 Colon and rectum 99.0% 99.7% 98.2% 91.4% 91.9% 90.9% 91.5% 92.0% 90.9% 84.6% 84.7% 84.5% 99.0% 99.5% 98.5% 97.5% 98.0% 97.0%

 Colon excluding rectum 98.7% 99.6% 97.9% 90.5% 91.2% 89.9% 90.8% 90.9% 90.7% 78.3% 78.7% 77.8% 98.9% 99.3% 98.4% 97.1% 97.6% 96.7%

 Cecum 98.6% 100.0% 97.4% 94.8% 94.5% 95.1% 95.8% 92.3% 100.0% 96.0% 92.9% 100.0% 100.0% 100.0% 100.0% 98.8% 99.1% 98.6%

 Appendix 100.0% 100.0% - 98.3% 100.0% 97.4% 75.0% - - - 0.0% - 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

 Ascending colon 100.0% 100.0% 100.0% 96.5% 96.3% 96.6% 100.0% 100.0% 100.0% 94.1% 100.0% 83.3% 100.0% 100.0% 100.0% 98.7% 98.9% 98.6%

 Hepatic flexure 100.0% 100.0% 100.0% 95.7% 97.3% 94.4% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 93.8% 100.0% 83.3% 99.3% 99.7% 98.9%

 Transverse colon 100.0% 100.0% 100.0% 95.9% 97.0% 94.8% 93.3% 100.0% 88.9% 85.7% 72.7% 100.0% 98.0% 95.8% 100.0% 98.9% 99.1% 98.8%

 Splenic flexure 100.0% 100.0% 100.0% 95.2% 96.8% 93.7% 85.7% 66.7% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 98.6% 98.9% 98.2%

 Descending colon 100.0% 100.0% 100.0% 96.1% 96.3% 95.9% 96.2% 93.8% 100.0% 82.6% 78.6% 88.9% 100.0% 100.0% 100.0% 98.8% 99.2% 98.3%

 Sigmoid colon 99.4% 100.0% 98.8% 95.4% 95.7% 95.1% 97.3% 96.1% 98.3% 96.1% 93.5% 100.0% 99.6% 100.0% 99.3% 99.0% 99.1% 98.9%

 Colon, NOS‡ 97.4% 98.8% 96.1% 75.4% 77.1% 73.7% 75.0% 77.1% 73.1% 60.0% 62.7% 56.7% 98.5% 99.1% 97.9% 63.1% 68.2% 58.7%

 Rectum and junction 99.6% 100.0% 99.0% 93.9% 93.8% 94.0% 92.7% 93.8% 91.4% 96.8% 96.6% 97.1% 99.3% 100.0% 98.6% 98.6% 98.9% 98.1%

 Rectosigmoid junction 97.8% 100.0% 94.4% 95.2% 95.6% 94.7% 92.3% 95.5% 88.2% 95.6% 96.6% 93.8% 99.4% 100.0% 98.6% 98.9% 99.2% 98.5%

 Rectum 100.0% 100.0% 100.0% 93.5% 93.1% 93.8% 92.9% 93.3% 92.2% 97.3% 96.6% 98.1% 99.3% 100.0% 98.6% 98.4% 98.8% 97.9%

 Anus, anal canal,

 and anorectum 100.0% 100.0% 100.0% 96.0% 96.4% 95.5% 100.0% 100.0% 100.0% 93.5% 86.7% 100.0% 100.0% 100.0% 100.0% 99.5% 99.7% 99.3%

 Liver and intrahepatic 

 bile duct 89.9% 94.2% 76.5% 56.4% 59.4% 52.3% 73.4% 68.8% 87.5% 40.7% 42.3% 34.5% 97.9% 97.9% 97.8% 71.8% 72.6% 70.2%

 Liver 90.0% 93.2% 81.3% 60.8% 63.3% 57.1% 72.6% 68.1% 86.7% 40.5% 42.1% 34.3% 98.0% 97.7% 98.6% 72.0% 72.7% 70.2%

 Intrahepatic bile duct 88.9% 100.0% - 21.2% 19.6% 22.6% - - - 50.0% 50.0% - 96.4% 100.0% 94.1% 70.9% 71.6% 70.1%

 Gallbladder 97.6% 100.0% 96.2% 79.3% 74.3% 80.5% 89.7% 75.0% 93.5% 68.8% 62.5% 75.0% 99.5% 98.2% 100.0% 92.4% 88.8% 93.7%

 Other biliary 100.0% 100.0% 100.0% 70.2% 74.2% 66.1% 54.8% 52.6% 58.3% 52.9% 51.7% 54.5% 98.0% 96.7% 100.0% 87.5% 90.9% 83.7%

 Pancreas 67.5% 74.3% 56.8% 43.8% 45.6% 41.9% 58.4% 61.0% 52.8% 30.2% 31.7% 28.2% 92.9% 94.5% 90.0% 77.1% 80.1% 74.2%

 Retroperitoneum 100.0% - - 83.7% 81.8% 85.7% 100.0% 100.0% 100.0% 91.2% 86.7% 94.7% 100.0% 100.0% 100.0% 98.7% 98.8% 98.6%

 Peritoneum, omentum, 

 and mesentery 100.0% 0.0% 100.0% 89.2% 95.3% 87.2% 100.0% - 100.0% 100.0% 0.0% 100.0% 96.8% 93.3% 100.0% 99.0% 100.0% 98.9%

Table 1.2. Overview and Summary Data: Proportions of Microscopic Confirmation, by Site and Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001*
10 MECC Monograph 

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

 Other digestive organs - - 0.0% 80.2% 91.2% 67.2% 81.8% 66.7% 100.0% 80.0% 84.6% 73.1% 100.0% 100.0% 0.0% 82.2% 86.8% 78.0%

 Respiratory system 92.0% 91.5% 94.4% 81.8% 82.7% 80.0% 85.5% 87.0% 76.1% 81.7% 82.9% 78.1% 97.6% 97.4% 98.2% 90.5% 91.4% 89.4%

 Nose, nasal cavity, 

 and middle ear 100.0% 100.0% 100.0% 93.2% 94.6% 91.5% 90.0% 83.3% 100.0% 96.7% 100.0% 94.1% 100.0% 100.0% 100.0% 98.3% 98.7% 97.8%

 Larynx 98.3% 100.0% 83.3% 90.2% 91.5% 82.3% 92.0% 93.2% 77.8% 91.0% 93.2% 66.7% 98.6% 98.5% 100.0% 98.4% 98.6% 97.7%

 Lung and bronchus 90.9% 90.1% 94.5% 80.2% 80.7% 79.1% 84.1% 85.6% 74.7% 77.2% 77.8% 75.4% 97.2% 97.1% 97.6% 89.9% 90.6% 89.0%

 Pleura 100.0% 100.0% - 93.6% 94.2% 92.6% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 95.4% 95.4% 95.2%

Trachea, mediastinum, 

and other respiratory 

organs 100.0% 100.0% 100.0% 85.6% 86.3% 84.4% 87.5% 100.0% 60.0% 83.3% 85.7% 80.0% 95.2% 92.9% 100.0% 92.6% 92.8% 92.2%

 Bones and joints 92.7% 92.9% 92.3% 87.6% 88.9% 85.7% 88.6% 92.0% 84.2% 79.5% 83.0% 75.0% 97.6% 98.2% 96.6% 97.4% 97.6% 97.2%

 Soft tissue including heart 93.0% 95.8% 89.5% 91.0% 92.6% 89.0% 89.2% 87.7% 91.1% 94.9% 98.3% 91.6% 99.1% 99.2% 99.0% 98.3% 98.5% 98.0%

 Skin excluding 

 basal and squamous 97.3% 100.0% 95.1% 93.1% 93.4% 92.7% 96.7% 96.2% 97.4% 100.0% 100.0% 100.0% 98.3% 98.1% 98.5% 99.0% 98.7% 99.5%

 Melanoma of the skin 97.9% 100.0% 96.4% 93.3% 93.4% 93.2% 97.7% 96.2% 100.0% 100.0% 100.0% 100.0% 97.7% 95.7% 100.0% 99.6% 99.5% 99.6%

 Other non-epithelial skin 93.3% 100.0% 83.3% 92.3% 93.3% 90.5% 95.7% 96.3% 95.0% 100.0% 100.0% 100.0% 98.9% 100.0% 96.2% 95.4% 93.9% 98.6%

 Breast 98.7% 100.0% 98.7% 91.9% 83.3% 92.0% 92.9% 90.9% 92.9% 93.5% 88.5% 93.5% 99.4% 100.0% 99.4% 98.9% 99.6% 98.9%

 Female genital system 98.5% 0.0% 98.5% 91.6% 0.0% 91.6% 88.9% 0.0% 88.9% 88.7% 0.0% 88.7% 99.2% 0.0% 99.2% 97.3% 0.0% 97.3%

 Cervix uteri 98.6% 0.0% 98.6% 92.6% 0.0% 92.6% 87.0% 0.0% 87.0% 99.0% 0.0% 99.0% 99.5% 0.0% 99.5% 98.8% 0.0% 98.8%

 Corpus and uterus, NOS‡ 99.6% 0.0% 99.6% 94.7% 0.0% 94.7% 94.4% 0.0% 94.4% 83.1% 0.0% 83.1% 99.0% 0.0% 99.0% 98.9% 0.0% 98.9%

 Corpus uteri 99.5% 0.0% 99.5% 97.4% 0.0% 97.4% 98.6% 0.0% 98.6% 98.1% 0.0% 98.1% 99.1% 0.0% 99.1% 99.4% 0.0% 99.4%

 Uterus, NOS‡ 100.0% 0.0% 100.0% 80.4% 0.0% 80.4% 69.6% 0.0% 69.6% 71.4% 0.0% 71.4% 98.9% 0.0% 98.9% 73.2% 0.0% 73.2%

 Ovary 96.5% 0.0% 96.5% 86.4% 0.0% 86.4% 77.3% 0.0% 77.3% 85.7% 0.0% 85.7% 99.2% 0.0% 99.2% 93.6% 0.0% 93.6%

 Vagina 100.0% 0.0% 100.0% 96.5% 0.0% 96.5% 100.0% 0.0% 100.0% 100.0% 0.0% 100.0% 100.0% 0.0% 100.0% 98.3% 0.0% 98.3%

 Vulva 100.0% 0.0% 100.0% 91.7% 0.0% 91.7% 83.3% 0.0% 83.3% 100.0% 0.0% 100.0% 100.0% 0.0% 100.0% 98.9% 0.0% 98.9%

 Other female 

 genital organs 0.0% 0.0% 0.0% 87.4% 0.0% 87.4% 100.0% 0.0% 100.0% 90.0% 0.0% 90.0% 100.0% 0.0% 100.0% 91.5% 0.0% 91.5%

 Male genital system 96.0% 96.0% 0.0% 73.2% 73.2% 0.0% 73.8% 73.8% 0.0% 73.3% 73.3% 0.0% 98.6% 98.6% 0.0% 97.6% 97.6% 0.0%

 Prostate 95.7% 95.7% 0.0% 72.3% 72.3% 0.0% 71.4% 71.4% 0.0% 70.6% 70.6% 0.0% 98.6% 98.6% 0.0% 97.5% 97.5% 0.0%

 Testis 98.2% 98.2% 0.0% 87.7% 87.7% 0.0% 86.0% 86.0% 0.0% 95.2% 95.2% 0.0% 98.5% 98.5% 0.0% 99.6% 99.6% 0.0%

 Penis 100.0% 100.0% 0.0% 76.5% 76.5% 0.0% 80.0% 80.0% 0.0% - - 0.0% - - 0.0% 98.6% 98.6% 0.0%

 Other male genital organs - - 0.0% 100.0% 100.0% 0.0% 0.0% 0.0% 0.0% - - 0.0% 100.0% 100.0% 0.0% 98.3% 98.3% 0.0%

 Urinary system 98.3% 98.3% 98.3% 91.7% 92.2% 90.2% 91.7% 94.3% 81.4% 88.3% 88.8% 86.4% 99.5% 99.6% 99.3% 95.9% 96.7% 94.0%

 Urinary bladder 99.3% 99.2% 100.0% 94.5% 94.5% 94.3% 95.7% 96.2% 92.1% 88.7% 89.2% 86.8% 99.9% 100.0% 99.2% 98.7% 98.9% 98.2%

 Kidney and renal pelvis 94.4% 93.6% 95.7% 85.9% 85.8% 86.0% 82.0% 87.7% 72.3% 85.4% 85.7% 84.8% 98.6% 98.1% 99.4% 90.8% 92.0% 88.9%

 Ureter - - - 100.0% 100.0% 100.0% 100.0% 100.0% 0.0% 100.0% 100.0% - 100.0% 100.0% - 98.1% 99.0% 96.8%

 Other urinary organs - - - 92.6% 97.6% 81.1% 100.0% - - 80.0% 80.0% 0.0% 100.0% 100.0% 0.0% 98.8% 99.1% 97.9%

 Eye and orbit 80.0% 66.7% 100.0% 67.8% 66.7% 69.1% 83.3% 90.0% 75.0% 90.9% 85.7% 100.0% 97.8% 97.6% 97.9% 73.1% 73.4% 72.8%

 Brain and other 

 nervous system 80.0% 77.2% 83.1% 79.1% 80.8% 77.0% 83.0% 86.1% 78.2% 65.7% 66.1% 65.4% 94.7% 95.9% 93.2% 87.5% 89.7% 84.6%

 Brain 80.2% 76.5% 84.1% 78.9% 80.4% 77.1% 83.6% 85.3% 80.8% 62.3% 63.4% 61.2% 94.9% 96.0% 93.5% 87.6% 89.9% 84.6%

 Cranial nerves and other 

 nervous system 78.9% 81.8% 75.0% 81.9% 90.7% 74.5% 72.7% 100.0% 40.0% 85.4% 82.6% 88.0% 92.5% 94.3% 90.6% 84.9% 85.7% 84.1%

Table 1.2 continued
 MECC Monograph 11

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

 Endocrine system 100.0% 100.0% 100.0% 92.3% 91.0% 92.8% 91.8% 90.6% 92.2% 89.5% 82.7% 94.1% 99.7% 100.0% 99.6% 99.2% 98.7% 99.4%

 Thyroid 100.0% 100.0% 100.0% 93.8% 94.3% 93.6% 95.2% 97.8% 94.5% 92.9% 88.9% 94.5% 100.0% 100.0% 100.0% 99.5% 99.2% 99.6%

 Other endocrine 

 including thymus 100.0% 100.0% 100.0% 76.2% 75.2% 77.2% 66.7% 73.7% 54.5% 78.3% 75.0% 90.0% 97.7% 100.0% 95.3% 95.2% 96.0% 94.2%

 Lymphoma 98.3% 98.5% 98.2% 91.6% 91.7% 91.4% 92.2% 91.9% 92.6% 93.1% 93.8% 91.9% 99.0% 99.3% 98.6% 97.9% 97.9% 97.9%

 Hodgkin lymphoma 96.4% 94.6% 97.8% 92.9% 92.9% 92.9% 93.4% 91.9% 95.5% 99.1% 98.7% 100.0% 99.2% 99.5% 98.8% 99.2% 99.1% 99.4%

 Hodgkin - Nodal 97.5% 94.4% 100.0% 93.0% 93.0% 93.0% 93.8% 91.8% 96.9% 99.0% 98.6% 100.0% 99.2% 99.4% 98.8% 99.2% 99.1% 99.3%

 Hodgkin - Extranodal 75.0% - 66.7% 87.5% 90.0% 83.3% 75.0% - 66.7% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 98.6% 97.7% 100.0%

 Non-Hodgkin lymphoma 98.9% 99.4% 98.3% 91.3% 91.5% 91.2% 91.8% 91.9% 91.6% 91.9% 92.7% 90.7% 98.9% 99.2% 98.4% 97.7% 97.7% 97.7%

 NHL - Nodal 99.0% 99.1% 98.7% 89.9% 89.7% 90.0% 90.4% 90.7% 89.9% 89.7% 91.0% 87.7% 98.7% 99.2% 97.9% 97.3% 97.5% 97.0%

 NHL - Extranodal 98.8% 100.0% 97.5% 96.6% 97.0% 96.0% 96.3% 96.2% 96.3% 99.2% 98.6% 100.0% 99.6% 99.4% 100.0% 98.4% 98.0% 98.9%

Myeloma 98.3% 97.0% 100.0% 73.5% 74.8% 71.9% 70.7% 73.3% 68.1% 100.0% 100.0% 100.0% 99.3% 100.0% 98.4% 91.4% 93.1% 89.4%

 Leukemia 99.1% 99.3% 98.9% 69.1% 71.5% 66.1% 70.2% 75.5% 62.4% 85.4% 85.5% 85.3% 99.7% 99.6% 99.8% 93.7% 94.7% 92.3%

 Lymphocytic leukemia 99.2% 98.7% 100.0% 70.8% 74.0% 66.3% 75.2% 83.3% 61.2% 100.0% 100.0% 100.0% 99.8% 99.8% 100.0% 94.4% 95.5% 92.8%

 Acute lymphocytic 

 leukemia 97.9% 96.4% 100.0% 75.5% 80.3% 68.7% 74.0% 82.0% 59.3% 100.0% 100.0% 100.0% 99.8% 99.7% 100.0% 98.4% 98.4% 98.3%

 Chronic lymphocytic 

 leukemia 100.0% 100.0% 100.0% 68.2% 70.6% 65.2% 76.1% 88.0% 61.9% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 92.2% 93.9% 89.7%

 Other lymphocytic 

 leukemia 100.0% 100.0% - 81.8% 83.9% 75.0% 80.0% 77.8% - 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 97.1% 98.0% 95.3%

 Myeloid and 

 monocytic 

 leukemia 98.9% 100.0% 97.5% 71.5% 72.5% 70.4% 70.4% 70.8% 69.8% 99.5% 100.0% 99.1% 99.8% 100.0% 99.6% 96.0% 96.6% 95.2%

 Acute myeloid 

 leukemia 98.3% 100.0% 96.0% 70.6% 70.8% 70.4% 64.7% 63.5% 66.7% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 96.3% 97.0% 95.4%

 Acute monocytic 

 leukemia - - 0.0% 67.9% 72.2% 60.0% 100.0% 100.0% - - 0.0% - 100.0% 100.0% 100.0% 98.6% 98.3% 99.2%

 Chronic myeloid 

 leukemia 100.0% 100.0% 100.0% 75.5% 76.8% 73.8% 80.0% 86.4% 73.9% 99.0% 100.0% 98.3% 99.5% 100.0% 99.0% 95.2% 95.7% 94.4%

 Other myeloid/ 

 monocytic leukemia 100.0% 100.0% - 62.8% 72.2% 56.0% - - 0.0% - - - 100.0% 100.0% 100.0% 93.7% 93.8% 93.5%

 Other leukemia 100.0% 100.0% 0.0% 46.4% 49.0% 43.2% 52.5% 63.2% 42.9% 21.3% 28.1% 10.8% 98.6% 97.8% 100.0% 70.6% 72.2% 68.9%

 Other acute leukemia 100.0% 100.0% 0.0% 52.8% 54.2% 50.7% 59.1% 60.0% 58.3% 68.8% 76.9% 33.3% 97.8% 96.7% 100.0% 79.9% 82.0% 78.0%

 Aleukemic, 

 subleukemic, and NOS‡ - - 0.0% 36.0% 38.8% 33.3% 44.4% 66.7% 22.2% 11.5% 13.6% 8.8% 100.0% 100.0% 100.0% 61.6% 63.8% 59.1%

 Miscellaneous 87.1% 87.1% 87.1% 69.8% 72.0% 67.8% 76.4% 82.0% 68.8% 57.5% 59.6% 54.7% 94.4% 94.3% 94.4% 77.5% 79.9% 75.3%

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡NOS indicates “not otherwise specified.”

Table 1.2 continued
12 MECC Monograph 

Overview and Summary Data Chapter 1

The annual age-standardized incidence rate (ASR) combines these 

age-specific rates into one summary measure, providing a simpler 

method of comparing the incidence rates in different populations 

while adjusting for differences in the age distributions. The 2 main 

methods for calculating the ASR are the direct and the indirect

method. This monograph follows the tradition established by the 

Cancer Incidence in Five Continents publications and uses the 

direct method. In order to calculate the ASR, one needs to define a 

standard population age distribution to which the other populations 

are referred. The standard population age distribution chosen for this 

monograph is known as the World Standard, and is shown in Table 

1.3. 

Also shown in Table 1.3 is a sample calculation of the ASR using 

data on female breast cancer from the Jordan cancer registry. 

Although the ASR is a very useful summary measure, it does have 

limitations. For example, a population with an unusually high rate 

of breast cancer in pre-menopausal women, but a moderate postmenopausal rate, will not usually display a high ASR because postmenopausal rates tend to dominate the value of the age-standardized 

rate. Therefore, examination of both age-standardized and agespecific rates is advised. 

As shown earlier, the MECC registry populations (aside from US 

SEER) are not very large; consequently, the numbers of cancer 

cases also are not very large. After subdivision into type of cancer 

and sex, the numbers of cases in each 5-year age group are in many 

cases small. Therefore, for each type of cancer, MECC has chosen 

age groups broader than 5 years to present the age-specific incidence 

rates. However, when choosing a wider range – e.g., 0-30 years – the 

problem of age distribution differences between the populations reemerges. Therefore, the direct age-standardization method has been 

applied to these broader age groups as well, to ensure comparability 

of rates across the populations. This method is illustrated in Table 

1.4. Although the resulting rates are thus also “age-standardized,” 

they are called age-specific rates in this monograph because they 

refer to the incidence rates in a particular age interval. 

ASRs are presented throughout this monograph as annual rates per 

100,000 persons, with one exception: In Chapter 15, childhood 

cancer annual rates are per million, to conform to most other 

publications on childhood cancer incidence rates. 

To caution against drawing strong conclusions on the basis of small 

numbers, MECC adopted the following conventions for tables of 

rates or percentages: Rates or percentages based on 0 or 3-15 cases 

Table 1.3. Overview and Summary Data: Sample Calculation of AgeStandardized Incidence Rate* in Jordan, Using the Standard World 

Distribution

Age (y) World Population

Jordan Breast Cancer 

Incidence Rate per 

100,000 Women

Expected Cases in 

World Population

X Wx Rx Ex=WxRx/105

0-4 y 120,000 0 0

5-9 y 100,000 0 0

10-14 y 90,000 0 0

15-19 y 90,000 0.1 0.1

20-24 y 80,000 0.8 0.6

25-29 y 80,000 5.7 4.6

30-34 y 60,000 20.8 12.5

35-39 y 60,000 47.1 28.3

40-44 y 60,000 73.6 44.2

45-49 y 60,000 82.6 49.6

50-54 y 50,000 129.3 64.6

55-59 y 40,000 114.6 45.8

60-64 y 40,000 134.8 53.9

65-69 y 30,000 131.1 39.3

70-74 y 20,000 103.0 20.6

75+ y 20,000 77.6 15.5

All ages 1,000,000 21.2 379.6

*Age-standardized rate = ∑ Ex / ∑ Wx = 379.6/ 1,000,000 = 38.0 per 100,000.
 MECC Monograph 13

Overview and Summary Data Chapter 1

Table 1.4. Overview and Summary Data: Calculation of Age-Standardized 

Incidence Rates for Selected Age Ranges, Using the Standard World 

Distribution

Age World 

Population

Jordan Breast Cancer 

Incidence Rate per 

100,000

Expected Cases in 

World Population

Age-Standardized 

Rate in the Age Range

X Wx Rx Ex=WxRx/105 Ex/(Wx/105)

0-4 y 120,000 0.0 0.0

5-9 y 100,000 0.0 0.0

10-14 y 90,000 0.0 0.0

15-19 y 90,000 0.1 0.1

20-24 y 80,000 0.8 0.6

25-29 y 80,000 5.7 4.6

30-34 y 60,000 20.8 12.5

35-39 y 60,000 47.1 28.3

0-39 y 680,000* - 47.1* 6.9

40-44 y 60,000 73.6 44.2

45-49 y 60,000 82.6 49.6

40-49 y 120,000* - 93.8* 78.2

50-54 y 50,000 129.3 64.6

55-59 y 40,000 114.6 45.8

50-59 y 90,000* - 110.4* 122.7

60-64 y 40,000 134.8 53.9

65-69 y 30,000 131.1 39.3

60-69 y 70,000* 93.2* 133.1

70-74 y 20,000 103.0 20.6

75+ y 20,000 77.6 15.5

70+ y 40,000* - 36.1* 90.2

* Obtained by summing over the 5-year age groups within the given age range. 

are italicized, and those based on 1-2 cases are omitted (indicated by 

a hyphen).

The standard error of an ASR is an expression of the uncertainty 

of the estimated rate due to sampling variation. It is calculated 

assuming that the number of cases diagnosed in each year has a 

Poisson distribution. The standard errors given in this monograph 

were calculated using the SEER*Stat package (http://seer.cancer.

gov/seerstat/) [2]. 

SUMMARY TABLES

Table 1.5 displays the numbers of cases registered at each registry 

over the period covered. Note that the numbers are particularly 

influenced by the length of the reporting period for each registry. 

To obtain average annual numbers of cases, the reader is required 

to divide the numbers for Israel and Jordan by 6, the numbers for 

Cyprus by 4, and the numbers for Egypt and SEER by 3.

The average annual total numbers of cases in the MECC populations 

were approximately: US SEER, 325,000; Israeli Jews, 17,500; 

Egyptians, 3,500; Jordanians, 3,000; Cypriots, 1,500; and Israeli 

Arabs, 1,000. These numbers are influenced principally by the size 

of the populations (see Table 1.1). Age distribution is also a strong 

factor. Thus, although the Cypriot population is fewer in number 

than the Israeli Arab population, it had more cases of cancer, mainly 

because it is an older population. 

Table 1.6 shows the proportions of all cancer cases that are due to 

a particular cancer type. This is useful for gaining impressions of 

the distribution of cancers in different populations, but cannot be 

used for comparing incidence rates. The table shows similarities and 

differences. Cancer of the digestive system accounted for about 20% 

of all cancers; and cancer of the breast, about 33% of female cancers 

– with relatively little variation across the populations. However, 

cancer of the male genital system (mostly prostate) accounted for 

as little as 4% of male cancers in Egypt, compared with 33% in US 

SEER. As might be expected, the younger populations (Israeli Arabs, 

Jordanians, and Egyptians) had a greater proportion of leukemias 

and lymphomas than the older populations (Cypriots, Israeli Jews, 

and US SEER). 
14 MECC Monograph 

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER*

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

All Sites 6,152 3,139 3,013 104,913 49,952 54,961 5,961 3,210 2,751 10,455 5,284 5,171 18,261 9,242 9,019 501,182 257,009 244,173

 Oral cavity and pharynx 91 56 35 2,116 1,179 937 143 95 48 391 219 172 441 287 154 11,194 7,447 3,747

 Lip 8 7 1 904 481 423 43 28 15 5 3 2 58 44 14 975 751 224

 Tongue 19 11 8 265 133 132 11 8 3 62 38 24 55 34 21 2,773 1,828 945

 Salivary gland 18 7 11 299 168 131 22 13 9 56 28 28 75 38 37 1,300 743 557

 Floor of mouth 4 4 0 33 21 12 2 2 0 3 2 1 14 9 5 774 523 251

 Gum and other mouth 18 11 7 242 123 119 20 13 7 82 38 44 39 26 13 1,788 941 847

 Nasopharynx 12 7 5 223 152 71 31 22 9 72 50 22 169 118 51 759 508 251

 Tonsil 4 3 1 33 24 9 3 3 0 11 5 6 10 4 6 1,412 1,113 299

 Oropharynx 2 2 0 43 25 18 3 1 2 4 1 3 5 4 1 339 244 95

 Hypopharynx 3 2 1 48 35 13 5 3 2 84 47 37 14 9 5 807 614 193

 Other oral cavity 

 and pharynx 3 2 1 26 17 9 3 2 1 12 7 5 2 1 1 267 182 85

 Digestive system 1,224 661 563 24,992 12,886 12,106 1,053 591 462 2,036 1,358 678 3,356 1,868 1,488 95,525 50,563 44,962

 Esophagus 23 19 4 665 390 275 20 14 6 94 58 36 144 99 45 4,826 3,616 1,210

 Stomach 198 112 86 3,605 2,169 1,436 177 108 69 206 126 80 687 434 253 9,235 5,541 3,694

 Small Intestine 12 10 2 288 169 119 26 15 11 28 16 12 86 56 30 1,823 954 869

 Colon and rectum 697 355 342 15,533 7,805 7,728 550 287 263 455 261 194 1,654 845 809 55,480 27,892 27,588

 Colon excluding rectum 475 237 238 11,463 5,627 5,836 357 175 182 300 174 126 1,061 546 515 40,008 19,161 20,847

 Cecum 73 34 39 1,179 542 637 24 13 11 25 14 11 41 22 19 9,260 3,995 5,265

 Appendix 6 5 1 60 21 39 4 2 2 2 0 2 8 5 3 531 249 282

 Ascending colon 28 12 16 1,795 871 924 60 32 28 17 11 6 44 27 17 6,603 2,971 3,632

 Hepatic flexure 9 4 5 327 148 179 11 4 7 16 13 3 16 10 6 2,284 1,088 1,196

 Transverse colon 18 10 8 607 297 310 15 6 9 21 11 10 49 24 25 3,682 1,670 2,012

 Splenic flexure 10 5 5 313 154 159 7 3 4 10 5 5 20 10 10 1,477 793 684

 Descending colon 20 12 8 922 459 463 26 16 10 23 14 9 30 16 14 2,345 1,217 1,128

 Sigmoid colon 155 75 80 3,350 1,713 1,637 110 51 59 51 31 20 253 111 142 11,831 6,256 5,575

 Colon, NOS† 156 80 76 2,910 1,422 1,488 100 48 52 135 75 60 600 321 279 1,995 922 1,073

 Rectum and junction 222 118 104 4,070 2,178 1,892 193 112 81 155 87 68 593 299 294 15,472 8,731 6,741

 Rectosigmoid junction 46 28 18 977 546 431 39 22 17 45 29 16 161 87 74 4,543 2,487 2,056

 Rectum 176 90 86 3,093 1,632 1,461 154 90 64 110 58 52 432 212 220 10,929 6,244 4,685

 Anus, anal canal, 

 and anorectum 8 4 4 224 112 112 8 5 3 31 15 16 52 36 16 1,487 643 844

 Liver and intrahepatic 

 bile duct 69 52 17 900 525 375 64 48 16 848 671 177 233 143 90 6,581 4,463 2,118

 Liver 60 44 16 801 479 322 62 47 15 830 655 175 205 132 73 5,736 4,013 1,723

 Intrahepatic bile duct 9 8 1 99 46 53 2 1 1 18 16 2 28 11 17 845 450 395

 Gallbladder 84 32 52 363 70 293 39 8 31 16 8 8 182 55 127 1,281 330 951

 Other biliary 9 5 4 325 163 162 31 19 12 51 29 22 49 30 19 1,665 878 787

 Pancreas 114 70 44 2,658 1,306 1,352 113 77 36 205 120 85 197 127 70 11,440 5,647 5,793

 Retroperitoneum 3 1 2 129 66 63 8 3 5 34 15 19 35 22 13 466 248 218

Table 1.5. Overview and Summary Data: Number of Cases, by Site and Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001
 MECC Monograph 15

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER*

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

 Peritoneum, omentum, 

 and mesentery 6 0 6 176 43 133 6 1 5 3 0 3 31 15 16 723 101 622

 Other digestive organs 1 1 0 126 68 58 11 6 5 65 39 26 6 6 0 518 250 268

 Respiratory system 600 493 107 8,797 5,966 2,831 855 738 117 706 537 169 1,797 1,518 279 69,363 39,393 29,970

 Nose, nasal cavity, 

 and middle ear 9 6 3 133 74 59 10 6 4 30 13 17 42 22 20 712 399 313

 Larynx 59 53 6 886 756 130 112 103 9 145 133 12 365 335 30 3,927 3,107 820

 Lung and bronchus 514 423 91 7,402 4,892 2,510 706 611 95 496 370 126 1,336 1,128 208 63,559 34,973 28,586

 Pleura 8 6 2 188 120 68 11 7 4 23 14 9 33 19 14 949 762 187

Trachea, mediastinum, and 

other respiratory organs 10 5 5 188 124 64 16 11 5 12 7 5 21 14 7 216 152 64

 Bones and joints 41 28 13 403 235 168 44 25 19 156 88 68 287 171 116 955 534 421

 Soft tissue including heart 43 24 19 910 510 400 102 57 45 236 117 119 228 131 97 3,236 1,830 1,406

 Skin excluding 

 basal and squamous 110 49 61 4,808 2,578 2,230 91 53 38 49 31 18 175 108 67 22,112 12,761 9,351

 Melanoma of the skin 95 40 55 3,698 1,845 1,853 44 26 18 22 11 11 87 46 41 19,235 10,810 8,425

 Other non-epithelial skin 15 9 6 1,110 733 377 47 27 20 27 20 7 88 62 26 2,877 1,951 926

 Breast 1,076 10 1,066 17,528 203 17,325 773 11 762 1,971 26 1,945 2,975 45 2,930 79,368 566 78,802

 Female genital system 469 0 469 5,783 0 5,783 305 0 305 470 0 470 1,028 0 1,028 29,838 0 29,838

 Cervix uteri 70 0 70 922 0 922 54 0 54 96 0 96 194 0 194 5,284 0 5,284

 Corpus and uterus, NOS† 225 0 225 2,645 0 2,645 161 0 161 124 0 124 405 0 405 14,129 0 14,129

 Corpus uteri 218 0 218 2,227 0 2,227 138 0 138 54 0 54 217 0 217 13,849 0 13,849

 Uterus, NOS† 7 0 7 418 0 418 23 0 23 70 0 70 188 0 188 280 0 280

 Ovary 143 0 143 1,749 0 1,749 75 0 75 210 0 210 372 0 372 8,233 0 8,233

 Vagina 6 0 6 86 0 86 5 0 5 6 0 6 14 0 14 419 0 419

 Vulva 25 0 25 254 0 254 6 0 6 24 0 24 23 0 23 1,351 0 1,351

 Other female 

 genital organs 0 0 0 127 0 127 4 0 4 10 0 10 20 0 20 422 0 422

 Male genital system 799 799 0 9,321 9,321 0 324 324 0 217 217 0 896 896 0 84,094 84,094 0

 Prostate 727 727 0 8,735 8,735 0 269 269 0 194 194 0 693 693 0 80,331 80,331 0

 Testis 55 55 0 554 554 0 50 50 0 21 21 0 194 194 0 3,224 3,224 0

 Penis 15 15 0 17 17 0 5 5 0 1 1 0 1 1 0 367 367 0

 Other male genital organs 2 2 0 15 15 0 0 0 0 1 1 0 8 8 0 172 172 0

 Urinary system 588 467 121 9,596 7,114 2,482 434 348 86 1,239 967 272 1,467 1,187 280 34,619 24,080 10,539

 Urinary bladder 460 387 73 6,215 4,991 1,224 299 261 38 1,057 852 205 1,038 915 123 21,355 15,893 5,462

 Kidney and renal pelvis 124 78 46 3,152 1,967 1,185 128 81 47 171 105 66 418 262 156 12,409 7,650 4,759

 Ureter 2 1 1 108 72 36 4 4 0 6 5 1 8 7 1 529 308 221

 Other urinary organs 2 1 1 121 84 37 3 2 1 5 5 0 3 3 0 326 229 97

 Eye and orbit 10 6 4 143 75 68 18 10 8 22 14 8 89 41 48 811 447 364

Table 1.5 continued
16 MECC Monograph 

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER*

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

 Brain and other 

 nervous system 150 79 71 1,690 939 751 200 122 78 324 165 159 875 506 369 7,060 3,964 3,096

 Brain 131 68 63 1,596 896 700 189 116 73 276 142 134 808 471 337 6,611 3,761 2,850

 Cranial nerves and other 

 nervous system 19 11 8 94 43 51 11 6 5 48 23 25 67 35 32 449 203 246

 Endocrine system 189 44 145 2,618 659 1,959 257 64 193 200 81 119 705 217 488 9,371 2,527 6,844

 Thyroid 179 40 139 2,404 546 1,858 227 45 182 154 45 109 617 172 445 8,684 2,152 6,532

 Other endocrine 

 including thymus 10 4 6 214 113 101 30 19 11 46 36 10 88 45 43 687 375 312

 Lymphoma 357 194 163 6,638 3,371 3,267 615 346 269 1,316 820 496 1,733 1,042 691 23,698 12,913 10,785

 Hodgkin lymphoma 83 37 46 1,030 521 509 166 99 67 218 151 67 639 383 256 3,099 1,706 1,393

 Hodgkin - Nodal 79 36 43 1,014 511 503 162 98 64 210 147 63 605 359 246 3,027 1,663 1,364

 Hodgkin - Extranodal 4 1 3 16 10 6 4 1 3 8 4 4 34 24 10 72 43 29

 Non-Hodgkin lymphoma 274 157 117 5,608 2,850 2,758 449 247 202 1,098 669 429 1,094 659 435 20,599 11,207 9,392

 NHL - Nodal 191 114 77 4,385 2,155 2,230 342 194 148 848 523 325 829 496 333 13,712 7,494 6,218

 NHL - Extranodal 83 43 40 1,223 695 528 107 53 54 250 146 104 265 163 102 6,887 3,713 3,174

Myeloma 58 33 25 1,338 711 627 92 45 47 68 47 21 268 143 125 5,849 3,125 2,724

 Leukemia 223 134 89 3,220 1,790 1,430 325 192 133 515 283 232 1,354 782 572 13,178 7,528 5,650

 Lymphocytic leukemia 127 78 49 1,728 1,001 727 133 84 49 218 131 87 662 403 259 5,981 3,570 2,411

 Acute lymphocytic 

 leukemia 48 28 20 322 188 134 77 50 27 122 69 53 486 294 192 1,721 945 776

 Chronic lymphocytic 

 leukemia 68 41 27 1,252 695 557 46 25 21 87 56 31 144 89 55 3,769 2,283 1,486

 Other lymphocytic 

 leukemia 11 9 2 154 118 36 10 9 1 9 6 3 32 20 12 491 342 149

Myeloid and monocytic 

leukemia 92 52 40 1,229 644 585 152 89 63 203 95 108 553 290 263 6,382 3,545 2,837

 Acute myeloid 

 leukemia 60 35 25 840 431 409 102 63 39 98 52 46 308 169 139 4,139 2,242 1,897

 Acute monocytic 

 leukemia 1 1 0 28 18 10 4 3 1 2 0 2 29 15 14 290 172 118

 Chronic myeloid 

 leukemia 26 12 14 318 177 141 45 22 23 101 42 59 194 95 99 1,795 1,050 745

 Other myeloid/ 

 monocytic leukemia 5 4 1 43 18 25 1 1 0 2 1 1 22 11 11 158 81 77

 Other leukemia 4 4 0 263 145 118 40 19 21 94 57 37 139 89 50 815 413 402

 Other acute leukemia 3 3 0 163 96 67 22 10 12 16 13 3 92 60 32 398 189 209

Aleukemic, subleukemic, and 

NOS† 1 1 0 100 49 51 18 9 9 78 44 34 47 29 18 417 224 193

 Miscellaneous 124 62 62 5,012 2,415 2,597 330 189 141 539 314 225 587 300 287 10,911 5,237 5,674

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

†NOS indicates “not otherwise specified.”

Table 1.5 continued
 MECC Monograph 17

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 6,152 3,139 3,013 104,913 49,952 54,961 5,961 3,210 2,751 10,455 5,284 5,171 18,261 9,242 9,019 501,182 257,009 244,173

 Oral cavity and pharynx 1.5% 1.8% 1.2% 2.0% 2.4% 1.7% 2.4% 3.0% 1.7% 3.7% 4.1% 3.3% 2.4% 3.1% 1.7% 2.2% 2.9% 1.5%

 Lip 0.1% 0.2% - 0.9% 1.0% 0.8% 0.7% 0.9% 0.5% 0.0% 0.1% - 0.3% 0.5% 0.2% 0.2% 0.3% 0.1%

 Tongue 0.3% 0.4% 0.3% 0.3% 0.3% 0.2% 0.2% 0.3% 0.1% 0.6% 0.7% 0.5% 0.3% 0.4% 0.2% 0.6% 0.7% 0.4%

 Salivary gland 0.3% 0.2% 0.4% 0.3% 0.3% 0.2% 0.4% 0.4% 0.3% 0.5% 0.5% 0.5% 0.4% 0.4% 0.4% 0.3% 0.3% 0.2%

 Floor of mouth 0.1% 0.1% 0.0% 0.0% 0.0% 0.0% - - 0.0% 0.0% - - 0.1% 0.1% 0.1% 0.2% 0.2% 0.1%

 Gum and other mouth 0.3% 0.4% 0.2% 0.2% 0.2% 0.2% 0.3% 0.4% 0.3% 0.8% 0.7% 0.9% 0.2% 0.3% 0.1% 0.4% 0.4% 0.3%

 Nasopharynx 0.2% 0.2% 0.2% 0.2% 0.3% 0.1% 0.5% 0.7% 0.3% 0.7% 0.9% 0.4% 0.9% 1.3% 0.6% 0.2% 0.2% 0.1%

 Tonsil 0.1% 0.1% - 0.0% 0.0% 0.0% 0.1% 0.1% 0.0% 0.1% 0.1% 0.1% 0.1% 0.0% 0.1% 0.3% 0.4% 0.1%

 Oropharynx - - 0.0% 0.0% 0.1% 0.0% 0.1% - - 0.0% - 0.1% 0.0% 0.0% - 0.1% 0.1% 0.0%

 Hypopharynx 0.0% - - 0.0% 0.1% 0.0% 0.1% 0.1% - 0.8% 0.9% 0.7% 0.1% 0.1% 0.1% 0.2% 0.2% 0.1%

 Other oral cavity 

 and pharynx 0.0% - - 0.0% 0.0% 0.0% 0.1% - - 0.1% 0.1% 0.1% - - - 0.1% 0.1% 0.0%

 Digestive system 19.9% 21.1% 18.7% 23.8% 25.8% 22.0% 17.7% 18.4% 16.8% 19.5% 25.7% 13.1% 18.4% 20.2% 16.5% 19.1% 19.7% 18.4%

 Esophagus 0.4% 0.6% 0.1% 0.6% 0.8% 0.5% 0.3% 0.4% 0.2% 0.9% 1.1% 0.7% 0.8% 1.1% 0.5% 1.0% 1.4% 0.5%

 Stomach 3.2% 3.6% 2.9% 3.4% 4.3% 2.6% 3.0% 3.4% 2.5% 2.0% 2.4% 1.5% 3.8% 4.7% 2.8% 1.8% 2.2% 1.5%

 Small intestine 0.2% 0.3% - 0.3% 0.3% 0.2% 0.4% 0.5% 0.4% 0.3% 0.3% 0.2% 0.5% 0.6% 0.3% 0.4% 0.4% 0.4%

 Colon and rectum 11.3% 11.3% 11.4% 14.8% 15.6% 14.1% 9.2% 8.9% 9.6% 4.4% 4.9% 3.8% 9.1% 9.1% 9.0% 11.1% 10.9% 11.3%

 Colon excluding rectum 7.7% 7.6% 7.9% 10.9% 11.3% 10.6% 6.0% 5.5% 6.6% 2.9% 3.3% 2.4% 5.8% 5.9% 5.7% 8.0% 7.5% 8.5%

 Cecum 1.2% 1.1% 1.3% 1.1% 1.1% 1.2% 0.4% 0.4% 0.4% 0.2% 0.3% 0.2% 0.2% 0.2% 0.2% 1.8% 1.6% 2.2%

 Appendix 0.1% 0.2% - 0.1% 0.0% 0.1% 0.1% - - - 0.0% - 0.0% 0.1% 0.0% 0.1% 0.1% 0.1%

 Ascending colon 0.5% 0.4% 0.5% 1.7% 1.7% 1.7% 1.0% 1.0% 1.0% 0.2% 0.2% 0.1% 0.2% 0.3% 0.2% 1.3% 1.2% 1.5%

 Hepatic flexure 0.1% 0.1% 0.2% 0.3% 0.3% 0.3% 0.2% 0.1% 0.3% 0.2% 0.2% 0.1% 0.1% 0.1% 0.1% 0.5% 0.4% 0.5%

 Transverse colon 0.3% 0.3% 0.3% 0.6% 0.6% 0.6% 0.3% 0.2% 0.3% 0.2% 0.2% 0.2% 0.3% 0.3% 0.3% 0.7% 0.7% 0.8%

 Splenic flexure 0.2% 0.2% 0.2% 0.3% 0.3% 0.3% 0.1% 0.1% 0.1% 0.1% 0.1% 0.1% 0.1% 0.1% 0.1% 0.3% 0.3% 0.3%

 Descending colon 0.3% 0.4% 0.3% 0.9% 0.9% 0.8% 0.4% 0.5% 0.4% 0.2% 0.3% 0.2% 0.2% 0.2% 0.2% 0.5% 0.5% 0.5%

 Sigmoid colon 2.5% 2.4% 2.7% 3.2% 3.4% 3.0% 1.8% 1.6% 2.1% 0.5% 0.6% 0.4% 1.4% 1.2% 1.6% 2.4% 2.4% 2.3%

 Colon, NOS‡ 2.5% 2.5% 2.5% 2.8% 2.8% 2.7% 1.7% 1.5% 1.9% 1.3% 1.4% 1.2% 3.3% 3.5% 3.1% 0.4% 0.4% 0.4%

 Rectum and junction 3.6% 3.8% 3.5% 3.9% 4.4% 3.4% 3.2% 3.5% 2.9% 1.5% 1.6% 1.3% 3.2% 3.2% 3.3% 3.1% 3.4% 2.8%

 Rectosigmoid junction 0.7% 0.9% 0.6% 0.9% 1.1% 0.8% 0.7% 0.7% 0.6% 0.4% 0.5% 0.3% 0.9% 0.9% 0.8% 0.9% 1.0% 0.8%

 Rectum 2.9% 2.9% 2.9% 2.9% 3.3% 2.7% 2.6% 2.8% 2.3% 1.1% 1.1% 1.0% 2.4% 2.3% 2.4% 2.2% 2.4% 1.9%

 Anus, anal canal, 

 and anorectum 0.1% 0.1% 0.1% 0.2% 0.2% 0.2% 0.1% 0.2% 0.1% 0.3% 0.3% 0.3% 0.3% 0.4% 0.2% 0.3% 0.3% 0.3%

 Liver and intrahepatic 

 bile duct 1.1% 1.7% 0.6% 0.9% 1.1% 0.7% 1.1% 1.5% 0.6% 8.1% 12.7% 3.4% 1.3% 1.5% 1.0% 1.3% 1.7% 0.9%

 Liver 1.0% 1.4% 0.5% 0.8% 1.0% 0.6% 1.0% 1.5% 0.5% 7.9% 12.4% 3.4% 1.1% 1.4% 0.8% 1.1% 1.6% 0.7%

 Intrahepatic bile duct 0.1% 0.3% - 0.1% 0.1% 0.1% - - - 0.2% 0.3% - 0.2% 0.1% 0.2% 0.2% 0.2% 0.2%

 Gallbladder 1.4% 1.0% 1.7% 0.3% 0.1% 0.5% 0.7% 0.3% 1.1% 0.2% 0.2% 0.2% 1.0% 0.6% 1.4% 0.3% 0.1% 0.4%

 Other biliary 0.1% 0.2% 0.1% 0.3% 0.3% 0.3% 0.5% 0.6% 0.4% 0.5% 0.5% 0.4% 0.3% 0.3% 0.2% 0.3% 0.3% 0.3%

 Pancreas 1.9% 2.2% 1.5% 2.5% 2.6% 2.5% 1.9% 2.4% 1.3% 2.0% 2.3% 1.6% 1.1% 1.4% 0.8% 2.3% 2.2% 2.4%

 Retroperitoneum 0.0% - - 0.1% 0.1% 0.1% 0.1% 0.1% 0.2% 0.3% 0.3% 0.4% 0.2% 0.2% 0.1% 0.1% 0.1% 0.1%

 Peritoneum, omentum, 

 and mesentery 0.1% 0.0% 0.2% 0.2% 0.1% 0.2% 0.1% - 0.2% 0.0% 0.0% 0.1% 0.2% 0.2% 0.2% 0.1% 0.0% 0.3%

 Other digestive organs - - 0.0% 0.1% 0.1% 0.1% 0.2% 0.2% 0.2% 0.6% 0.7% 0.5% 0.0% 0.1% 0.0% 0.1% 0.1% 0.1%

Table 1.6. Overview and Summary Data: Number and Proportions of Cases, by Site and Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001*
18 MECC Monograph 

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

 Respiratory system 9.8% 15.7% 3.6% 8.4% 11.9% 5.2% 14.3% 23.0% 4.3% 6.8% 10.2% 3.3% 9.8% 16.4% 3.1% 13.8% 15.3% 12.3%

 Nose, nasal cavity, 

 and middle ear 0.1% 0.2% 0.1% 0.1% 0.1% 0.1% 0.2% 0.2% 0.1% 0.3% 0.2% 0.3% 0.2% 0.2% 0.2% 0.1% 0.2% 0.1%

 Larynx 1.0% 1.7% 0.2% 0.8% 1.5% 0.2% 1.9% 3.2% 0.3% 1.4% 2.5% 0.2% 2.0% 3.6% 0.3% 0.8% 1.2% 0.3%

 Lung and bronchus 8.4% 13.5% 3.0% 7.1% 9.8% 4.6% 11.8% 19.0% 3.5% 4.7% 7.0% 2.4% 7.3% 12.2% 2.3% 12.7% 13.6% 11.7%

 Pleura 0.1% 0.2% - 0.2% 0.2% 0.1% 0.2% 0.2% 0.1% 0.2% 0.3% 0.2% 0.2% 0.2% 0.2% 0.2% 0.3% 0.1%

Trachea, mediastinum, and 

other respiratory organs 0.2% 0.2% 0.2% 0.2% 0.2% 0.1% 0.3% 0.3% 0.2% 0.1% 0.1% 0.1% 0.1% 0.2% 0.1% 0.0% 0.1% 0.0%

 Bones and joints 0.7% 0.9% 0.4% 0.4% 0.5% 0.3% 0.7% 0.8% 0.7% 1.5% 1.7% 1.3% 1.6% 1.9% 1.3% 0.2% 0.2% 0.2%

 Soft tissue including heart 0.7% 0.8% 0.6% 0.9% 1.0% 0.7% 1.7% 1.8% 1.6% 2.3% 2.2% 2.3% 1.2% 1.4% 1.1% 0.6% 0.7% 0.6%

 Skin excluding 

 basal and squamous 1.8% 1.6% 2.0% 4.6% 5.2% 4.1% 1.5% 1.7% 1.4% 0.5% 0.6% 0.3% 1.0% 1.2% 0.7% 4.4% 5.0% 3.8%

 Melanoma of the skin 1.5% 1.3% 1.8% 3.5% 3.7% 3.4% 0.7% 0.8% 0.7% 0.2% 0.2% 0.2% 0.5% 0.5% 0.5% 3.8% 4.2% 3.5%

 Other non-epithelial skin 0.2% 0.3% 0.2% 1.1% 1.5% 0.7% 0.8% 0.8% 0.7% 0.3% 0.4% 0.1% 0.5% 0.7% 0.3% 0.6% 0.8% 0.4%

 Breast 17.5% 0.3% 35.4% 16.7% 0.4% 31.5% 13.0% 0.3% 27.7% 18.9% 0.5% 37.6% 16.3% 0.5% 32.5% 15.8% 0.2% 32.3%

 Female genital system 7.6% 0.0% 15.6% 5.5% 0.0% 10.5% 5.1% 0.0% 11.1% 4.5% 0.0% 9.1% 5.6% 0.0% 11.4% 6.0% 0.0% 12.2%

 Cervix uteri 1.1% 0.0% 2.3% 0.9% 0.0% 1.7% 0.9% 0.0% 2.0% 0.9% 0.0% 1.9% 1.1% 0.0% 2.2% 1.1% 0.0% 2.2%

 Corpus and uterus, NOS‡ 3.7% 0.0% 7.5% 2.5% 0.0% 4.8% 2.7% 0.0% 5.9% 1.2% 0.0% 2.4% 2.2% 0.0% 4.5% 2.8% 0.0% 5.8%

 Corpus uteri 3.5% 0.0% 7.2% 2.1% 0.0% 4.1% 2.3% 0.0% 5.0% 0.5% 0.0% 1.0% 1.2% 0.0% 2.4% 2.8% 0.0% 5.7%

 Uterus, NOS‡ 0.1% 0.0% 0.2% 0.4% 0.0% 0.8% 0.4% 0.0% 0.8% 0.7% 0.0% 1.4% 1.0% 0.0% 2.1% 0.1% 0.0% 0.1%

 Ovary 2.3% 0.0% 4.7% 1.7% 0.0% 3.2% 1.3% 0.0% 2.7% 2.0% 0.0% 4.1% 2.0% 0.0% 4.1% 1.6% 0.0% 3.4%

 Vagina 0.1% 0.0% 0.2% 0.1% 0.0% 0.2% 0.1% 0.0% 0.2% 0.1% 0.0% 0.1% 0.1% 0.0% 0.2% 0.1% 0.0% 0.2%

 Vulva 0.4% 0.0% 0.8% 0.2% 0.0% 0.5% 0.1% 0.0% 0.2% 0.2% 0.0% 0.5% 0.1% 0.0% 0.3% 0.3% 0.0% 0.6%

 Other female 

 genital organs 0.0% 0.0% 0.0% 0.1% 0.0% 0.2% 0.1% 0.0% 0.1% 0.1% 0.0% 0.2% 0.1% 0.0% 0.2% 0.1% 0.0% 0.2%

 Male genital system 13.0% 25.5% 0.0% 8.9% 18.7% 0.0% 5.4% 10.1% 0.0% 2.1% 4.1% 0.0% 4.9% 9.7% 0.0% 16.8% 32.7% 0.0%

 Prostate 11.8% 23.2% 0.0% 8.3% 17.5% 0.0% 4.5% 8.4% 0.0% 1.9% 3.7% 0.0% 3.8% 7.5% 0.0% 16.0% 31.3% 0.0%

 Testis 0.9% 1.8% 0.0% 0.5% 1.1% 0.0% 0.8% 1.6% 0.0% 0.2% 0.4% 0.0% 1.1% 2.1% 0.0% 0.6% 1.3% 0.0%

 Penis 0.2% 0.5% 0.0% 0.0% 0.0% 0.0% 0.1% 0.2% 0.0% - - 0.0% - - 0.0% 0.1% 0.1% 0.0%

 Other male genital organs - - 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% - - 0.0% 0.0% 0.1% 0.0% 0.0% 0.1% 0.0%

 Urinary system 9.6% 14.9% 4.0% 9.1% 14.2% 4.5% 7.3% 10.8% 3.1% 11.9% 18.3% 5.3% 8.0% 12.8% 3.1% 6.9% 9.4% 4.3%

 Urinary bladder 7.5% 12.3% 2.4% 5.9% 10.0% 2.2% 5.0% 8.1% 1.4% 10.1% 16.1% 4.0% 5.7% 9.9% 1.4% 4.3% 6.2% 2.2%

 Kidney and renal pelvis 2.0% 2.5% 1.5% 3.0% 3.9% 2.2% 2.1% 2.5% 1.7% 1.6% 2.0% 1.3% 2.3% 2.8% 1.7% 2.5% 3.0% 2.0%

 Ureter - - - 0.1% 0.1% 0.1% 0.1% 0.1% 0.0% 0.1% 0.1% - 0.0% 0.1% - 0.1% 0.1% 0.1%

 Other urinary organs - - - 0.1% 0.2% 0.1% 0.1% - - 0.0% 0.1% 0.0% 0.0% 0.0% 0.0% 0.1% 0.1% 0.0%

 Eye and orbit 0.2% 0.2% 0.1% 0.1% 0.2% 0.1% 0.3% 0.3% 0.3% 0.2% 0.3% 0.2% 0.5% 0.4% 0.5% 0.2% 0.2% 0.2%

 Brain and other 

 nervous system 2.4% 2.5% 2.4% 1.6% 1.9% 1.4% 3.4% 3.8% 2.8% 3.1% 3.1% 3.1% 4.8% 5.5% 4.1% 1.4% 1.5% 1.3%

 Brain 2.1% 2.2% 2.1% 1.5% 1.8% 1.3% 3.2% 3.6% 2.7% 2.6% 2.7% 2.6% 4.4% 5.1% 3.7% 1.3% 1.5% 1.2%

 Cranial nerves and other 

 nervous system 0.3% 0.4% 0.3% 0.1% 0.1% 0.1% 0.2% 0.2% 0.2% 0.5% 0.4% 0.5% 0.4% 0.4% 0.4% 0.1% 0.1% 0.1%

Table 1.6. continued
 MECC Monograph 19

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

 Endocrine system 3.1% 1.4% 4.8% 2.5% 1.3% 3.6% 4.3% 2.0% 7.0% 1.9% 1.5% 2.3% 3.9% 2.3% 5.4% 1.9% 1.0% 2.8%

 Thyroid 2.9% 1.3% 4.6% 2.3% 1.1% 3.4% 3.8% 1.4% 6.6% 1.5% 0.9% 2.1% 3.4% 1.9% 4.9% 1.7% 0.8% 2.7%

 Other endocrine 

 including thymus 0.2% 0.1% 0.2% 0.2% 0.2% 0.2% 0.5% 0.6% 0.4% 0.4% 0.7% 0.2% 0.5% 0.5% 0.5% 0.1% 0.1% 0.1%

 Lymphoma 5.8% 6.2% 5.4% 6.3% 6.7% 5.9% 10.3% 10.8% 9.8% 12.6% 15.5% 9.6% 9.5% 11.3% 7.7% 4.7% 5.0% 4.4%

 Hodgkin lymphoma 1.4% 1.2% 1.5% 1.0% 1.0% 0.9% 2.8% 3.1% 2.4% 2.1% 2.9% 1.3% 3.5% 4.1% 2.8% 0.6% 0.7% 0.6%

 Hodgkin - Nodal 1.3% 1.1% 1.4% 1.0% 1.0% 0.9% 2.7% 3.1% 2.3% 2.0% 2.8% 1.2% 3.3% 3.9% 2.7% 0.6% 0.6% 0.6%

 Hodgkin - Extranodal 0.1% - 0.1% 0.0% 0.0% 0.0% 0.1% - 0.1% 0.1% 0.1% 0.1% 0.2% 0.3% 0.1% 0.0% 0.0% 0.0%

 Non-Hodgkin lymphoma 4.5% 5.0% 3.9% 5.3% 5.7% 5.0% 7.5% 7.7% 7.3% 10.5% 12.7% 8.3% 6.0% 7.1% 4.8% 4.1% 4.4% 3.8%

 NHL - Nodal 3.1% 3.6% 2.6% 4.2% 4.3% 4.1% 5.7% 6.0% 5.4% 8.1% 9.9% 6.3% 4.5% 5.4% 3.7% 2.7% 2.9% 2.5%

 NHL - Extranodal 1.4% 1.4% 1.3% 1.2% 1.4% 1.0% 1.8% 1.7% 2.0% 2.4% 2.8% 2.0% 1.5% 1.8% 1.1% 1.4% 1.4% 1.3%

Myeloma 0.9% 1.1% 0.8% 1.3% 1.4% 1.1% 1.5% 1.4% 1.7% 0.7% 0.9% 0.4% 1.5% 1.5% 1.4% 1.2% 1.2% 1.1%

 Leukemia 3.6% 4.3% 3.0% 3.1% 3.6% 2.6% 5.5% 6.0% 4.8% 4.9% 5.4% 4.5% 7.4% 8.5% 6.3% 2.6% 2.9% 2.3%

 Lymphocytic leukemia 2.1% 2.5% 1.6% 1.6% 2.0% 1.3% 2.2% 2.6% 1.8% 2.1% 2.5% 1.7% 3.6% 4.4% 2.9% 1.2% 1.4% 1.0%

 Acute lymphocytic 

 leukemia 0.8% 0.9% 0.7% 0.3% 0.4% 0.2% 1.3% 1.6% 1.0% 1.2% 1.3% 1.0% 2.7% 3.2% 2.1% 0.3% 0.4% 0.3%

 Chronic lymphocytic 

 leukemia 1.1% 1.3% 0.9% 1.2% 1.4% 1.0% 0.8% 0.8% 0.8% 0.8% 1.1% 0.6% 0.8% 1.0% 0.6% 0.8% 0.9% 0.6%

 Other lymphocytic 

 leukemia 0.2% 0.3% - 0.1% 0.2% 0.1% 0.2% 0.3% - 0.1% 0.1% 0.1% 0.2% 0.2% 0.1% 0.1% 0.1% 0.1%

Myeloid and monocytic 

leukemia 1.5% 1.7% 1.3% 1.2% 1.3% 1.1% 2.6% 2.8% 2.3% 1.9% 1.8% 2.1% 3.0% 3.1% 2.9% 1.3% 1.4% 1.2%

 Acute myeloid 

 Leukemia 1.0% 1.1% 0.8% 0.8% 0.9% 0.7% 1.7% 2.0% 1.4% 0.9% 1.0% 0.9% 1.7% 1.8% 1.5% 0.8% 0.9% 0.8%

 Acute monocytic 

 leukemia - - 0.0% 0.0% 0.0% 0.0% 0.1% 0.1% - - 0.0% - 0.2% 0.2% 0.2% 0.1% 0.1% 0.0%

 Chronic myeloid 

 leukemia 0.4% 0.4% 0.5% 0.3% 0.4% 0.3% 0.8% 0.7% 0.8% 1.0% 0.8% 1.1% 1.1% 1.0% 1.1% 0.4% 0.4% 0.3%

 Other myeloid/ 

 monocytic leukemia 0.1% 0.1% - 0.0% 0.0% 0.0% - - 0.0% - - - 0.1% 0.1% 0.1% 0.0% 0.0% 0.0%

 Other leukemia 0.1% 0.1% 0.0% 0.3% 0.3% 0.2% 0.7% 0.6% 0.8% 0.9% 1.1% 0.7% 0.8% 1.0% 0.6% 0.2% 0.2% 0.2%

 Other acute leukemia 0.0% 0.1% 0.0% 0.2% 0.2% 0.1% 0.4% 0.3% 0.4% 0.2% 0.2% 0.1% 0.5% 0.7% 0.4% 0.1% 0.1% 0.1%

Aleukemic, Subleukemic, and 

NOS‡ - - 0.0% 0.1% 0.1% 0.1% 0.3% 0.3% 0.3% 0.7% 0.8% 0.7% 0.3% 0.3% 0.2% 0.1% 0.1% 0.1%

 Miscellaneous 2.0% 2.0% 2.1% 4.8% 4.8% 4.7% 5.5% 5.9% 5.1% 5.2% 5.9% 4.4% 3.2% 3.2% 3.2% 2.2% 2.0% 2.3%

*The symbols “-” = 1-2 cases; “[numeral]” (italics) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡NOS indicates “not otherwise specified.”

Table 1.6. continued
20 MECC Monograph 

Overview and Summary Data Chapter 1

Table 1.7 shows the ASRs for different cancer types. Two 

populations, US SEER (318.6) and Israeli Jews (274.4), had 

substantially higher rates overall, compared with the others. 

The Cypriot (164.2), Israeli Arab (149.8), and Egyptian (143.0) 

populations had intermediate rates, while the Jordanian rates (113.3) 

were the lowest. This same pattern is seen for both males and 

females. 

Comparison of the ASRs across populations for different cancers 

does not always conform to the overall pattern seen for “all sites.” 

The results for specific sites and types of cancer are reviewed in 

detail in the remainder of this monograph. 

Table 1.8 presents the standard errors of the estimated rates that are 

shown in Table 1.7. These standard errors may be used to judge the 

limits of uncertainty in an estimated rate. For example, Table 1.7 

shows that the ASR of cancer of the oral cavity and pharynx among 

females in Cyprus is 1.9, and Table 1.8 shows that its standard error 

is 0.3. Approximate 95% confidence limits for this rate are therefore 

given by 1.9 ± 2x0.3 = (1.3, 2.5). In other words, the true rate is very 

likely to lie between 1.3 and 2.5. As the numbers of cases underlying 

the estimated rate increase, the standard error becomes smaller 

relative to the rate. Thus the ASR of breast cancer among Israeli 

Jewish females is 93.1, and its standard error is 0.7 (less than 1% of 

the estimate), so that the 95% confidence limits are approximately 

(91.7, 94.5), meaning that the rate is quite precisely estimated. 

The main source of the data presented in the following chapters is 

the MECC Joint Cancer Registration Project. Other sources that 

are used for comparative purposes are Cancer Incidence in Five 

Continents [3] and GLOBOCAN [4]. The data from the former 

publication are derived from well-established population-based 

registries and include a wide range of countries, but are not available 

for all the world’s populations. Data from the latter publication are 

based on a variety of sources, including population-based registries, 

hospital-based registries, and population-based mortality records. 

Although GLOBOCAN’s data provide wider coverage than Cancer 

Incidence in Five Continents, they are necessarily less reliable than 

data based on population-based registry data alone.
 MECC Monograph 21

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER‡

 1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

All Sites 164.2 173.3 159.4 274.4 282.6 272.1 149.8 175.7 128.7 143.0 152.6 135.0 113.3 115.2 112.2 318.6 363.8 285.9

 Oral cavity and pharynx 2.5 3.1 1.9 5.5 6.9 4.3 3.5 4.8 2.3 5.5 6.4 4.6 2.7 3.5 1.8 7.4 10.9 4.3

 Lip 0.2 0.4 - 2.3 2.7 2.0 1.1 1.5 0.7 0.1 0.1 - 0.4 0.6 0.2 0.6 1.0 0.2

 Tongue 0.5 0.6 0.4 0.7 0.8 0.6 0.3 0.4 0.1 0.9 1.1 0.7 0.4 0.5 0.3 1.8 2.7 1.1

 Salivary gland 0.5 0.3 0.6 0.7 0.9 0.6 0.5 0.6 0.4 0.8 0.8 0.8 0.4 0.5 0.4 0.8 1.0 0.7

 Floor of mouth 0.1 0.3 0.0 0.1 0.1 0.1 - - 0.0 0.0 - - 0.1 0.1 0.1 0.5 0.8 0.3

 Gum and other mouth 0.5 0.6 0.3 0.6 0.8 0.5 0.5 0.7 0.3 1.2 1.2 1.2 0.2 0.3 0.2 1.1 1.4 0.9

 Nasopharynx 0.4 0.4 0.3 0.7 1.0 0.4 0.7 1.0 0.5 0.9 1.4 0.5 0.9 1.2 0.5 0.5 0.8 0.3

 Tonsil 0.1 0.2 - 0.1 0.1 0.1 0.1 0.2 0.0 0.1 0.1 0.2 0.1 0.0 0.1 1.0 1.7 0.4

 Oropharynx - - 0.0 0.1 0.2 0.1 0.1 - - 0.0 - 0.1 0.0 0.1 - 0.2 0.4 0.1

 Hypopharynx 0.1 - - 0.1 0.2 0.1 0.1 0.2 - 1.2 1.4 1.0 0.1 0.1 0.1 0.6 0.9 0.2

 Other oral cavity 

 and pharynx 0.1 - - 0.1 0.1 0.0 0.1 - - 0.2 0.2 0.1 - - - 0.2 0.3 0.1

 Digestive system 30.1 35.1 25.8 59.2 69.4 51.3 28.9 34.9 23.6 29.4 40.1 18.9 23.3 25.7 20.9 56.1 69.1 45.4

 Esophagus 0.6 1.0 0.2 1.5 2.1 1.0 0.6 0.9 0.3 1.4 1.7 1.0 1.1 1.5 0.7 3.0 5.1 1.2

 Stomach 4.9 5.9 4.1 8.5 11.7 6.0 4.6 6.0 3.4 2.9 3.6 2.2 4.8 6.0 3.5 5.3 7.4 3.6

 Small intestine 0.3 0.5 - 0.7 1.0 0.5 0.7 0.8 0.6 0.4 0.5 0.3 0.6 0.8 0.4 1.2 1.3 1.0

 Colon and rectum 17.3 19.0 16.0 36.9 41.7 33.3 15.2 17.3 13.6 6.0 6.9 5.1 11.3 11.5 11.2 32.0 37.7 27.4

 Colon excluding rectum 11.9 12.7 11.2 26.7 29.6 24.7 9.9 10.5 9.4 3.9 4.6 3.3 7.4 7.6 7.2 22.5 25.5 20.0

 Cecum 1.8 1.8 1.9 2.6 2.7 2.4 0.7 0.8 0.6 0.3 0.4 0.3 0.3 0.3 0.3 5.0 5.2 4.8

 Appendix 0.2 0.3 - 0.2 0.1 0.2 0.1 - - - 0.0 - 0.0 0.1 0.0 0.4 0.4 0.4

 Ascending colon 0.6 0.6 0.6 4.0 4.4 3.8 1.7 1.8 1.5 0.2 0.3 0.2 0.3 0.4 0.2 3.5 3.8 3.3

 Hepatic flexure 0.2 0.2 0.3 0.8 0.8 0.7 0.3 0.3 0.4 0.2 0.3 0.1 0.1 0.1 0.1 1.2 1.4 1.1

 Transverse colon 0.5 0.5 0.4 1.4 1.6 1.3 0.4 0.3 0.5 0.3 0.3 0.2 0.3 0.3 0.3 2.0 2.2 1.8

 Splenic flexure 0.2 0.3 0.2 0.8 0.8 0.7 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.9 1.1 0.7

 Descending colon 0.5 0.7 0.4 2.2 2.5 2.0 0.7 1.0 0.5 0.3 0.3 0.2 0.2 0.2 0.2 1.4 1.7 1.2

 Sigmoid colon 3.9 4.1 3.8 8.1 9.2 7.3 3.0 3.2 2.9 0.6 0.7 0.5 1.8 1.6 2.0 7.1 8.7 5.9

 Colon, NOS§ 3.9 4.3 3.6 6.7 7.4 6.2 2.7 2.8 2.6 1.9 2.1 1.6 4.1 4.5 3.8 1.0 1.2 0.9

 Rectum and junction 5.4 6.3 4.8 10.1 12.1 8.6 5.4 6.8 4.2 2.0 2.3 1.8 3.9 3.9 4.0 9.6 12.3 7.3

 Rectosigmoid junction 1.2 1.6 0.8 2.4 3.0 2.0 1.1 1.4 0.8 0.6 0.7 0.4 1.1 1.1 1.0 2.8 3.5 2.2

 Rectum 4.3 4.7 4.0 7.7 9.1 6.6 4.3 5.4 3.4 1.5 1.6 1.4 2.9 2.8 3.0 6.8 8.8 5.1

 Anus, anal canal, 

 and anorectum 0.2 0.2 0.2 0.6 0.6 0.5 0.2 0.2 0.1 0.4 0.4 0.5 0.4 0.5 0.2 1.0 0.9 1.0

 Liver and intrahepatic 

 bile duct 1.7 2.8 0.8 2.2 3.0 1.6 1.6 2.7 0.6 12.8 20.6 5.2 1.6 1.9 1.3 4.2 6.4 2.4

 Liver 1.5 2.4 0.8 2.0 2.7 1.4 1.5 2.6 0.6 12.5 20.1 5.2 1.4 1.7 1.0 3.8 5.8 2.0

 Intrahepatic bile duct 0.2 0.4 - 0.2 0.2 0.2 - - - 0.3 0.5 - 0.2 0.1 0.3 0.5 0.6 0.4

 Gallbladder 1.8 1.5 2.2 0.8 0.4 1.2 1.2 0.6 1.8 0.2 0.2 0.2 1.4 0.8 1.9 0.7 0.4 1.0

 Other biliary 0.2 0.3 0.2 0.8 0.9 0.7 0.9 1.2 0.7 0.8 1.0 0.6 0.3 0.4 0.3 0.9 1.2 0.8

 Pancreas 2.7 3.8 1.7 6.1 7.1 5.3 3.3 4.8 1.9 3.2 3.7 2.5 1.5 1.8 1.0 6.6 7.7 5.7

 Retroperitoneum 0.1 - - 0.4 0.4 0.3 0.1 0.1 0.1 0.4 0.4 0.4 0.2 0.3 0.1 0.3 0.4 0.3

 Peritoneum, omentum, 

 and mesentery 0.1 0.0 0.3 0.5 0.3 0.7 0.2 - 0.2 0.0 0.0 0.1 0.2 0.2 0.2 0.5 0.2 0.8

 Other digestive organs - - 0.0 0.3 0.4 0.2 0.3 0.3 0.2 0.9 1.1 0.7 0.0 0.1 0.0 0.3 0.3 0.2

Table 1.7. Overview and Summary Data: Age-Standardized Incidence Rates,* by Site and Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001†
22 MECC Monograph 

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER‡

 1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

 Respiratory system 15.8 27.6 5.4 22.8 34.9 13.0 24.4 45.4 5.9 10.8 17.0 4.9 13.1 21.9 4.0 43.1 55.0 33.6

 Nose, nasal cavity, 

 and middle ear 0.2 0.3 0.2 0.3 0.4 0.3 0.3 0.3 0.2 0.4 0.3 0.5 0.3 0.3 0.2 0.5 0.6 0.4

 Larynx 1.6 3.0 0.2 2.4 4.6 0.6 3.1 6.0 0.5 2.2 4.2 0.3 2.7 4.8 0.4 2.7 4.6 1.0

 Lung and bronchus 13.4 23.4 4.7 19.0 28.4 11.4 20.4 38.0 4.8 7.7 11.9 3.7 9.9 16.4 3.1 39.2 48.6 31.9

 Pleura 0.2 0.4 - 0.5 0.7 0.3 0.3 0.5 0.2 0.3 0.4 0.3 0.2 0.2 0.2 0.5 1.0 0.2

Trachea, mediastinum, and other 

respiratory organs 0.4 0.4 0.3 0.6 0.8 0.4 0.4 0.6 0.2 0.1 0.2 0.1 0.1 0.2 0.1 0.2 0.3 0.1

 Bones and joints 1.4 2.0 0.8 1.3 1.6 1.0 0.8 0.9 0.7 1.5 1.7 1.4 1.1 1.2 0.9 0.8 0.9 0.7

 Soft tissue including heart 1.3 1.4 1.2 2.7 3.2 2.2 2.0 2.3 1.7 2.8 3.0 2.7 1.1 1.3 1.0 2.3 2.8 1.9

 Skin excluding 

 basal and squamous 2.9 2.8 3.0 13.4 15.4 11.8 2.1 2.8 1.6 0.7 0.9 0.4 1.1 1.3 0.9 14.5 17.8 11.9

 Melanoma of the skin 2.6 2.4 2.7 10.8 11.6 10.2 1.0 1.3 0.8 0.3 0.3 0.3 0.5 0.6 0.5 12.7 15.2 10.9

 Other non-epithelial skin 0.4 0.5 0.3 2.6 3.9 1.7 1.1 1.6 0.8 0.4 0.7 0.2 0.5 0.8 0.3 1.8 2.6 1.0

 Breast 30.2 0.6 57.7 50.3 1.1 93.1 19.2 0.6 36.7 25.1 0.8 49.6 18.7 0.6 38.0 51.9 0.8 97.2

 Female genital system 12.9 0.0 24.6 16.4 0.0 30.5 8.1 0.0 15.5 6.4 0.0 12.7 6.6 0.0 13.7 19.6 0.0 37.1

 Cervix uteri 1.9 0.0 3.7 2.8 0.0 5.3 1.3 0.0 2.5 1.3 0.0 2.7 1.3 0.0 2.6 3.6 0.0 7.0

 Corpus and uterus, NOS§ 6.2 0.0 11.8 7.4 0.0 13.8 4.5 0.0 8.7 1.8 0.0 3.5 2.8 0.0 5.8 9.4 0.0 17.6

 Corpus uteri 6.0 0.0 11.5 6.3 0.0 11.6 4.0 0.0 7.5 0.8 0.0 1.6 1.5 0.0 3.1 9.2 0.0 17.3

 Uterus, NOS§ 0.2 0.0 0.4 1.2 0.0 2.2 0.6 0.0 1.1 1.0 0.0 1.9 1.3 0.0 2.6 0.2 0.0 0.3

 Ovary 4.0 0.0 7.7 5.0 0.0 9.4 1.9 0.0 3.6 2.7 0.0 5.4 2.2 0.0 4.6 5.3 0.0 10.0

 Vagina 0.2 0.0 0.3 0.2 0.0 0.4 0.1 0.0 0.2 0.1 0.0 0.2 0.1 0.0 0.2 0.3 0.0 0.5

 Vulva 0.6 0.0 1.1 0.6 0.0 1.0 0.2 0.0 0.3 0.4 0.0 0.8 0.2 0.0 0.4 0.8 0.0 1.4

 Other female 

 genital organs 0.0 0.0 0.0 0.3 0.0 0.6 0.1 0.0 0.2 0.1 0.0 0.2 0.1 0.0 0.3 0.3 0.0 0.5

 Male genital system 18.7 40.9 0.0 22.7 51.0 0.0 9.2 20.1 0.0 3.8 8.0 0.0 6.4 12.7 0.0 55.7 122.6 0.0

 Prostate 16.4 36.1 0.0 20.7 47.1 0.0 8.4 18.4 0.0 3.6 7.5 0.0 5.6 11.2 0.0 52.9 116.9 0.0

 Testis 1.9 3.9 0.0 1.9 3.8 0.0 0.7 1.4 0.0 0.2 0.5 0.0 0.7 1.4 0.0 2.5 4.9 0.0

 Penis 0.3 0.7 0.0 0.0 0.1 0.0 0.1 0.3 0.0 - - 0.0 - - 0.0 0.2 0.5 0.0

 Other male genital organs - - 0.0 0.0 0.1 0.0 0.0 0.0 0.0 - - 0.0 0.0 0.1 0.0 0.1 0.2 0.0

 Urinary system 14.9 25.2 6.2 24.1 40.1 11.2 11.9 20.7 4.3 19.2 30.8 8.0 10.4 16.7 3.8 20.9 32.7 11.5

 Urinary bladder 11.2 20.5 3.3 15.1 27.5 5.1 8.6 16.0 2.1 16.6 27.5 6.3 7.6 13.2 1.8 12.2 20.9 5.5

 Kidney and renal pelvis 3.6 4.6 2.8 8.5 11.8 5.8 3.1 4.3 2.2 2.4 3.0 1.7 2.7 3.4 1.9 8.2 11.1 5.7

 Ureter - - - 0.3 0.4 0.2 0.1 0.2 0.0 0.1 0.2 - 0.1 0.1 - 0.3 0.4 0.2

 Other urinary organs - - - 0.3 0.4 0.2 0.1 - - 0.1 0.2 0.0 0.0 0.1 0.0 0.2 0.3 0.1

 Eye and orbit 0.3 0.3 0.2 0.4 0.5 0.4 0.3 0.4 0.3 0.3 0.4 0.2 0.4 0.3 0.4 0.6 0.7 0.5

 Brain and other 

 nervous system 4.9 5.2 4.6 5.2 6.1 4.3 3.9 4.8 3.0 3.7 3.8 3.5 4.0 4.4 3.6 5.2 6.2 4.4

 Brain 4.1 4.3 4.0 4.9 5.8 4.0 3.6 4.6 2.8 3.2 3.3 3.0 3.7 4.1 3.3 4.9 5.8 4.0

 Cranial nerves and other 

 nervous system 0.8 0.9 0.6 0.3 0.3 0.3 0.2 0.2 0.2 0.5 0.5 0.5 0.3 0.3 0.3 0.4 0.3 0.4

Table 1.7. continued
 MECC Monograph 23

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER‡

 1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

 Endocrine system 6.1 2.9 9.1 8.2 4.2 11.8 4.6 2.4 6.8 2.5 2.0 2.9 3.4 2.1 4.8 6.8 3.8 9.7

 Thyroid 5.6 2.6 8.6 7.5 3.5 11.2 4.1 1.8 6.5 2.0 1.2 2.7 3.0 1.7 4.5 6.2 3.2 9.2

 Other endocrine 

 including thymus 0.4 0.4 0.5 0.7 0.8 0.7 0.5 0.6 0.3 0.5 0.9 0.2 0.4 0.4 0.4 0.6 0.7 0.5

 Lymphoma 10.6 12.1 9.3 18.6 20.6 16.9 12.9 14.4 11.4 16.3 20.0 12.6 8.9 10.3 7.4 15.3 18.3 12.6

 Hodgkin lymphoma 3.0 2.7 3.3 3.4 3.5 3.3 2.7 3.0 2.3 2.1 2.9 1.4 2.5 3.0 2.0 2.4 2.7 2.2

 Hodgkin - Nodal 2.9 2.6 3.1 3.4 3.5 3.3 2.6 3.0 2.2 2.1 2.8 1.3 2.4 2.8 1.9 2.3 2.6 2.1

 Hodgkin - Extranodal 0.1 - 0.2 0.1 0.1 0.0 0.1 - 0.1 0.1 0.1 0.1 0.2 0.2 0.1 0.0 0.1 0.0

 Non-Hodgkin lymphoma 7.6 9.4 6.0 15.2 17.1 13.6 10.2 11.4 9.1 14.2 17.1 11.3 6.4 7.3 5.4 12.9 15.7 10.5

 NHL - Nodal 5.3 6.8 4.0 11.8 12.8 10.9 7.9 8.8 6.9 11.0 13.4 8.5 4.8 5.5 4.1 8.6 10.5 6.9

 NHL - Extranodal 2.3 2.6 1.9 3.4 4.2 2.7 2.4 2.6 2.2 3.2 3.7 2.7 1.6 1.8 1.3 4.3 5.2 3.6

Myeloma 1.6 2.0 1.3 3.3 4.0 2.8 2.7 2.7 2.6 1.0 1.4 0.6 2.0 2.0 1.9 3.5 4.3 2.9

 Leukemia 6.9 8.5 5.5 8.6 10.5 6.9 6.4 7.8 5.1 6.0 6.7 5.3 6.3 7.1 5.5 8.8 11.0 6.9

 Lymphocytic leukemia 4.1 5.1 3.2 4.6 5.9 3.4 2.6 3.3 1.9 2.6 3.2 2.0 2.9 3.4 2.2 4.3 5.5 3.2

 Acute lymphocytic 

 leukemia 2.0 2.1 1.9 1.2 1.4 1.0 1.0 1.3 0.7 1.1 1.3 1.0 1.6 1.9 1.3 1.8 2.0 1.6

 Chronic lymphocytic 

 leukemia 1.8 2.4 1.2 3.0 3.8 2.3 1.3 1.5 1.2 1.3 1.7 0.9 1.1 1.3 0.8 2.2 3.1 1.4

 Other lymphocytic 

 leukemia 0.3 0.6 - 0.4 0.7 0.2 0.3 0.5 - 0.1 0.2 0.1 0.2 0.2 0.1 0.3 0.5 0.2

Myeloid and monocytic leukemia 2.7 3.1 2.3 3.4 3.8 3.0 3.1 3.8 2.5 2.3 2.2 2.4 2.7 2.8 2.7 4.1 5.0 3.3

 Acute myeloid 

 leukemia 1.8 2.1 1.5 2.3 2.5 2.1 2.1 2.7 1.5 1.1 1.1 1.0 1.4 1.5 1.3 2.7 3.2 2.2

 Acute monocytic 

 leukemia - - 0.0 0.1 0.1 0.1 0.1 0.2 - - 0.0 - 0.1 0.1 0.2 0.2 0.2 0.2

 Chronic myeloid 

 leukemia 0.7 0.6 0.7 0.9 1.0 0.8 0.9 0.9 0.9 1.2 1.0 1.3 1.1 1.1 1.1 1.1 1.4 0.8

 Other myeloid/ 

 monocytic leukemia 0.1 0.2 - 0.1 0.1 0.1 - - 0.0 - - - 0.1 0.1 0.1 0.1 0.1 0.1

 Other leukemia 0.1 0.3 0.0 0.6 0.8 0.5 0.7 0.7 0.7 1.1 1.3 0.9 0.7 0.9 0.5 0.4 0.5 0.4

 Other acute leukemia 0.1 0.2 0.0 0.4 0.5 0.3 0.4 0.3 0.4 0.1 0.2 0.1 0.5 0.6 0.3 0.2 0.2 0.2

Aleukemic, subleukemic, and 

NOS§ - - 0.0 0.2 0.3 0.2 0.3 0.3 0.3 1.0 1.1 0.8 0.2 0.3 0.2 0.2 0.3 0.2

 Miscellaneous 3.1 3.5 2.7 11.7 13.1 10.5 8.9 10.6 7.3 8.0 9.5 6.6 3.8 3.9 3.7 6.1 7.0 5.4

*Rates are per 100,000 and are age-standardized to the World Standard Million.

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

§NOS indicates “not otherwise specified.”

Table 1.7. continued
24 MECC Monograph 

Overview and Summary Data Chapter 1

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER‡

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

All Sites 2.2 3.2 3.0 0.9 1.3 1.2 2.0 3.3 2.6 1.5 2.2 1.9 0.9 1.3 1.2 0.5 0.8 0.6

 Oral cavity and pharynx 0.3 0.4 0.3 0.1 0.2 0.2 0.3 0.5 0.3 0.3 0.4 0.4 0.1 0.2 0.2 0.1 0.1 0.1

 Lip 0.1 0.1 - 0.1 0.1 0.1 0.2 0.3 0.2 0.0 0.1 - 0.1 0.1 0.1 0.0 0.0 0.0

 Tongue 0.1 0.2 0.1 0.0 0.1 0.1 0.1 0.2 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.0 0.1 0.0

 Salivary gland 0.1 0.1 0.2 0.0 0.1 0.1 0.1 0.2 0.2 0.1 0.2 0.2 0.1 0.1 0.1 0.0 0.0 0.0

 Floor of mouth 0.1 0.1 0.0 0.0 0.0 0.0 - - 0.0 0.0 - - 0.0 0.0 0.0 0.0 0.0 0.0

 Gum and other mouth 0.1 0.2 0.1 0.0 0.1 0.1 0.1 0.2 0.1 0.1 0.2 0.2 0.0 0.1 0.0 0.0 0.0 0.0

 Nasopharynx 0.1 0.2 0.1 0.0 0.1 0.0 0.1 0.2 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.0 0.0 0.0

 Tonsil 0.1 0.1 - 0.0 0.0 0.0 0.1 0.1 0.0 0.0 0.1 0.1 0.0 0.0 0.0 0.0 0.1 0.0

 Oropharynx - - 0.0 0.0 0.0 0.0 0.0 - - 0.0 - 0.0 0.0 0.0 - 0.0 0.0 0.0

 Hypopharynx 0.1 - - 0.0 0.0 0.0 0.1 0.1 - 0.1 0.2 0.2 0.0 0.0 0.0 0.0 0.0 0.0

 Other oral cavity 

 and pharynx 0.0 - - 0.0 0.0 0.0 0.0 - - 0.0 0.1 0.1 - - - 0.0 0.0 0.0

 Digestive system 0.9 1.4 1.2 0.4 0.6 0.5 0.9 1.5 1.1 0.7 1.1 0.7 0.4 0.6 0.6 0.2 0.3 0.2

 Esophagus 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.2 0.2 0.1 0.1 0.1 0.0 0.1 0.0

 Stomach 0.4 0.6 0.5 0.2 0.3 0.2 0.4 0.6 0.4 0.2 0.3 0.2 0.2 0.3 0.2 0.1 0.1 0.1

 Small intestine 0.1 0.2 - 0.0 0.1 0.1 0.1 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0

 Colon and rectum 0.7 1.0 0.9 0.3 0.5 0.4 0.7 1.1 0.9 0.3 0.4 0.4 0.3 0.4 0.4 0.1 0.2 0.2

 Colon excluding rectum 0.6 0.9 0.8 0.3 0.4 0.4 0.5 0.8 0.7 0.2 0.4 0.3 0.2 0.3 0.3 0.1 0.2 0.2

 Cecum 0.2 0.3 0.3 0.1 0.1 0.1 0.1 0.2 0.2 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.1 0.1

 Appendix 0.1 0.1 - 0.0 0.0 0.0 0.1 - - - 0.0 - 0.0 0.0 0.0 0.0 0.0 0.0

 Ascending colon 0.1 0.2 0.2 0.1 0.2 0.1 0.2 0.3 0.3 0.1 0.1 0.1 0.0 0.1 0.1 0.0 0.1 0.1

 Hepatic flexure 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0

 Transverse colon 0.1 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.0 0.1 0.1 0.0 0.1 0.0

 Splenic flexure 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0

 Descending colon 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.3 0.2 0.1 0.1 0.1 0.0 0.1 0.1 0.0 0.1 0.0

 Sigmoid colon 0.3 0.5 0.4 0.2 0.2 0.2 0.3 0.5 0.4 0.1 0.1 0.1 0.1 0.2 0.2 0.1 0.1 0.1

 Colon, NOS§ 0.3 0.5 0.4 0.1 0.2 0.2 0.3 0.4 0.4 0.2 0.3 0.2 0.2 0.3 0.2 0.0 0.0 0.0

 Rectum and 

 rectosigmoid junction 0.4 0.6 0.5 0.2 0.3 0.2 0.4 0.7 0.5 0.2 0.3 0.2 0.2 0.2 0.2 0.1 0.1 0.1

 Rectosigmoid junction 0.2 0.3 0.2 0.1 0.1 0.1 0.2 0.3 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.1

 Rectum 0.3 0.5 0.5 0.1 0.2 0.2 0.4 0.6 0.4 0.1 0.2 0.2 0.1 0.2 0.2 0.1 0.1 0.1

 Anus, anal canal, 

 and anorectum 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0

 Liver and intrahepatic 

 bile duct 0.2 0.4 0.2 0.1 0.1 0.1 0.2 0.4 0.2 0.4 0.8 0.4 0.1 0.2 0.1 0.1 0.1 0.1

 Liver 0.2 0.4 0.2 0.1 0.1 0.1 0.2 0.4 0.2 0.4 0.8 0.4 0.1 0.2 0.1 0.1 0.1 0.1

 Intrahepatic bile duct 0.1 0.1 - 0.0 0.0 0.0 - - - 0.1 0.1 - 0.0 0.0 0.1 0.0 0.0 0.0

 Gallbladder 0.2 0.3 0.3 0.0 0.0 0.1 0.2 0.2 0.3 0.1 0.1 0.1 0.1 0.1 0.2 0.0 0.0 0.0

 Other biliary 0.1 0.1 0.1 0.0 0.1 0.1 0.2 0.3 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.0 0.0 0.0

 Pancreas 0.3 0.5 0.3 0.1 0.2 0.2 0.3 0.6 0.3 0.2 0.4 0.3 0.1 0.2 0.1 0.1 0.1 0.1

 Retroperitoneum 0.0 - - 0.0 0.1 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.0 0.0 0.0 0.0

Table 1.8. Overview and Summary Data: Standard Errors of the Age-Standardized Incidence Rates* Shown in Table 1.7, by Site and Sex, in Cyprus, Israel (Jews and Arabs), Egypt, 

Jordan, and US SEER − 1996-2001†
 MECC Monograph 25

Overview and Summary Data Chapter 1

Table 1.8. continued

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER‡

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

 Peritoneum, omentum, 

 and mesentery 0.1 0.0 0.1 0.0 0.0 0.1 0.1 - 0.1 0.0 0.0 0.1 0.0 0.0 0.1 0.0 0.0 0.0

 Other digestive organs - - 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.2 0.1 0.0 0.0 0.0 0.0 0.0 0.0

 Respiratory system 0.7 1.3 0.5 0.3 0.5 0.3 0.9 1.7 0.6 0.4 0.8 0.4 0.3 0.6 0.2 0.2 0.3 0.2

 Nose, nasal cavity, 

 and middle ear 0.1 0.1 0.1 0.0 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.0 0.0 0.0

 Larynx 0.2 0.4 0.1 0.1 0.2 0.1 0.3 0.6 0.2 0.2 0.4 0.1 0.1 0.3 0.1 0.0 0.1 0.0

 Lung and bronchus 0.6 1.2 0.5 0.2 0.4 0.2 0.8 1.6 0.5 0.4 0.6 0.3 0.3 0.5 0.2 0.2 0.3 0.2

 Pleura 0.1 0.1 - 0.0 0.1 0.0 0.1 0.2 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.0 0.0 0.0

Trachea, mediastinum, and other 

respiratory organs 0.1 0.2 0.1 0.0 0.1 0.0 0.1 0.2 0.1 0.0 0.1 0.0 0.0 0.1 0.0 0.0 0.0 0.0

 Bones and joints 0.2 0.4 0.2 0.1 0.1 0.1 0.1 0.2 0.2 0.1 0.2 0.2 0.1 0.1 0.1 0.0 0.0 0.0

 Soft tissue including heart 0.2 0.3 0.3 0.1 0.1 0.1 0.2 0.3 0.3 0.2 0.3 0.3 0.1 0.1 0.1 0.0 0.1 0.1

 Skin excluding 

 basal and squamous 0.3 0.4 0.4 0.2 0.3 0.3 0.2 0.4 0.3 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.2 0.1

 Melanoma of the skin 0.3 0.4 0.4 0.2 0.3 0.2 0.2 0.3 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1

 Other non-epithelial skin 0.1 0.2 0.1 0.1 0.2 0.1 0.2 0.3 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.0 0.1 0.0

 Breast 0.9 0.2 1.8 0.4 0.1 0.7 0.7 0.2 1.4 0.6 0.2 1.2 0.4 0.1 0.7 0.2 0.0 0.4

 Female genital system 0.6 0.0 1.2 0.2 0.0 0.4 0.5 0.0 0.9 0.3 0.0 0.6 0.2 0.0 0.4 0.1 0.0 0.2

 Cervix uteri 0.2 0.0 0.5 0.1 0.0 0.2 0.2 0.0 0.4 0.1 0.0 0.3 0.1 0.0 0.2 0.1 0.0 0.1

 Corpus and uterus, NOS§ 0.4 0.0 0.8 0.2 0.0 0.3 0.4 0.0 0.7 0.2 0.0 0.3 0.1 0.0 0.3 0.1 0.0 0.2

 Corpus uteri 0.4 0.0 0.8 0.1 0.0 0.3 0.3 0.0 0.7 0.1 0.0 0.2 0.1 0.0 0.2 0.1 0.0 0.2

 Uterus, NOS§ 0.1 0.0 0.1 0.1 0.0 0.1 0.1 0.0 0.2 0.1 0.0 0.2 0.1 0.0 0.2 0.0 0.0 0.0

 Ovary 0.3 0.0 0.7 0.1 0.0 0.2 0.2 0.0 0.4 0.2 0.0 0.4 0.1 0.0 0.3 0.1 0.0 0.1

 Vagina 0.1 0.0 0.1 0.0 0.0 0.0 0.1 0.0 0.1 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0

 Vulva 0.1 0.0 0.2 0.0 0.0 0.1 0.1 0.0 0.1 0.1 0.0 0.2 0.0 0.0 0.1 0.0 0.0 0.0

 Other female 

 genital organs 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.0 0.1 0.0 0.0 0.1 0.0 0.0 0.1 0.0 0.0 0.0

 Male genital system 0.7 1.5 0.0 0.3 0.6 0.0 0.5 1.2 0.0 0.3 0.6 0.0 0.2 0.4 0.0 0.2 0.4 0.0

 Prostate 0.6 1.4 0.0 0.2 0.5 0.0 0.5 1.1 0.0 0.3 0.5 0.0 0.2 0.4 0.0 0.2 0.4 0.0

 Testis 0.3 0.5 0.0 0.1 0.2 0.0 0.1 0.2 0.0 0.1 0.1 0.0 0.1 0.1 0.0 0.0 0.1 0.0

 Penis 0.1 0.2 0.0 0.0 0.0 0.0 0.1 0.1 0.0 - - 0.0 - - 0.0 0.0 0.0 0.0

 Other male genital organs - - 0.0 0.0 0.0 0.0 0.0 0.0 0.0 - - 0.0 0.0 0.0 0.0 0.0 0.0 0.0

 Urinary system 0.6 1.2 0.6 0.3 0.5 0.2 0.6 1.1 0.5 0.6 1.0 0.5 0.3 0.5 0.2 0.1 0.2 0.1

 Urinary bladder 0.5 1.1 0.4 0.2 0.4 0.2 0.5 1.0 0.3 0.5 1.0 0.4 0.2 0.4 0.2 0.1 0.2 0.1

 Kidney and renal pelvis 0.3 0.5 0.4 0.2 0.3 0.2 0.3 0.5 0.3 0.2 0.3 0.2 0.1 0.2 0.2 0.1 0.1 0.1

 Ureter - - - 0.0 0.1 0.0 0.1 0.1 0.0 0.0 0.1 - 0.0 0.0 - 0.0 0.0 0.0

 Other urinary organs - - - 0.0 0.1 0.0 0.1 - - 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0

 Eye and orbit 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.0 0.0 0.0
26 MECC Monograph 

Overview and Summary Data Chapter 1

Table 1.8. continued

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER‡

1999-2001

Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

 Brain and other 

 nervous system 0.4 0.6 0.6 0.1 0.2 0.2 0.3 0.5 0.4 0.2 0.3 0.3 0.2 0.2 0.2 0.1 0.1 0.1

 Brain 0.4 0.5 0.5 0.1 0.2 0.2 0.3 0.5 0.4 0.2 0.3 0.3 0.1 0.2 0.2 0.1 0.1 0.1

 Cranial nerves and other 

 nervous system 0.2 0.3 0.2 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.0 0.0 0.0

 Endocrine system 0.5 0.5 0.8 0.2 0.2 0.3 0.3 0.3 0.5 0.2 0.2 0.3 0.1 0.2 0.2 0.1 0.1 0.1

 Thyroid 0.4 0.4 0.7 0.2 0.2 0.3 0.3 0.3 0.5 0.2 0.2 0.3 0.1 0.1 0.2 0.1 0.1 0.1

 Other endocrine 

 including thymus 0.1 0.2 0.2 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.0 0.1 0.1 0.0 0.0 0.0

 Lymphoma 0.6 0.9 0.8 0.2 0.4 0.3 0.6 0.9 0.7 0.5 0.7 0.6 0.2 0.4 0.3 0.1 0.2 0.1

 Hodgkin lymphoma 0.3 0.5 0.5 0.1 0.2 0.2 0.2 0.3 0.3 0.2 0.3 0.2 0.1 0.2 0.1 0.0 0.1 0.1

 Hodgkin - Nodal 0.3 0.4 0.5 0.1 0.2 0.1 0.2 0.3 0.3 0.1 0.2 0.2 0.1 0.2 0.1 0.0 0.1 0.1

 Hodgkin - Extranodal 0.1 - 0.1 0.0 0.0 0.0 0.0 - 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0

 Non-Hodgkin lymphoma 0.5 0.8 0.6 0.2 0.3 0.3 0.5 0.8 0.7 0.4 0.7 0.6 0.2 0.3 0.3 0.1 0.2 0.1

 NHL - Nodal 0.4 0.7 0.5 0.2 0.3 0.2 0.5 0.7 0.6 0.4 0.6 0.5 0.2 0.3 0.2 0.1 0.1 0.1

 NHL - Extranodal 0.3 0.4 0.3 0.1 0.2 0.1 0.2 0.4 0.3 0.2 0.3 0.3 0.1 0.2 0.1 0.1 0.1 0.1

Myeloma 0.2 0.4 0.3 0.1 0.2 0.1 0.3 0.4 0.4 0.1 0.2 0.1 0.1 0.2 0.2 0.0 0.1 0.1

 Leukemia 0.5 0.8 0.6 0.2 0.3 0.2 0.4 0.6 0.5 0.3 0.4 0.4 0.2 0.3 0.3 0.1 0.1 0.1

 Lymphocytic leukemia 0.4 0.6 0.5 0.1 0.2 0.1 0.2 0.4 0.3 0.2 0.3 0.2 0.1 0.2 0.2 0.1 0.1 0.1

 Acute lymphocytic 

 leukemia 0.3 0.4 0.4 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.0 0.1 0.1

 Chronic lymphocytic 

 leukemia 0.2 0.4 0.2 0.1 0.2 0.1 0.2 0.3 0.3 0.1 0.2 0.2 0.1 0.1 0.1 0.0 0.1 0.0

 Other lymphocytic 

 leukemia 0.1 0.2 - 0.0 0.1 0.0 0.1 0.2 - 0.0 0.1 0.1 0.0 0.1 0.0 0.0 0.0 0.0

 Myeloid and monocytic 

 leukemia 0.3 0.5 0.4 0.1 0.2 0.1 0.3 0.4 0.3 0.2 0.2 0.2 0.1 0.2 0.2 0.1 0.1 0.1

 Acute myeloid 

 leukemia 0.2 0.4 0.3 0.1 0.1 0.1 0.2 0.4 0.3 0.1 0.2 0.2 0.1 0.1 0.1 0.0 0.1 0.1

 Acute monocytic 

 leukemia - - 0.0 0.0 0.0 0.0 0.1 0.1 - - 0.0 - 0.0 0.0 0.0 0.0 0.0 0.0

 Chronic myeloid 

 leukemia 0.1 0.2 0.2 0.1 0.1 0.1 0.1 0.2 0.2 0.1 0.2 0.2 0.1 0.1 0.1 0.0 0.0 0.0

 Other myeloid/ 

 monocytic leukemia 0.1 0.1 - 0.0 0.0 0.0 - - 0.0 - - - 0.0 0.0 0.0 0.0 0.0 0.0

 Other leukemia 0.1 0.1 0.0 0.0 0.1 0.1 0.1 0.2 0.2 0.1 0.2 0.2 0.1 0.1 0.1 0.0 0.0 0.0

 Other acute leukemia 0.1 0.1 0.0 0.0 0.1 0.0 0.1 0.1 0.1 0.0 0.1 0.0 0.1 0.1 0.1 0.0 0.0 0.0

Aleukemic, subleukemic, and NOS§ - - 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.1 0.2 0.2 0.0 0.1 0.1 0.0 0.0 0.0

 Miscellaneous 0.3 0.5 0.4 0.2 0.3 0.2 0.5 0.8 0.6 0.4 0.6 0.5 0.2 0.2 0.2 0.1 0.1 0.1

*Rates are per 100,000 and are age-standardized to the World Standard Million.

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

§NOS indicates “not otherwise specified.”
 MECC Monograph 27

Overview and Summary Data Chapter 1

REFERENCES

[1] Middle East Cancer Consortium. Manual of standards for cancer registration. 2005. Available at: http://mecc.cancer.gov/MECC_Manual_of_Standards.PDF. [Last Accessed: 1/06].

[2] Surveillance, Epidemiology and End Results, NCI. SEER*Stat 6.1. 2005 

Available at: http://seer.cancer.gov/seerstat/. [Last Accessed: 1/06].

[3] Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in 

five continents, volume VIII. IARC Scientific Publication No. 155. Lyon 

(France): International Agency for Research on Cancer; 2002.

[4] Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence. Mortality and prevalence worldwide. IARC cancer base no. 5, 

version 2.0. Lyon (France): IARC Press; 2004.
28 MECC Monograph 
 MECC Monograph 29

Esophageal Cancer Chapter 2

GÜL ERGÖR

BACKGROUND

Cancer of the esophagus is the eighth most common cancer 

worldwide [1], with more than 400,000 cases per year. Incidence 

is highest in western and south central Asia. The geographical 

differences in incidence that are observed are more extreme than for 

any other cancer. A high-risk area known as the “esophageal cancer 

belt” ranges from northern Iran all the way to north central China 

[2]. 

The 2 main types of esophageal cancer are squamous cell 

carcinoma and adenocarcinoma. Squamous cell carcinoma is seen 

predominantly in developing countries and is associated with 

tobacco and alcohol consumption as well as with hot beverage 

consumption and malnutrition. Low intakes of fruits and vegetables 

are also risk factors for squamous cell cancers. Adenocarcinoma 

is mostly found in developed countries, and is mostly related to 

obesity and chronic gastroesophageal reflux. This reflux causes a 

clinical condition called Barrett’s esophagus, which is considered a 

premalignant lesion [3].

Many risk factors play a role in the etiology of esophageal cancer, 

although these vary with geographic region. For example, betel 

chewing and oral consumption of opium are factors primarily found 

in Southeast Asia and the Caspian Sea area [2]. The factor for which 

there is the most convincing evidence is alcohol consumption, 

and this risk is even greater among drinkers who also smoke. The 

alcohol relationship is not specific to a type of drink, but to the level 

of consumption. 

McCredie et al. reported that migrants from the Middle East to 

Australia had a lower cancer incidence than other Australians for 

many sites, including the esophagus [4]. A characteristic of this 

disease is that it shows marked differences between ethnic groups in 

the same country or same geographical areas. For example, Scotland 

has very high rates compared with England and Ireland [5]. In a 

recent study by de Martel et al., high prevalence of Helicobacter 

pylori was reported as a protective factor for esophageal 

adenocarcinoma (OR = 0.37; 95% CI, 0.16-0.88) [6].

RESULTS 

Overall Incidence 

Table 2.1 displays the age-standardized incidence rates in the MECC 

countries and US SEER. The incidence of esophageal cancer in the 

MECC countries during this period (1996-2001) was among the 

lowest in the world. The rates worldwide were 11.5 in males and 4.7 

in females [7]. In MECC countries, the highest rate was in Israeli 

Jews (1.5), and the lowest was in Israeli Arabs and Cypriots (0.6). 

Egyptians (1.4) showed a rate similar to that of Israeli Jews, while 

Jordanians had a slightly lower rate (1.1). In comparison, US SEER 

rates for the same years were more than twice as high (3.0). Because 

the MECC countries are outside the esophageal cancer belt, lower 

rates than in this high-risk region are expected. 

The low rates of esophageal cancer in the MECC countries 

might also be explained by the relatively low levels of alcohol 

consumption in Arab countries with a Muslim majority. Alcohol 

consumption by Israeli Jews is lower than in most Western countries, 

but higher than consumption by Israeli Arabs. According to Neumark 

et al., the prevalence of any non-ritual alcohol consumption by 

males over a 1-month period was 67% in Israeli Jews and 46% in 

Israeli Arabs. The differences were even more marked in females: 

33% in Israeli Jews and 7% in Israeli Arabs [8]. Data from the 
30 MECC Monograph 

Esophageal Cancer Chapter 2

Table 2.1. Esophageal Cancer: Number of Cases, Age Distribution, and Age-Standardized Incidence Rates, by Age and Sex, in Cyprus, Israel (Jews and 

Arabs), Egypt, Jordan, and US SEER − 1996-2001*

Cyprus 

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

 1996-2001

Egypt 

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 23 19 4 665 390 275 20 14 6 94 58 36 144 99 45 4,826 3,616 1,210

Age Groups (Distribution)

<50 y - - 0.0% 5.6% 6.9% 3.6% 15.0% - - 26.6% 27.6% 25.0% 18.1% 18.2% 17.8% 7.6% 8.2% 5.6%

50-69 y 43.5% 42.1% - 32.2% 36.9% 25.5% 35.0% 50.0% 0.0% 55.3% 56.9% 52.8% 48.6% 48.5% 48.9% 44.6% 48.1% 33.9%

70+ y 47.8% 47.4% - 62.3% 56.2% 70.9% 50.0% 35.7% 83.3% 18.1% 15.5% 22.2% 33.3% 33.3% 33.3% 47.9% 43.7% 60.5%

Age Groups (Rates)‡

Total rate 0.6 1.0 0.2 1.5 2.1 1.0 0.6 0.9 0.3 1.4 1.7 1.0 1.1 1.5 0.7 3.0 5.1 1.2

<50 y - - 0.0 0.1 0.2 0.1 0.1 - - 0.3 0.4 0.2 0.2 0.2 0.1 0.3 0.5 0.1

50-69 y 2.0 3.3 - 4.5 6.6 2.7 1.3 2.8 0.0 5.0 6.6 3.6 3.4 4.4 2.2 11.2 19.1 4.1

70+ y 4.6 8.8 - 16.6 21.2 13.3 7.7 8.9 6.8 8.2 8.9 7.6 9.8 14.4 5.7 24.5 42.0 12.2

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Rates are per 100,000 and are age-standardized to the World Standard Million.

same study showed that Ashkenazi Israeli Jews had higher drinking 

patterns than Sephardi Israeli Jews (68% and 59%, respectively) [9]. 

In contrast to alcohol, in almost all of the MECC countries there 

is a high prevalence of smoking, which would tend to increase 

esophageal cancer rates. Smoking prevalence in Israel was 39% 

in males during 1999-2001, according to the First Israeli National 

Health and Nutrition Survey [10]. Similarly, smoking is very 

common in the other MECC countries. The low esophageal cancer 

rates suggest under-diagnosis of esophageal cancers in all the 

countries in the region. 

As indicated above, world esophageal cancer rates were 2 to 3 

times higher in males (11.5) than in females (4.7). Sex ratios for 

Middle Eastern populations can be judged from data taken from 

GLOBOCAN, which are presented in Table 2.2. The ratios are 

similar to those seen in the MECC data. Most ratios in the MECC 

data were around 2, except in Israeli Arabs, where the male rate 

was 3 times the female rate, and in Cyprus, where the male rate 

was 5 times the female rate (Table 2.1). However, due to the very 

small numbers, these differences in ratios should be interpreted with 

caution. The sex ratio in the United States was more than 4 (Table 

2.1), which may be explained by the fact that the majority of these 

cancers were adenomatous, originating from Barrett’s esophagus, 

which is 7 times more commonly seen in males [2]. 

Age

Esophageal cancer incidence increases with age in all countries. In 

the MECC populations and in SEER, the age-specific rates were 

very low below 50 years of age (Table 2.1). Between ages 50-69 

years, the rates were 5.0 in Egyptians, 4.5 in Israeli Jews, 3.4 in 
 MECC Monograph 31

Esophageal Cancer Chapter 2

Subsites

The MECC registries record the localization of tumors within the 

esophagus; however, the majority of the esophageal cancers were 

recorded as occurring at an unspecified site in 4 of the populations: 

Cypriots (56.5%), Israeli Jews (60.8%), Israeli Arabs (60.0%), and 

Jordanians (72.2%) (Table 2.4). Only in Egypt were a majority 

recorded for a specified site. The most common specific site of 

localization in the MECC countries was in the “abdominal and onethird distal” part of the esophagus, which was recorded far more 

frequently than were cancers localized in the upper one-third and 

middle one-third of the esophagus.

Basis of Diagnosis

The proportion of microscopically confirmed esophageal cancer 

cases varied from 85.4% to 100% in the MECC countries (Table 

2.3). US SEER results had a very high (96.1%) microscopic 

confirmation, which could be explained by the country’s highly 

technology-dependent health care system. This high rate is less 

expected in MECC countries, where patients may generally receive 

less aggressive management of their disease. 

In Cyprus, all cases were microscopically confirmed. This may 

indicate that some cases were missing, because one would expect 

that there would be patients treated palliatively whose cancers 

were not microscopically confirmed. Evidently, if there were such 

patients, they were not notified to the registry. Likewise, the very 

high proportion of microscopically confirmed cases among Israeli 

Arabs and Jordanians suggests that some clinically diagnosed cases 

were missed. 

Table 2.2. Esophageal Cancer: Age-Standardized Incidence 

Rates,* by Sex, in Middle Eastern Countries − 1998-2002

Country Male Female

Cyprus 1.7 0.3

Iraq 1.2 0.9

Israel 2.3 1.1

Jordan 1.4 0.7

Kuwait 1.7 1.8

Lebanon 1.4 0.7

Syrian Arab Republic 1.4 0.9

Turkey 2.1 1.5

*Rates are per 100,000 and are age-standardized to the World Standard Million.

Source: Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence. Mortality and 

prevalence worldwide. IARC cancer base no. 5, version 2.0. Lyon (France): IARC Press; 2004.

Jordanians, 2.0 in Cypriots, and 1.3 in Israeli Arabs. The highest 

rates in the MECC populations were in the 70-and-older group, 

ranging from 4.6 in Cypriots to 16.6 in Israeli Jews. The age-specific 

rates also varied by sex. 

Histology

Squamous cell carcinoma was the most common type of esophageal 

cancer in each of the MECC populations (Table 2.3). However, it 

is important to note that the ratio of squamous cell carcinoma to 

adenocarcinoma (the other main type of esophageal cancer) was far 

higher in females than in males. Overall, approximately half of the 

esophageal cancers were of the squamous cell type in Cyprus and 

Israel. In Egypt and Jordan, the proportions reached above 60%, 

which is typical for developing countries. In the United States, the 

proportion of adenocarcinomas was higher than for squamous cell 

carcinomas, as in other Western countries (Table 2.3). 
32 MECC Monograph 

Esophageal Cancer Chapter 2

SUMMARY AND CONCLUSIONS

The low incidence rates reported for esophageal cancer are most 

probably due to low consumption of alcohol in the Middle East 

compared with other parts of the world. However, the possibility 

of under-diagnosis is also a partial explanation. In some countries, 

male/female ratios were very high; this might be a result of genderrelated problems of access to health care due to traditional or 

organizational factors, though it could also be due to fluctuations 

in small numbers. Discrepancies between Israeli Jews and Arabs 

might be partly due to ethnic distinctions, but differences in alcohol 

consumption and smoking are the most likely contributing causes.

Table 2.3. Esophageal Cancer: Number of Cases and Proportions of Histologic Type and Microscopic Confirmation, by Sex, in Cyprus, Israel (Jews and 

Arabs), Egypt, Jordan, and US SEER − 1996-2001*

Cyprus 

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs) 

1996-2001

Egypt 

1999-2001

Jordan 

1996-2001

US SEER†

 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases microscopically 

confirmed 23 19 4 568 338 230 19 14 5 83 54 29 141 96 45 4640 3499 1141

Microscopically confirmed 100.0% 100.0% 100.0% 85.4% 86.7% 83.6% 95.0% 100.0% 83.3% 88.3% 93.1% 80.5% 97.9% 97.0% 100.0% 96.1% 97.0% 94.3%

Distribution of Microscopically Confirmed Cases

Histologic distribution‡ 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Carcinoma 100.0% 100.0% 100.0% 98.1% 97.0% 99.6% 94.7% 92.9% 100.0% 100.0% 100.0% 100.0% 97.2% 97.9% 95.6% 98.9% 98.9% 98.8%

Squamous cell carcinoma 56.5% 52.6% 75.0% 50.5% 39.6% 66.5% 52.6% 50.0% 60.0% 67.5% 61.1% 79.3% 62.4% 56.3% 75.6% 41.5% 35.7% 59.4%

Adenocarcinoma 43.5% 47.4% - 39.1% 48.5% 25.2% 42.1% 42.9% - 20.5% 25.9% 10.3% 29.8% 37.5% 13.3% 50.5% 57.1% 30.4%

Other specified carcinoma 0.0% 0.0% 0.0% 3.0% 3.8% 1.7% 0.0% 0.0% 0.0% - - 0.0% 0.0% 0.0% 0.0% 1.9% 1.8% 2.5%

Unspecified carcinoma 0.0% 0.0% 0.0% 5.5% 5.0% 6.1% 0.0% 0.0% 0.0% 9.6% 9.3% 10.3% 5.0% 4.2% 6.7% 4.9% 4.3% 6.5%

Sarcoma 0.0% 0.0% 0.0% 0.5% 0.9% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.2% 0.2% -

Other histologies 0.0% 0.0% 0.0% 0.5% - - - - 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.4% 0.4% 0.4%

Unspecified cancer 0.0% 0.0% 0.0% 0.9% 1.5% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 2.8% - - 0.6% 0.5% 0.8%

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Percentages should sum over a column to 100% (with some rounding). However, where a percentage has been suppressed because it is based on only 1 or 2 cases, the remaining percentages will not sum to 100%.
 MECC Monograph 33

Esophageal Cancer Chapter 2

REFERENCES

[1] Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of 25 

major cancers in 1990. Int J Cancer 1999;80:827-41.

[2] Stewart BW, Kleihues P, editors. World cancer report. Lyon (France): 

International Agency for Research on Cancer; 2003.

[3] Forman D. Review article: oesophago-gastric adenocarcinoma – an epidemiological perspective. Aliment Pharmacol Ther 2004;20:55-60.

[4] McCredie M, Coates M, Grulich A. Cancer incidence in migrants to New 

South Wales (Australia) from the Middle East, 1972-91. Cancer Causes 

Control 1994;5:414-21.

[5] Corley DA, Buffler PA. Oesophageal and gastric cardia adenocarcinomas: 

analysis of regional variation using the Cancer Incidence in Five Continents database. Int J Epidemiol 2001;30:1415-25.

[6] de Martel C, Llosa AE, Farr SM, Friedman GD, Vogelman JH, Orentreich 

N, et al. Helicobacter pylori infection and the risk of development of 

Table 2.4. Esophageal Cancer: Number of Cases and Proportions of Subsites, by Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 

1996-2001

Cyprus 

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs) 

1996-2001

Egypt 

1999-2001

Jordan 

1996-2001

US SEER*

 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 23 19 4 665 390 275 20 14 6 94 58 36 144 99 45 4,826 3,616 1,210

Total percentage† 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Abdominal and distal 1/3 26.1% 31.6% 0.0% 25.9% 29.2% 21.1% 25.0% 28.6% - 48.9% 60.3% 30.6% 18.1% 16.2% 22.2% 53.6% 58.2% 40.0%

Other subsites 17.4% - - 13.4% 9.7% 18.5% 15.0% 21.4% 0.0% 20.2% 15.5% 27.8% 9.7% 8.1% 13.3% 36.3% 32.6% 47.5%

NOS‡ 56.5% 57.9% - 60.8% 61.0% 60.4% 60.0% 50.0% 83.3% 30.9% 24.1% 41.7% 72.2% 75.8% 64.4% 10.1% 9.3% 12.5%

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

†Percentages should sum over a column to 100% (with some rounding). However, where a percentage has been suppressed because it is based on only 1 or 2 cases, the remaining percentages will not sum to 100%.

‡NOS indicates “not otherwise specified.”

esophageal adenocarcinoma. J Infect Dis 2005;191:761-7.

[7] Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence. Mortality and prevalence worldwide. IARC cancer base no. 5, 

version 2.0. Lyon (France): IARC Press; 2004.

[8] Neumark YD, Rahav G, Teichman M, Hasin D. Alcohol drinking patterns among Jewish and Arab men and women in Israel. J Stud Alcohol 

2001;62:443-7.

[9] Aharonovich E, Hasin D, Rahav G, Meydan J, Neumark Y. Differences in 

drinking patterns among Ashkenazic and Sephardic Israeli adults. J Stud 

Alcohol 2001;62:301-5.

[10] Baron-Epel O, Haviv-Messika A, Tamir D, Nitzan-Kaluski D, Green M. 

Multiethnic differences in smoking in Israel: pooled analysis from three 

national surveys. Eur J Public Health 2004;14:384-9.
34 MECC Monograph 
 MECC Monograph 35

Stomach Cancer Chapter 3

GÜL ERGÖR

BACKGROUND

Stomach, or gastric, cancer incidence is second only to lung cancer 

worldwide, with an estimated 870,000 new cases and 650,000 deaths 

every year. The high-risk areas are East Asia, South America, and 

Eastern Europe. Data show that second-generation migrants from the 

high- to low-risk areas have lower incidence rates than their parents. 

Incidence rates are twice as high in males as in females. Thirty-eight 

percent of the world’s stomach cancer cases occur in China, and it is 

the most frequent cancer in males in other parts of East Asia. Agestandardized incidence rates (ASRs) are the highest in the world in 

Japan (77.9 per 100,000 in men; 33.3 in women) [1,2].

The major risk factors for stomach cancer are hypothesized to 

be nutritional, including inadequate intake of fresh fruits and 

vegetables, and high intake of salt, smoked fish, and meat. 

Refrigeration of food is considered protective. Vitamin C, contained 

in vegetables and fruits, may be protective for stomach cancer. 

Other possibly protective nutritional factors are whole-grain cereal, 

carotenoids, allium compounds (e.g., garlic), and green tea [3]. 

Smoking carries a slightly increased risk for stomach cancer [4], 

and alcohol does not affect risk other than in the gastric cardia [5]. 

Smoking is quite common in countries of the Middle East Cancer 

Consortium (MECC) [6-9]. 

Another important risk factor is Helicobacter pylori infection. 

Other gastric diseases, such as ulcer and atrophic gastritis, elevate 

gastric pH, thus causing anaerobic bacterial colonization in the 

stomach. H. pylori prevalence ranges from 25% in developed 

countries to 80%-90% in the developing countries [10]. It is now 

considered as the principal cause of chronic gastritis and peptic 

ulcer disease, and is a key risk factor for the development of gastric 

cancer [11,12]. The prevalence of H. pylori is thought to be high in 

MECC countries. In Israel, the prevalence has been reported to be 

72% in a rural population and 65% in an urban population, which 

is higher than in the United States and Western Europe, but lower 

than in developing countries [13]. Another study has reported 33% 

positive for H. pylori in an elderly population in Israel [14], and a 

case-control study in Israel found 63% positivity among the healthy 

controls [15]. In a population of Jordanian endoscopy patients, 82% 

prevalence was reported [16], but there is no information for the 

general population. 

RESULTS

Overall Incidence 

Stomach cancer incidence in the MECC countries during the period 

1996-2001 was low (Table 3.1), compared with the world ASR of 

10.3 in females and 22.0 in males [1]. The incidence was highest in 

Israeli Jews (8.5), followed by Cypriots (4.9), Jordanians (4.8), and 

Israeli Arabs (4.6) (Table 3.1). Although a study from Jordan reports 

that the characteristics of gastric cancers diagnosed there resemble 

those in high-risk countries [17], it nevertheless appears to be a 

low-incidence country. Egypt had the lowest incidence in the region, 

with 2.9. US SEER incidence was 5.3 for the same years (Table 3.1). 

These rates are 5 to 15 times lower than in Japan, where the overall 

rate is more than 50 [1]. 

The Middle East has better access to fruits and vegetables 

throughout the year than in many places, and the nutritional 

practices have Mediterranean influences. This may result in the low 

incidence rates that were observed. On the other hand, H. pylori

seroprevalence may be high in these countries, but this was not 

reflected in the observed cancer incidence. 
36 MECC Monograph 

Stomach Cancer Chapter 3

Worldwide, the stomach cancer ASR in males is twice that in 

females [1]. Cyprus did not show this pattern; the male-to-female 

ratio was closer to 1 (1.44). Egypt’s ratio was closer to the world 

pattern (1.64), while a ratio close to 2 was observed in Israeli Jews 

and Arabs, Jordanians, and in US SEER. A low male incidence 

rate was especially noticeable in Egypt and may be partially due to 

undiagnosed cases of stomach cancer, especially among the elderly. 

The incidence rates of stomach cancer reported by GLOBOCAN 

[2] for countries in the Middle East (including some MECC 

populations) in 2002 are shown in Table 3.2. The Arab countries in 

the region had low rates, while Israel and Turkey had higher rates. In 

addition, all of the male-to-female rate ratios were lower than 2 for 

Cyprus and the Arab countries, while they were approximately 2 for 

Israel and Turkey. This may be partly due to ethnic differences and 

the more Western lifestyle in Israel and Turkey.

Age

The incidence of stomach cancer rises from age 50 years and is 

highest in the 70-and-older group. The highest incidence in that 

group was in Israeli Jews (121.2 in males; 60.5 in females), and the 

lowest was in Egyptians (17.5 in males; 5.4 in females) (Table 3.1). 

The high incidence in older Israeli Jews, many of whom originated 

from Europe, could be related to the deprived environmental and 

nutritional conditions they suffered during the Second World War. 

This is supported by data showing that Israeli Jews born in Europe 

have a higher stomach cancer incidence than Israeli Jews born 

elsewhere [18]. The low rates in Egypt in this oldest age group, 

among both males and females, strongly suggests that older cases 

have not been diagnosed, perhaps due to elderly patients’ underuse 

of health care services. 

Table 3.1. Stomach Cancer: Number of Cases, Age Distribution, and Age-Standardized Incidence Rates, by Age and Sex, in Cyprus, Israel 

(Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001*

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 198 112 86 3,605 2,169 1,436 177 108 69 206 126 80 687 434 253 9,235 5,541 3,694

Age Groups (Distribution)

<50 y 16.2% 16.1% 16.3% 7.9% 7.1% 9.1% 30.5% 28.7% 33.3% 34.0% 31.0% 38.8% 29.5% 26.5% 34.8% 10.8% 10.8% 10.7%

50-69 y 37.9% 36.6% 39.5% 33.7% 35.9% 30.3% 39.0% 42.6% 33.3% 54.9% 55.6% 53.8% 47.5% 48.6% 45.5% 33.3% 36.7% 28.0%

70+ y 46.0% 47.3% 44.2% 58.4% 56.9% 60.7% 30.5% 28.7% 33.3% 11.2% 13.5% 7.5% 23.0% 24.9% 19.8% 56.0% 52.5% 61.2%

Age Groups (Rates)‡

Total rate 4.9 5.9 4.1 8.5 11.7 6.0 4.6 6.0 3.4 2.9 3.6 2.2 4.8 6.0 3.5 5.3 7.4 3.6

<50 y 1.2 1.4 1.1 1.2 1.3 1.0 1.1 1.2 1.0 0.9 1.0 0.8 1.3 1.4 1.1 0.9 1.0 0.7

50-69 y 14.4 16.4 12.7 26.0 36.3 17.1 13.2 18.5 8.4 10.8 13.3 8.3 15.0 18.5 11.2 16.1 22.5 10.4

70+ y 40.2 54.6 29.0 85.9 121.2 60.5 40.1 52.3 30.7 11.1 17.5 5.4 33.5 48.3 20.1 51.8 75.0 36.1

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Rates are per 100,000 and are age-standardized to the World Standard Million.
 MECC Monograph 37

Stomach Cancer Chapter 3

Histology

According to Table 3.3, the majority of stomach cancers in the 

MECC and US SEER registries were adenocarcinomas. The 

proportion of adenocarcinomas was highest in Cyprus (78.1%) 

and lowest in Egypt (43.9%). According to US SEER data, 

adenocarcinomas comprised 50.1% of the total cases. The second 

most common histologic type in all MECC populations was signet 

ring cell carcinoma. This pattern was the same in the SEER results.

Basis of Diagnosis

The percentage of stomach cancer cases that were microscopically 

confirmed ranged from 80% to 99% (Table 3.3). Stomach cancer is 

among those cancers that are more difficult to detect, and is mostly 

diagnosed at a later stage, often with metastasis to other sites. 

Therefore, the high levels of microscopic confirmation reported in 

Cyprus (99.0%) and Jordan (98.8%) suggest either undercoverage of 

cases by the registries or underdiagnosis by the health care systems. 

Note that the high proportion (96.8%) of microscopically confirmed 

cases in the United States might be expected for a country with a 

highly equipped health care service, but lower proportions would be 

expected for Cyprus and Jordan. Conversely, in Egypt, only 79.6% 

of cases were reported as microscopically confirmed, and this may 

raise questions about the validity of the remaining diagnoses. These 

observations argue for caution in the interpretation of the trends 

discussed in this chapter. 

SUMMARY AND CONCLUSIONS

Among the MECC countries, stomach cancer presents as a larger 

problem in Israel, especially for Israeli Jews. Rates are especially 

low in Egypt, and quite low in Jordan and Cyprus, but the low rates 

may be partly due to underdiagnosis. The lower socioeconomic 

groups who are more prone to stomach cancer due to lifestyle and 

environment may have less access to health care services, and thus 

might be missed in the registration systems because they remain 

undiagnosed or are not hospitalized. Equal access to health care will 

eventually lead to improved reliability in registration records. 

Although H. pylori infection is common in developing countries in 

the Middle East, this is not reflected in the relatively low stomach 

cancer ASRs in these countries. Studies on the effect of H. pylori 

infection in this region and possible interactions with nutritional 

behaviors may give further insight into the etiology of stomach 

cancer in Middle Eastern populations. 

Table 3.2. Stomach Cancer: Age-Standardized 

Incidence Rates,* by Sex, in Middle Eastern 

Countries − 1998-2002

Country Male Female

Cyprus 6.8 4.3

Iraq 4.5 3.8

Israel 12.5 6.9

Jordan 6.6 4.0

Kuwait 4.8 3.0

Lebanon 7.0 4.6

Syrian Arab Republic 7.2 5.5

Turkey 12.2 6.4

*Rates are per 100,000 and are age-standardized to the World Standard Million.

Source: Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence. 

Mortality and prevalence worldwide. IARC cancer base no. 5, version 2.0. Lyon 

(France): IARC Press; 2004.
38 MECC Monograph 

Stomach Cancer Chapter 3

Table 3.3. Stomach Cancer: Number of Cases and Proportions of Microscopic Confirmation and Histologic Type, by Sex, in Cyprus, Israel (Jews and Arabs), 

Egypt, Jordan, and US SEER − 1996-2001*

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases microscopically

confirmed 196 110 86 3,241 1,964 1,277 165 103 62 164 102 62 679 429 250 8,936 5,419 3,517

Microscopically confirmed 99.0% 98.2% 100.0% 89.9% 90.5% 88.9% 93.2% 95.4% 89.9% 79.6% 81.0% 77.5% 98.8% 98.8% 98.8% 96.8% 97.8% 95.2%

Distribution of Microscopically Confirmed Cases

Histologic distribution‡ 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Neoplasm, NOS§ 0.0% 0.0% 0.0% 0.7% 0.4% 1.1% 0.0% 0.0% 0.0% 4.3% 3.9% 4.8% 1.3% 1.2% 1.6% 0.6% 0.5% 0.8%

Carcinoma, NOS§ 0.0% 0.0% 0.0% 4.1% 4.3% 3.9% - 0.0% - - - 0.0% 7.4% 7.2% 7.6% 2.3% 1.9% 2.8%

Carcinoma undifferentiated, NOS§ 0.0% 0.0% 0.0% 0.5% 0.4% 0.6% - - 0.0% 4.9% 3.9% 6.5% 0.6% 0.9% 0.0% 0.2% 0.3% 0.1%

Carcinoma anaplastic, NOS§ 0.0% 0.0% 0.0% 0.9% 0.9% 0.9% - 0.0% - 9.1% 8.8% 9.7% 0.0% 0.0% 0.0% 0.1% - 0.1%

Adenocarcinoma 78.1% 77.3% 79.1% 54.9% 57.6% 50.7% 44.2% 44.7% 43.5% 43.9% 50.0% 33.9% 67.3% 71.6% 60.0% 50.1% 55.1% 42.5%

Intestinal adenocarcinoma 5.6% 7.3% 3.5% 7.4% 7.7% 7.0% 6.1% 6.8% 4.8% 0.0% 0.0% 0.0% 0.9% 0.7% 1.2% 9.1% 9.7% 8.2%

Diffuse carcinoma 5.1% 5.5% 4.7% 0.9% 0.9% 0.9% 1.8% - - 0.0% 0.0% 0.0% 1.5% 1.2% 2.0% 3.6% 3.2% 4.4%

Carcinoid tumor - 0.0% - 1.5% 0.8% 2.4% 6.1% 4.9% 8.1% - - 0.0% 2.2% 1.4% 3.6% 2.6% 1.6% 4.2%

Mucinous adenocarcinoma - 0.0% - 2.3% 2.3% 2.2% 3.6% 3.9% - 6.1% 6.9% 4.8% 1.5% 1.6% 1.2% 1.5% 1.5% 1.5%

Mucin-producing adenocarcinoma - - 0.0% 2.1% 1.8% 2.6% 1.8% 2.9% 0.0% 0.0% 0.0% 0.0% - - 0.0% 1.4% 1.4% 1.3%

Signet ring cell carcinoma 6.6% 5.5% 8.1% 21.0% 18.6% 24.5% 27.9% 28.2% 27.4% 21.3% 17.6% 27.4% 13.5% 10.5% 18.8% 18.0% 15.1% 22.5%

Leiomyosarcoma - - 0.0% 0.3% 0.3% 0.4% 0.0% 0.0% 0.0% 3.0% - 6.5% 0.9% 0.9% - 0.5% 0.4% 0.5%

Gastrointestinal stromal sarcoma - 0.0% - 0.2% 0.3% - - - 0.0% 1.8% - - 0.4% - - 2.6% 2.1% 3.4%

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡The histologic types are included if they are higher than 1% in total in any of the MECC registries; percentages should sum over a column to 100% (with some rounding). Where a percentage has been suppressed because it is based on only 1 or 2 cases, the 

remaining percentages may not sum to 100%.

§NOS indicates “not otherwise specified.”
 MECC Monograph 39

Stomach Cancer Chapter 3

REFERENCES

[1] Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of 25 

major cancers in 1990. Int J Cancer 1999;80:827-41.

[2] Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence. Mortality and prevalence worldwide. IARC cancer base no. 5, 

version 2.0. Lyon (France): IARC Press; 2004.

[3] World Cancer Research Fund and American Institute for Cancer Research. 

Food nutrition and the prevention of cancer: a global perspective. Washington (DC): World Cancer Research Fund; 1997.

[4] Koizumi Y, Tsubono Y, Nakaya N, Kuriyama S, Shibuya D, Matsuoka H, 

et al. Cigarette smoking and the risk of gastric cancer: a pooled analysis of 

two prospective studies in Japan. Int J Cancer 2004;112:1049-55.

[5] Stewart BW, Kleihues P, editors. World cancer report. Lyon (France): 

International Agency for Research on Cancer; 2003.

[6] Ministry of Health. National survey of tobacco, MOH. (Jordan): Ministry 

of Health; 1999.

[7] Ministry of Health. First Israeli National Health and Nutrition SurveyMABAT, 1999-2001. (Israel): Ministry of Health; 2000.

[8] Countrywide Integrated Non Communicable Disease Intervention (CINDI) and Conjunto de Acciones para la Reduccion Multifactorial de las 

Enfermedades No Transmisibles (CARMEN). Survey on tobacco prevention. Cyprus (Italy): World Health Organization; 1998.

[9] Ministry of Health. National survey of tobacco, MOH. (Egypt): Ministry 

of Health; 1998.

[10] Paunder RE. The prevention of H. pylori in different countries. Aliment 

Pharmacol Ther 1995;9:33-40.

[11] Logan RP, Walker MM. Epidemiology and diagnosis of H. pylori infection. Br Med J 2001;323:920-2.

[12] Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, 

Orentreich N, et al. Helicobacter pylori infection and the risk of gastric 

carcinoma. N Engl J Med 1991;325:1127-31.

[13] Gilboa S, Gabay G, Zamir D, Zeev A, Novis B. Helicobacter pylori 

infection in rural settlements (Kibbutzim) in Israel. Int J Epidemiol 

1995;24:232-7.

[14] Niv Y, Niv G, Koren R. 13C-urea breath test for diagnosis of Helicobacter 

pylori infection in the elderly. Dig Dis Sci 2004;49:1840-4.

[15] Fireman Z, Trost L, Kopelman Y, Segal A, Sternberg A. Helicobacter 

pylori: seroprevalence and colorectal cancer. Isr Med Assoc J 2000;2:6-9.

[16] Bani-Hani KE, Hammouri SM. Prevalence of Helicobacter pylori in 

Northern Jordan. Endoscopy based study. Saudi Med J 2001;22:843-7.

[17] Bani-Hani KE, Yaghan RJ, Heis HA, Shatnawi NJ, Matalka II, Bani-Hani 

AM, et al. Gastric malignancies in Northern Jordan with special emphasis 

on descriptive epidemiology. World J Gastroenterol 2004;10:2174-8.

[18] Health.Gov (Israel). Stomach 2001. 2001. Available at: http://www.health.

gov.il/download/sartan/2001/Stomach2.xls. [Last Accessed: 1/06].
40 MECC Monograph 
 MECC Monograph 41

Colorectal Cancer Chapter 4

MICHA BARCHANA

BACKGROUND

Environmental and Lifestyle Risk Factors

Colorectal cancer (CRC) is common in the Western world and 

usually ranks high in incidence and mortality among malignancies 

in those countries. Two observations have led researchers to look 

for diet and lifestyle as explanatory factors of risk for CRC. First, 

ecological studies comparing large populations have shown that 

rates of CRC differ dramatically among countries, varying by as 

much as 10-fold, from low-incidence areas in Asia and Africa, to 

much higher rates in northern Europe and the United States. Second, 

studies have shown that migrants from low-risk areas to high-risk 

Western countries experience rapid increases in CRC risk within the 

same generation [1-5]. Diet appeared to be the major explanatory 

factor for these phenomena: Namely, low consumption of red meat 

and dietary fat and high consumption of fiber in Asian and African 

countries, with an opposite dietary pattern in northern Europe 

and the United States. Recent data, however, do not support an 

association between dietary fiber and risk of CRC [6-8]. Emerging 

data suggest that low levels of physical activity and greater adiposity 

increase risks [9-11]. Since high levels of physical activity and low 

rates of adiposity characterize low-risk countries in general, these 

factors may account for much of the international differences in 

CRC rates. In other studies, cigarette smoking has been associated 

with increased risks of CRC, as has high alcohol consumption. 

These findings were reported in many, although not all, studies, 

and the role of tobacco and alcohol use in the etiology of CRC has 

yet to be determined [12-18]. On the other hand, there are several 

known protecting factors. Nonsteroidal anti-inflammatory drugs, 

in particular aspirin, are thought to be protective [19,20]. Calcium 

supplementation has been shown in randomized studies to reduce 

the recurrence of adenomatous colorectal polyps that are thought to 

be precursors to CRC [21,22]. On the behavioral side, it has been 

shown that physical activity and maintaining a desired body mass 

index may reduce the occurrence of CRC [10,23].

Genetic Risk Factors

The essential element in the etiology of CRC is a process of genetic 

change in the epithelial cells of the colonic mucosa [24,25]. 

Chief among the factors that can initiate CRC development is a 

predisposition to mutagenic effects, where metabolic pathways may 

be altered by polymorphisms in genes responsible for detoxifying 

mutagens. Thus, differences in polymorphisms among individuals 

can account for their differing susceptibility to mutagens from the 

diet. Fecal mutagens in the stool may be produced by the interaction 

of digestion and food products. Changes in the fecal microflora 

indicate that changes in diet may alter mutagenic activity by altering 

extracellular superoxide formation [26]. 

Family history – the occurrence of CRC in a first- or second-degree 

relative – is an identified risk factor for CRC. An increased risk 

among siblings of an affected person has been observed, and in one 

study was particularly high for cancer in the proximal colon (from 

the cecum up to the distal third of the transverse colon) [27]. An 

increased risk has also been observed among children of affected 

persons, both for CRC overall and for cancers of the proximal colon, 

distal colon, and rectum, with relative risks of approximately 1.8 

[28].

People affected with inflammatory bowel disease, either Crohn’s 

disease or ulcerative colitis, are at increased risk for developing 

cancers of the gastrointestinal tract, particularly CRC [29]. The 

current literature suggests that these persons have a genetic 

predisposition to CRC and that long-standing inflammation is not of 

primary importance in the promotion of cancer [30-34]. 
42 MECC Monograph 

Colorectal Cancer Chapter 4

Familial polyposis syndromes are characterized by the early onset 

of multiple polyps and a very high risk of CRC development [35]. 

These syndromes have autosomal dominant inheritance with high 

but variable penetrance. Hereditary nonpolyposis colon cancer 

(HNPCC) syndrome is inherited as an autosomal dominant trait with 

high penetrance. Its phenotypic features are early-onset CRC (mean 

age: 46 years), multiple synchronous or metachronous CRCs (35%), 

and CRCs usually, but not always, located in the proximal colon 

[36]. HNPCC cancers are more likely to be signet-ring cancers 

and poorly differentiated, with extensive inflammatory infiltrates 

[37,38]. Particularly relevant to this MECC report is the feature of 

inherited CRC in Ashkenazi Jews (Jews of European origin). Israeli 

Ashkenazi Jews have the highest CRC incidence of any Israeli 

ethnic group. There are reports of a missense mutation (I1307K) 

in the APC gene, unique to Ashkenazi Jews and found in 6% of the 

Ashkenazi Jewish population and in 28% of those in this population 

with a family history of CRC. Among the carriers of the mutation, 

CRC is found in 13% of those who have polyps [39,40]. There do 

not appear to be any differences in clinical presentation between 

carriers of the mutation and noncarriers, so genetic testing in this 

population may be required to identify high-risk individuals for 

screening. 

Early Detection

CRCs are among the very few cancer sites where screening and 

early detection are both feasible and proven to reduce mortality. The 

recommended test for mass screening is the fecal occult blood test 

(FOBT), which has been extensively studied and used since the early 

1980s. This test, which acts as a first screen for possible malignancy, 

is designed to detect blood traces in the stool on a guaiac-based 

testing sample. Persons testing positive usually undergo colonoscopy 

as a more invasive but definitive examination. Newer technologies 

combine the guaiac-based test with tests based on molecular biology 

to look for cancer biomarkers in the stool. Serial guaiac-based FOBT 

is simple, inexpensive, and proven effective at reducing mortality 

from CRC. Immunochemical FOBT facilitates compliance and 

offers improved specificity, but at increased cost relative to guaiacbased FOBT. Fecal DNA testing may provide enhanced sensitivity 

for detection of CRC compared with FOBT, but its high cost limits 

its use for generalized screening. Other noninvasive tests, such as 

rectal mucin testing, have been developed more recently and require 

evaluation and comparison with guaiac-based FOBT. Serum tests, 

such as proteomics, nuclear matrix proteins, and serum DNA, are 

still in their infancy but remain a hope for the future [41-46].

More direct methods for detecting colonic premalignant and 

malignant tumors include the use of colonoscopy or flexible 

sigmoidoscopy [47,48]. An exciting new CRC screening option is 

virtual colonoscopy (VC), which, by screening out persons without 

neoplasia, allows colonoscopy to be reserved for those requiring 

therapeutic intervention. The sensitivity of VC for large adenomas 

and CRC appears to be high, although results vary by center, and 

sensitivity for small adenomas is low. Some investigators have 

suggested that VC might be a useful option for investigating patients 

who test positive with stool-based screening tests [49-51]. Because 

no CRC screening technology program has been implemented in a 

substantial proportion of any MECC population, screening has yet to 

reduce the incidence or mortality of CRC in the Middle East. 

Worldwide Incidence

Globally, the age-standardized incidence rate (ASR) of CRC is 20.1 

per 100,000 males and 14.6 per 100,000 females. As mentioned 

earlier, there are notable differences between CRC incidence rates 

in more developed versus less developed countries. In the developed 

parts of the world, the ASR is 40.0 in males and 26.6 in females; 

in less developed areas, the rates are 10.2 and 7.7, respectively. 

The highest ASRs in males are observed in Australia/New Zealand 

(48.2), followed by North America (44.4) and Western Europe 

(42.9). At the other end of the scale, the rates in South-Central Asia 

(4.7) and Central Africa (2.3) are lowest [52].

Incidence-to-mortality ratios also differ substantially between 

developed and less developed countries. The rate ratio varies from 

2.9 in North America (indicating 2.9 incident cases for every death 
 MECC Monograph 43

Colorectal Cancer Chapter 4

from CRC) to 1.0 in Central and North Africa (indicating that for 

every new case of CRC, there is a death from this cancer) [52].

The pattern of CRC incidence rates in females is similar to that 

in males, with the Australian continent presenting the highest rate 

(36.9), followed by North America (32.9). The lowest CRC rates 

in females are found throughout Africa (3.3-4.0), except South 

Africa, and also in South-Central Asia (3.5). Incidence-to-mortality 

rate ratios are high in North America and Australia (2.8 and 2.6, 

respectively) and low in all African countries (1.07-1.10), except 

South Africa [52].

RESULTS

The total number of CRC cases reported to the registries during 

the study period was 74,369: 455 cases in Egyptians, 550 in Israeli 

Arabs, 697 in Cypriots, 1,654 in Jordanians, 15,533 in Israeli Jews, 

and 55,480 in US SEER (see Table 1.5). 

Data Quality Indices

The gold standard for defining a cancer is the microscopic proof 

of malignant cells. Cancer registries rely, for the most part, on 

histological or cytological reports when defining incident cases. 

However, cancer registries collect information from other sources, 

such as death notifications and imaging procedures, that can supply 

information of lesser accuracy on the disease. The percentage of 

microscopically confirmed cases is often used as a quality indicator. 

Another way to assess quality of data is through the coding of 

subsites. The coding system adopted by MECC countries, the 

International Classification of Diseases in Oncology (ICD-O) (3rd

edition), is based, for CRCs, on the anatomic location of the lesion, 

and reserves a code for a more general definition: “Colon, not 

otherwise specified (NOS).” This term is usually reserved for those 

cases where the exact location of the tumor cannot be accurately 

defined. The percentage of use of this more general code can also be 

used as a measure of accuracy. 

Table 4.1 shows the percentage of microscopically confirmed total 

cases and the percentage of cases coded “Colon, NOS” for each of 

the populations. 

The percentage of microscopic confirmation of CRC varied between 

84.6% (Egypt) and 99.0% (Cyprus and Jordan). The higher values 

correspond to registries that do active registration where patient data 

and records are easily accessed for further exploration, but a very 

high value may also indicate that death certificates are not used, 

which would result in underestimated incidence rates. The US SEER 

microscopic confirmation rate was high (97.5%), but SEER has an 

Table 4.1. Colorectal Cancer: Proportions of Total Cases Microscopically Confirmed and of Cases Coded “Colon, NOS”* 

in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US 

SEER − 1996-2001

Registry Proportion Microscopically Confirmed Proportion Colon, NOS*

Cyprus 

1998-2001 99.0% 20.1%

Israel (Jews) 

1996-2001 91.4% 17.7%

Israel (Arabs) 

1996-2001 91.5% 17.8%

Egypt 

1999-2001 84.6% 23.1%

Jordan 

1996-2001 99.0% 35.9%

US SEER†

1999-2001 97.5% 2.9%

*NOS indicates “not otherwise specified.”

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
44 MECC Monograph 

Colorectal Cancer Chapter 4

active follow-up program to check cases that are initially found by 

death certificate. 

The percentage of cases coded “Colon, NOS” was 20.1% for 

Cypriots, 17.7% for Israeli Jews, 17.8% for Israeli Arabs, 23.1% 

for Egyptians, 35.9% for Jordanians, and 2.9% for US SEER (Table 

4.1). A large proportion of cases coded in this less accurate way can 

result in less accurate data, although it should not greatly impact the 

estimates of overall incidence of CRC. 

Overall Rates

As mentioned earlier, CRC is one of the most common cancers in the 

Western world, and constitutes about 13% of all cancers occurring in 

these countries. In MECC countries, CRC in Israeli Jews constituted 

14.8% of all new cases in this population, followed by Cypriots and 

US SEER, where it was approximately 11% of all new cancer cases. 

Among Israeli Arabs and Jordanians, only approximately 9% of 

cancers were CRC, and in Egypt, 4.4%. (See Table 1.6.) 

Observing the incidence rate of CRC (Table 4.2), we can subdivide 

the MECC countries into high-, middle-, and low-incidence 

countries. Israeli Jews had the highest incidence rate among all the 

populations considered (36.9). The ASR for Israeli Jewish males was 

41.7, followed by US males (37.7), Israeli Jewish females (33.3), 

and US females (27.4). Cypriots had a lower incidence rate (17.3), 

similar to that of Israeli Arabs (15.2). Jordanians and Egyptians 

presented the lowest rates: 11.3 and 6.0, respectively. 

The male-to-female incidence rate ratio (IRR) is another 

characteristic of CRC patterns. In developed countries, the maleto-female IRR tends to about 1.5, and in less developed countries 

it is about 1.3 [52]. In the MECC data, the IRR was 1.38 for US 

SEER, 1.35 for Egyptians, 1.27 for Israeli Arabs, 1.25 for Israeli 

Jews, 1.19 for Cypriots, and 1.03 for Jordanians. These findings 

do not completely follow the general trend of higher IRRs in more 

developed countries (Table 4.2)

Table 4.2. Colorectal Cancer: Number of Cases and Age-Standardized Incidence Rates,* by Age and Sex, in Cyprus, Israel, Egypt, Jordan, 

and US SEER − 1996-2001†

Cyprus Israel (Jews) Israel (Arabs) Egypt Jordan US SEER‡

1998-2001 1996-2001 1996-2001 1999-2001 1996-2001 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 697 355 342 15,533 7,805 7,728 550 287 263 455 261 194 1,654 845 809 55,480 27,892 27,588

Total rate* 17.3 19.0 16.0 36.9 41.7 33.3 15.2 17.3 13.6 6.0 6.9 5.1 11.3 11.5 11.2 32.0 37.7 27.4

<40 y 1.2 1.2 1.1 1.0 1.0 1.1 1.0 0.7 1.4 1.4 1.7 1.1 1.2 1.1 1.2 1.2 1.3 1.2

40-59 y 20.1 17.6 22.7 40.5 38.9 42.0 21.6 22.6 20.6 13.3 13.4 13.1 20.9 18.4 23.7 37.9 43.3 32.8

60-69 y 84.5 96.6 73.8 181.1 210.6 156.9 76.4 80.2 73.1 19.6 27.2 12.4 52.6 54.0 51.0 154.0 185.4 126.4

70+ y 159.2 193.4 132.3 374.0 451.5 318.4 116.5 161.2 80.0 20.8 25.1 17.1 60.7 78.6 44.4 311.3 369.8 270.8

*Rates are per 100,000 and are age-standardized to the World Standard Million.

†”[Numeral]” (italic) = 0 or 3-15 cases.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
 MECC Monograph 45

Colorectal Cancer Chapter 4

Colon versus Rectal Cancers

The MECC project focuses on cross-sectional data collection and 

does not include data on trends of the disease. Data on secular trends 

in CRC incidence emphasize the different behavior of cancers of 

the colon and rectum. Colon cancer incidence has been rising in the 

last decade in many developed and developing countries, and rectal 

cancer incidence has been falling. The pattern of CRC site incidence 

in industrialized and “Westernized” countries is that of a decrease 

in rectal cancer and an increase in proximal colon cancer. This has 

been noted worldwide in diverse populations [53-68]. The United 

States has the unique pattern of a decreasing incidence of total 

CRC and distal (left-sided) CRC, but a stable incidence of proximal 

right-sided CRC [69]. In many countries, the increase in proximal 

CRC has been noted to be more prominent in females [70]. Norway 

and Denmark are exceptional because distal is more prominent than 

proximal CRC in these countries [67,71]. Reasons for the changing 

CRC trends and the epidemiology of the CRC site distribution are 

assumed to be related to changes in diet and lifestyle associated with 

industrialization [56]. Worldwide, industrialization is associated 

with an increasing life expectancy, especially among females, and 

there is now a substantially increased proportion of females who are 

older than 65 years [38,72]. However, the reason for their greater 

tendency to develop proximal cancer is unclear.

Table 4.3 shows the colon-to-rectal cancer IRR in some selected 

countries [73] and for MECC populations for the years 1993-

1997. According to the above theory, industrialized countries 

would tend to have more colon cancer and less rectal cancer, and 

therefore higher colon-to-rectal cancer IRRs. The table shows that 

the MECC populations did not follow this pattern, with Egyptians 

and Jordanians (less industrialized populations) having IRRs only 

a little lower than those of US SEER Whites, and higher than those 

in China and Poland. However, Israeli Jews (a more industrialized 

population) did have a high IRR. 

Subsites of Colorectal Cancer

Proportions of cases diagnosed by anatomic location within the 

colon (excluding the rectum) are presented in Figure 4.1. It is 

difficult to interpret the data from Egypt and Jordan because a 

substantial proportion of the cases are coded “Colon, NOS.” The 

proportion of ascending colon cancer appears similar in the United 

States and Israel and accounts for about 15% of all colon cancers, 

whereas in Cyprus, ascending colon cancer accounts for about 5% of 

cases. Cancers of the cecum occur in greater proportions in Cyprus 

and the United States (15% and 21%, respectively) than in Israel 

(less than 10%). The sigmoid colon is involved in about 30% of 

Table 4.3: Colorectal Cancer: Age-Standardized Incidence Rates* 

and Incidence Rate Ratios (IRR) of Colon and Rectal Cancers in 

Selected Countries and in Cyprus, Israel (Jews and Arabs), Egypt, 

Jordan, and US SEER − 1993-1997

Country/Registry

Male Female

Colon Rectum IRR Colon Rectum IRR

Canada 25.7 15.8 1.6 19.8 8.8 2.2

China - Shanghai 11.5 9.0 1.3 12.0 7.5 1.6

Japan - Osaka 24.7 15.1 1.6 15.5 7.3 2.1

Denmark 20.5 17.6 1.2 18.4 11.2 1.6

Poland - Krakow 14.5 11.7 1.2 10.4 6.9 1.5

Cyprus 12.7 6.3 2.0 11.2 4.8 2.3

Israel (Jews) 29.6 12.1 2.4 24.7 8.6 2.9

Israel (Arabs) 10.5 6.8 1.5 9.4 4.2 2.2

Egypt 4.6 2.3 2.0 3.3 1.8 1.8

Jordan 7.6 3.9 1.9 7.2 4.0 1.8

US SEER (Whites) 25.9 13.0 2.0 19.6 8.2 2.4

US SEER (Blacks) 32.3 12.7 2.5 26.0 8.2 3.2

*Rates are per 100,000 and are age-standardized to the World Standard Million.

Source: Parkin, D. M., Whelan, S. L., Ferlay, J., Teppo, L., and eds. Cancer incidence in five continents, volume VIII. Lyon 

(France): International Agency for Research on Cancer; 2002. IARC Scientific Publication No. 155.
46 MECC Monograph 

Colorectal Cancer Chapter 4

colon cancers in Cypriots, Israeli Jews and Arabs, and US SEER. 

Cancers involving the transverse colon occur in about the same 

proportion in the Israeli populations and in Cypriots (4% to 5%), 

but the proportion is higher in US SEER (about 9%). In Israel, the 

percentage of descending colon cancers is somewhat higher (8%) 

than in US SEER and Cyprus (6% and 4%, respectively). 

Age-Specific Incidence Rates

CRC is rare under 40 years of age, and rates begin to rise sharply 

after this age. By the age of 40 to 59 years, Israeli Jews and the US 

SEER population had a substantially higher rate (about 40) than the 

other populations (13 to 22). The same pattern, with Israeli Jews 

and US SEER having the highest age-specific rates, occurred in 

all age groups over 40 years (Table 4.2). Figure 4.2 presents the 

pattern graphically, showing ASRs by 5-year age groups for ages 50 

years and above. Rates in Israeli Jews and the US SEER population 

display a sharp rise with age, while rates in the other populations 

increase with age more slowly. In fact, rates remain almost 

invariable from the age of 50 years in Egyptians, who have very low 

rates. In Jordanians and Israeli Arabs, the rates rise by about 20% 

and 40%, respectively, for each 5-year period between the ages of 50 

and 75 years. In Cypriots, the percentage rise per 5-year period over 

this age range is about 50%, which is the same as the rise in Israeli 

Jews and US SEER. However, because the Cypriot rate at age 50-54 

years is about half that of Israeli Jews and the US SEER population, 

the 50% rise in the Cypriot rate constitutes a much smaller increase. 

SUMMARY AND CONCLUSIONS

The comparison of incidence rates among several Middle Eastern 

populations provides the opportunity to explore one of the most 

significant types of cancer in a new perspective. The comparison 

comprises 4 countries and 5 subpopulations situated in close 

proximity that have some similarities and also some marked 

differences in lifestyle. Egypt and Jordan are classified by the 

World Bank [74] as developing countries, while Cyprus and Israel 

are considered developed countries. The data presented support 

the existence of a link between economic status and CRCs, where 

higher rates were observed in Israeli Jews (similar to US rates) 

and, to a lesser extent, in Cypriots. The burden of CRC was high 

among Israeli Jews (higher even than in the United States), and other 

published data show very high rates among Israeli Jews originating 

from European countries [70]. The high socioeconomic status and 

the elevated rate of genetic mutations and polymorphisms in this 

subpopulation are probably both factors related to the increased 

incidence of CRC. The very low incidence of CRC in Egypt might 

be explained by other competing diseases (e.g., carcinoma of the 

urinary bladder), low detection rates, or local nutritional factors that 

are protective. 

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

 Cyprus 

1988-2001

Israel (Jews) 

1996-2001

 Israel (Arabs) 

1996-2001

 Egypt 

1999-2001

 Jordan 

1996-2001

 US SEER*

1999-2001

 Cecum Appendix Ascending Colon

 Hepatic Flexure Transverse Colon Splenic Flexure

 Descending Colon Sigmoid Colon Colon, NOS†

Figure 4.1. Colorectal Cancer: Proportions of Colon Cancers Diagnosed in Different Anatomical 

Subsites in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER � 1996-2001

*SEER 13 Registries, Public Use Data, from data submitted November 2004.

†NOS indicates not otherwise specified.
 MECC Monograph 47

Colorectal Cancer Chapter 4

0

50

100

150

200

250

300

350

400

450

500

50-54 55-59 60-64 65-69 70-74 75+

Cyprus

Israel (Jews)

Israel (Arabs)

Egypt

Jordan

US SEER*

Rate/100,000

Age group

Figure 4.2. Colorectal Cancer: Age-Specific Incidence Rates in 5-Year Age Groups for Ages 50 Years

and Older in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER � 1996-2001

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
48 MECC Monograph 

Colorectal Cancer Chapter 4

Colon cancer was more common than rectal cancer in all the MECC 

populations studied, and it constituted over 65% of all CRCs. 

Examination of the rates of proximal and distal cancers confirms 

the pattern of a greater proportion of proximal cancers in the more 

industrialized populations. 

This comparison can add to the already established observation 

that CRC is mainly a result of lifestyle and behavior, including 

diet and body mass. The correlation found in this comparison 

between CRC incidence and level of economic development of 

the various populations is consistent with published literature that 

more developed countries present with higher rates. It would be 

interesting to conduct further research in this direction, especially to 

study in greater depth the apparently low incidence rates presented 

for Egypt.

REFERENCES

76,947 women and 47,279 men. Cancer Epidemiol Biomarkers Prev 

2005;14:842-9.

[8] Campos FG, Logullo Waitzberg AG, Kiss DR, Waitzberg DL, Habr-Gama 

A, Gama-Rodrigues J. Diet and colorectal cancer: current evidence for 

etiology and prevention. Nutr Hosp 2005;20:18-25.

[9] Steindorf K, Jedrychowski W, Schmidt M, Popiela T, Penar A, Galas 

A, et al. Case-control study of lifetime occupational and recreational 

physical activity and risks of colon and rectal cancer. Eur J Cancer Prev 

2005;14:363-71.

[10] Samad AK, Taylor RS, Marshall T, Chapman MA. A meta-analysis of the 

association of physical activity with reduced risk of colorectal cancer. 

Colorectal Dis 2005;7:204-13.

[11] Cerin E, Leslie E, Bauman A, Owen N. Levels of physical activity for 

colon cancer prevention compared with generic public health recommendations: population prevalence and sociodemographic correlates. Cancer 

Epidemiol Biomarkers Prev 2005;14:1000-2.

[12] Correa Lima MP, Gomes-da-Silva MH. Colorectal cancer: lifestyle and 

dietary factors. Nutr Hosp 2005;20:235-41.

[13] Zimmerman DD, Gosselink MP, Mitalas LE, Delemarre JB, Hop WJ, 

Briel JW, et al. Smoking impairs rectal mucosal bloodflow – a pilot study: 

possible implications for transanal advancement flap repair. Dis Colon 

Rectum 2005;48:1228-32.

[14] Luchtenborg M, Weijenberg MP, Kampman E, van Muijen GN, Roemen 

GM, Zeegers MP, et al. Cigarette smoking and colorectal cancer: APC 

mutations, hMLH1 expression, and GSTM1 and GSTT1 polymorphisms. 

Am J Epidemiol 2005;161:806-15.

[15] Perez-Holanda S, Rodrigo L, Vinas-Salas J, Pinol-Felis C. Effect of 

ethanol consumption on colon cancer in an experimental model. Rev Esp 

Enferm Dig 2005;97:87-96.

[16] Chen K, Jiang Q, Ma X, Li Q, Yao K, Yu W, et al. Alcohol drinking and 

colorectal cancer: a population-based prospective cohort study in China. 

Eur J Epidemiol 2005;20:149-54.

[17] Yeh CC, Hsieh LL, Tang R, Chang-Chieh CR, Sung FC. Vegetable/fruit, 

smoking, glutathione S-transferase polymorphisms and risk for colorectal 

cancer in Taiwan. World J Gastroenterol 2005;11:1473-80.

[18] Larsson SC, Giovannucci E, Wolk A. A prospective study of dietary folate 

intake and risk of colorectal cancer: modification by caffeine intake and 

[1] Nilsson B, Gustavson-Kadaka E, Rotstein S, Hakulinen T, Rahu M, Aareleid T. Cancer incidence in Estonian migrants to Sweden. Int J Cancer 

1993;55:190-5.

[2] Monroe KR, Hankin JH, Pike MC, Henderson BE, Stram DO, Park S, et 

al. Correlation of dietary intake and colorectal cancer incidence among 

Mexican-American migrants: the multiethnic cohort study. Nutr Cancer 

2003;45:133-47.

[3] Wogan GN. Diet and nutrition as risk factors for cancer. Princess Takamatsu Symp 1985;16:3-10.

[4] Levin KE, Dozois RR. Epidemiology of large bowel cancer. World J Surg 

1991;15:562-7.

[5] Kune S, Kune GA, Watson L. The Melbourne colorectal cancer study: 

incidence findings by age, sex, site, migrants and religion. Int J Epidemiol 

1986;15:483-93.

[6] Tsubono Y, Otani T, Kobayashi M, Yamamoto S, Sobue T, Tsugane S. 

No association between fruit or vegetable consumption and the risk of 

colorectal cancer in Japan. Br J Cancer 2005;92:1782-4.

[7] Michels KB, Fuchs CS, Giovannucci E, Colditz GA, Hunter DJ, Stampfer MJ, et al. Fiber intake and incidence of colorectal cancer among 
 MECC Monograph 49

Colorectal Cancer Chapter 4

cigarette smoking. Cancer Epidemiol Biomarkers Prev 2005;14:740-3.

[19] Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan 

GC, Fuchs CS. Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA 2005;294:914-23.

[20] Courtney ED, Melville DM, Leicester RJ. Review article: chemoprevention of colorectal cancer. Aliment Pharmacol Ther 2004;19:1-24.

[21] Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane 

Database Syst Rev 2005;CD003548.

[22] Pence BC. Role of calcium in colon cancer prevention: experimental and 

clinical studies. Mutat Res 1993;290:87-95.

[23] Chao A, Connell CJ, Jacobs EJ, McCullough ML, Patel AV, Calle EE, et 

al. Amount, type, and timing of recreational physical activity in relation 

to colon and rectal cancer in older adults: the Cancer Prevention Study II 

Nutrition Cohort. Cancer Epidemiol Biomarkers Prev 2004;13:2187-95.

[24] Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert 

M, et al. Genetic alterations during colorectal-tumor development. N Engl 

J Med 1988;319:525-32.

[25] Winawer SJ, Shike M. Dietary factors in colorectal cancer and their possible effects on earlier stages of hyperproliferation and adenoma formation. J Natl Cancer Inst 1992;84:74-5.

[26] Winters MD, Schlinke TL, Joyce WA, Glore SR, Huycke MM. Prospective case-cohort study of intestinal colonization with enterococci that 

produce extracellular superoxide and the risk for colorectal adenomas or 

cancer. Am J Gastroenterol 1998;93:2491-500.

[27] Hemminki K, Chen B. Familial risk for colorectal cancers are mainly due 

to heritable causes. Cancer Epidemiol Biomarkers Prev 2004;13:1253-6.

[28] Marchand LL. Combined influence of genetic and dietary factors on 

colorectal cancer incidence in Japanese Americans. J Natl Cancer Inst 

Monogr 1999;101-5.

[29] Lichtenstein GR. Reduction of colorectal cancer risk in patients with 

Crohn’s disease. Rev Gastroenterol Disord 2002;2:S16-S24.

[30] Riegler G, Carratu R, Tartaglione M, Morace F, Manzione R, Arimoli 

A. Prevalence and relative risk of malignancy in relatives of inflammatory bowel disease patients and control subjects. J Clin Gastroenterol 

1998;27:211-4.

[31] Jain SK, Peppercorn MA. Inflammatory bowel disease and colon cancer: a 

review. Dig Dis 1997;15:243-52.

[32] Itzkowitz SH. Inflammatory bowel disease and cancer. Gastroenterol Clin 

North Am 1997;26:129-39.

[33] Itzkowitz SH, Yio X. Inflammation and cancer IV. Colorectal cancer in 

inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol 2004;287:G7-17.

[34] Rhodes JM, Campbell BJ. Inflammation and colorectal cancer: IBD-associated and sporadic cancer compared. Trends Mol Med 2002;8:10-6.

[35] Bussey HJR. Historical developments in familial polyposis. In: Herrera 

L, editor. Familial adenomatous polyposis. New York (NY): Alan R. Liss; 

1990. p. 1-7.

[36] Peltomaki P, De la Chapelle A. Mutations predisposing to hereditary nonpolyposis colorectal cancer. Adv Cancer Res 1997;71:93-119.

[37] Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch JF, Lynch PM, et al. 

Genetics, natural history, tumor spectrum, and pathology of hereditary 

nonpolyposis colorectal cancer: an updated review. Gastroenterology 

1993;104:1535-49.

[38] Bonita R, Howe AL. Older women in an aging world: achieving health 

across the life course. World Health Stat Q 1996;49:134-41.

[39] Prior TW, Chadwick RB, Papp AC, Arcot AN, Isa AM, Pearl DK, et al. 

The I1307K polymorphism of the APC gene in colorectal cancer. Gastroenterology 1999;116:58-63.

[40] Rozen P, Shomrat R, Strul H, Naiman T, Karminsky N, Legum C, et 

al. Prevalence of the I1307K APC gene variant in Israeli Jews of differing ethnic origin and risk for colorectal cancer. Gastroenterology 

1999;116:54-7.

[41] Menges M, Gartner B, Georg T, Fischinger J, Zeitz M. Cost-benefit analysis of screening colonoscopy in 40- to 50-year-old first-degree relatives of 

patients with colorectal cancer. Int J Colorectal Dis 2005;[Epub]:1-6.

[42] Lindberg J, Stenling R, Palmqvist R, Rutegard J. Efficiency of colorectal 

cancer surveillance in patients with ulcerative colitis: 26 years’ experience 

in a patient cohort from a defined population area. Scand J Gastroenterol 

2005;40:1076-80.

[43] Losi L, Di Gregorio C, Pedroni M, Ponti G, Roncucci L, Scarselli A, et al. 

Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer 

syndromes. Am J Gastroenterol 2005;100:2280-7.

[44] Hakama M, Hoff G, Kronborg O, Pahlman L. Screening for colorectal 

cancer. Acta Oncol 2005;44:425-39.
50 MECC Monograph 

Colorectal Cancer Chapter 4

[45] Janssens JF. Faecal occult blood test as a screening test for colorectal 

cancer. Acta Gastroenterol Belg 2005;68:244-6.

[46] Yang SH, Chien CC, Chen CW, Li SY, Huang CJ. Potential of faecal RNA 

in diagnosing colorectal cancer. Cancer Lett 2005;226:55-63.

[47] Janssens JF. Flexible sigmoidoscopy as a screening test for colorectal 

cancer. Acta Gastroenterol Belg 2005;68:248-9.

[48] Atkin W. Options for screening for colorectal cancer. Scand J Gastroenterol Suppl 2003;13-6.

[49] Ouyang DL, Chen JJ, Getzenberg RH, Schoen RE. Noninvasive testing 

for colorectal cancer: a review. Am J Gastroenterol 2005;100:1393-403.

[50] Bromer MQ, Weinberg DS. Screening for colorectal cancer – now and the 

near future. Semin Oncol 2005;32:3-10.

[51] Autier P, Boyle P, Buyse M, Bleiberg H. Is FOB screening really the answer for lowering mortality in colorectal cancer? Recent Results Cancer 

Res 2003;163:254-63.

[52] Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence. Mortality and prevalence worldwide. IARC cancer base no. 5, 

version 2.0. Lyon (France): IARC Press; 2004.

[53] Slater G, Papatestas AE, Tartter PI, Mulvihill M, Aufses AH, Jr. Age 

distribution of right- and left-sided colorectal cancers. Am J Gastroenterol 

1982;77:63-6.

[54] Vobecky J, Leduc C, Devroede G. Sex differences in the changing anatomic distribution of colorectal carcinoma. Cancer 1984;54:3065-9.

[55] Jensen OM. Different age and sex relationship for cancer of subsites of 

the large bowel. Br J Cancer 1984;50:825-9.

[56] Schub R, Steinheber FU. Rightward shift of colon cancer. A feature of the 

aging gut. J Clin Gastroenterol 1986;8:630-4.

[57] Jass JR. Subsite distribution and incidence of colorectal cancer in New 

Zealand, 1974-1983. Dis Colon Rectum 1991;34:56-9.

[58] Kee F, Wilson RH, Gilliland R, Sloan JM, Rowlands BJ, Moorehead RJ. 

Changing site distribution of colorectal cancer. BMJ 1992;305:158.

[59] Demers RY, Severson RK, Schottenfeld D, Lazar L. Incidence of colorectal adenocarcinoma by anatomic subsite. An epidemiologic study of 

time trends and racial differences in the Detroit, Michigan area. Cancer 

1997;79:441-7.

[60] Ji BT, Devesa SS, Chow WH, Jin F, Gao YT. Colorectal cancer incidence 

trends by subsite in urban Shanghai, 1972-1994. Cancer Epidemiol Biomarkers Prev 1998;7:661-6.

[61] Bonithon-Kopp C, Benhamiche AM. Are there several colorectal cancers? 

Epidemiological data. Eur J Cancer Prev 1999;8:S3-12.

[62] Troisi RJ, Freedman AN, Devesa SS. Incidence of colorectal carcinoma 

in the U.S.: an update of trends by gender, race, age, subsite, and stage, 

1975-1994. Cancer 1999;85:1670-6.

[63] Miller A, Gorska M, Bassett M. Proximal shift of colorectal cancer in the 

Australian Capital Territory over 20 years. Aust N Z J Med 2000;30:221-

5.

[64] Mitry E, Benhamiche AM, Couillault C, Roy P, Faivre-Finn C, Clinard 

F, et al. Effect of age, period of diagnosis and birth cohort on large bowel 

cancer incidence in a well-defined French population, 1976-1995. Eur J 

Cancer Prev 2002;11:529-34.

[65] Cucino C, Buchner AM, Sonnenberg A. Continued rightward shift of 

colorectal cancer. Dis Colon Rectum 2002;45:1035-40.

[66] Takada H, Ohsawa T, Iwamoto S, Yoshida R, Nakano M, Imada S, et al. 

Changing site distribution of colorectal cancer in Japan. Dis Colon Rectum 2002;45:1249-54.

[67] Thygesen LC, Gronbaek M, Johansen C. Colorectal cancer in Denmark 

1943-1997. Dis Colon Rectum 2004;47:1232-41.

[68] Rabeneck L, Davila JA, El Serag HB. Is there a true “shift” to the 

right colon in the incidence of colorectal cancer? Am J Gastroenterol 

2003;98:1400-9.

[69] White JS, McCallion K, Gardiner KR, Watson RG, Collins JS, McKee 

F, et al. Changing patterns of colorectal cancer. Am J Gastroenterol 

2004;99:766.

[70] Ministry of Health. Israel National Cancer Registry. 2005. Available at: 

http://www.health.gov.il/icr/. [Last Accessed: 1/06].

[71] Imperiale TF, Wagner DR, Lin CY, Larkin GN, Rogge JD, Ransohoff DF. 

Risk of advanced proximal neoplasms in asymptomatic adults according 

to the distal colorectal findings. N Engl J Med 2000;343:169-74.

[72] Maddox M. Older women and the meaning of health. J Gerontol Nurs 

1999;25:26-33.

[73] Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in 

five continents, volume VIII. IARC Scientific Publication No. 155. Lyon 

(France): International Agency for Research on Cancer; 2002.

[74] The World Bank. Data & statistics: country classification. 2006. Available 

at: http://www.worldbank.org/data/countryclass/classgroups.htm. [Last 

Accessed: 1/06].
 MECC Monograph 51

Liver and Intrahepatic Bile Duct Cancer Chapter 5

AMAL SAMY IBRAHIM

BACKGROUND

Incidence and Prevalence

Hepatocellular carcinoma (HCC), which is the main pathological 

subtype of liver cancer, is a major contributor to cancer incidence 

and mortality. There is wide variation in the global distribution of 

HCC. Countries in Asia and sub-Saharan Africa bear 80% of the 

burden. Because of its short survival and high fatality rates, the 

incidence, prevalence, and mortality rates for HCC are very close to 

one another.

For Asian males, the highest age-standardized incidence rate (ASR) 

published in Cancer Incidence in Five Continents [1] reached 95.7 

per 100,000 in Quidong County, China. In countries other than those 

in East and Southeast Asia, rates as low as 1.4 among Israelis born 

in Israel were reported. The median ASR in Asia was 17.1, reported 

from Miyagi Prefecture, Japan (Table 5.1).

In other continents, the median ASR for males was 5.5 for Europe 

(Tyrol, Austria), 4.6 in North America (New Jersey, United States), 

3.8 in Oceania (New Zealand), and 3.5 in South America (Villa 

Clara, Cuba). In Africa, unusually, the two populations ranked in 

the middle of the distribution had very different rates: In Harare, 

Zimbabwe, the rate was 27.9, and the next lowest rate was in 

Kyadondo, Uganda (6.5). Worldwide, the median ASR for all 

registries was 5.4, among Blacks in New Jersey, United States of 

America [1]. Independent of race and geography, rates in men are at 

least 2 to 3 times those in women. This sex ratio is more pronounced 

in high-risk regions [2]. 

In the United States, the incidence of HCC has approximately 

doubled over the past 3 decades. Registry data in Canada and 

Western Europe show similar trends. In contrast, the incidence of 

HCC in Singapore and Shanghai, China, both high-risk regions, has 

declined steadily over the past 2 decades. Reasons for both trends 

are not completely understood, but are likely related to public health 

efforts to control hepatitis B virus (HBV) in Asia and the “new” risk 

factors such as hepatitis C virus (HCV) and, possibly, diabetes in 

low-risk countries [3]. 

Risk Factors

In most countries where the risk is high for liver cancer, principal 

risk factors include infection with HBV and exposure to dietary 

aflatoxin. In contrast, HCV and alcohol consumption are more 

important risk factors in low-risk countries. In countries with low 

liver cancer ASRs, excessive alcohol intake, cigarette smoking, and 

oral contraceptive use also are risk factors for HCC [4].

Hepatitis B virus. Chronic infection by HBV is by far the most 

important risk factor for HCC in humans. It is estimated that 80% of 

HCC worldwide is etiologically associated with HBV. In the United 

States, although the infection rate in the general population is low, HBV 

is estimated to account for one-fourth of HCC cases among non-Asians 

[5].

In Egypt, the prevalence of HBV has not been adequately studied 

because of the attention paid to the increasing prevalence of HCV. 

Nonetheless, it could be assumed that what applies to HCV also 

applies to HBV – that is, that there has been a parallel increase in the 

incidence of HBV.

Hepatitis C virus. Chronic infection by HCV is an important risk factor 

for HCC in low-incidence countries like the United States. However, this 

virus is believed to play a relatively minor role in the development of 

HCC in Africa and Asia. In general, HCC develops only after 2 or more 
52 MECC Monograph 

Liver and Intrahepatic Bile Duct Cancer Chapter 5

Table 5.1. Liver and Intrahepatic Bile Duct Cancer: Age-Standardized Incidence Rates* for the Highest, Median, and Lowest Country 

within Continent, by Sex − 1993-1997

Continent Male Female

Country Rate Country Rate

 Total World

Highest China, Qidong County 95.7 Thailand, Khon Kaen 35.4

Median Switzerland, Basel 5.5 France, Bas-Rhin 1.9

Lowest Algeria 0.9 India, Karunagappally 0.3

Africa

Highest The Gambia 48.9 The Gambia 17.6

Median Zimbabwe, Harare 27.9Zimbabwe, Harare 11.6

Kyadondo, Uganda 6.5

Lowest Algeria 0.9 Algeria 0.9

Asia

Highest China, Qidong County 95.7 Thailand, Khon Kaen 35.4

Median Japan, Miyagi Prefecture 17.1 Singapore, Chinese 5.1

Lowest Israel, Jews born in Israel 1.4 India, Karunagappally 0.3

Europe

Highest Italy, Parma Province 19.6 Italy, Parma Province 6.6

Median Austria, Tyrol 5.5 Austria, Tyrol 1.9

Lowest The Netherlands, Eindhoven 1.4 The Netherlands, Maastricht 0.6

North

 America

Highest United States, California, Los Angeles, Korean 20.7 United States, California, Los Angeles, Korean 10.4

Median United States, New Jersey 4.6 United States, Michigan, Detroit, White 1.6

Lowest Canada, Prince Edward Island 1.0 Canada, Newfoundland 0.8

Oceania

Highest United States, Hawaii, Hawaiian 10.0 United States, Hawaii, Chinese 4.8

Median New Zealand 3.8 United States, Hawaii, White 1.5

Lowest Australia, Tasmania 2.3 Australia, South 0.9

South

 America

Highest Costa Rica 5.4 Ecuador, Quito 3.5

Median Cuba, Villa Clara 3.5 United States, Puerto Rico 2.5

Lowest Brazil, Compinas 1.5 Brazil, Compinas 0.6

*Rates are per 100,000 and are age-standardized to the World Standard Million.

Source: Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in five continents, volume VIII. IARC Scientific Publication No. 155. Lyon (France): International Agency for Research on Cancer; 2002.

decades of HCV infection, and the increased risk is restricted largely to 

patients with cirrhosis or advanced fibrosis. 

Factors that predispose to HCC among HCV-infected persons 

include male sex, older age, HBV co-infection, heavy alcohol 

intake, and possibly diabetes and a transfusion-related source of 

HCV infection. Other viral factors apparently play a minor role. The 

likelihood of development of HCC among HCV-infected persons is 

estimated to be 1%-3% after 30 years. Once cirrhosis is established, 

however, HCC develops at an annual rate of 1% to 4% [6].

The population of Egypt has a heavy burden of liver disease, 

mostly due to chronic infection with HCV. Overall prevalence of 

antibody to HCV in the general population is around 15%-20%. 
 MECC Monograph 53

Liver and Intrahepatic Bile Duct Cancer Chapter 5

It was hypothesized that the risk factor for HCV transmission that 

specifically sets Egypt apart from other countries is a personal 

history of parenteral anti-schistosomal therapy (PAT). A review 

of the Egyptian PAT mass-treatment campaigns, discontinued 

only in the 1980s, shows a very high potential for transmission of 

bloodborne pathogens. A cohort-specific HCV prevalence was lower 

in children and young adults than in older cohorts. These lower 

prevalence rates coincided with the gradual and final replacement 

of PAT with oral anti-schistosomal drugs at different points in time. 

Egypt’s mass campaigns of PAT may represent the world’s largest 

iatrogenic transmission of bloodborne pathogens [7]. 

Aflatoxin B1. Aflatoxin B1 is the most potent liver cancer-forming 

chemical known. It is a product of the mold Aspergillus flavus, found 

in food that has been stored in a hot and humid environment. This 

mold is found in such foods as peanuts, rice, soybeans, corn, and 

wheat. Aflatoxin B1 has been implicated in the development of HCC in 

southern China and Sub-Saharan Africa. It is thought to cause cancer 

by producing mutations in the p53 gene. These mutations work by 

interfering with the gene’s important tumor-suppressing functions [8].

In Egypt, aflatoxin contamination of food products is rampant. 

Methods of grain storage are not controlled, and there is lack 

of awareness of the dangers of improper storage. A study was 

conducted in 2 districts in Upper Egypt to measure the presence of 

fungal population in silage. Aflatoxins showed the highest incidence 

rates of occurrence in 22.5% of all samples analyzed. Other 

mycotoxins were detected in all samples [9].

Alcohol. Alcohol intake has also been incriminated as a risk factor for 

HCC. There is compelling epidemiologic data, supported by animal 

experiments, confirming the increased risk of cancer associated with 

alcohol consumption. Cancer of the liver associated with alcohol usually 

occurs in the setting of cirrhosis [10].

Interactions among risk factors. Sylla et al. [8] expressed the 

importance of interactions between HBV infection and exposure to 

aflatoxins in the development of HCC. There is evidence from both 

epidemiological studies and animal models that the 2 factors can act 

synergistically to increase the risk of HCC. The cellular and molecular 

mechanism of the interaction is as yet undefined. However, one 

possible mechanism attested to by studies in HBV transgenic mice is 

that chronic liver injury alters the expression of specific carcinogenmetabolizing enzymes, thus modulating the binding of aflatoxin to DNA 

in hepatocytes [8]. 

Co-infection with HBV and HCV could be considered a potential 

HCC risk, higher than the risk attributed to infection with either type 

of virus alone. A multivariate analysis done by Benvegnu and Alberti

shows that the risk of HCC is significantly higher in HBV and HCV 

co-infected patients, compared with those with single HBV surface 

antigen or anti-HCV positivity. These results indicate different 

patterns of risk factors, morphogenesis, and incidence of HCC 

development in HBV- and HCV-associated cirrhosis, suggesting 

different mechanisms of carcinogenesis [11].

Alcohol may act as a co-carcinogen, and it has strong synergistic 

effects with other risk factors, including HBV, HCV, aflatoxin, 

vinyl chloride, obesity, and diabetes mellitus. Alcohol enhances 

the effects of environmental carcinogens directly; it also enhances 

them indirectly by contributing to nutritional deficiency and 

impairing immunological tumor surveillance. Acetylaldehyde, the 

main metabolite of alcohol, causes hepatocellular injury and is an 

important factor in causing increased oxidant stress, which damages 

DNA [10].

RESULTS

Statistics provided by MECC registries showed that the liver was

not a common site of cancer, except for Egypt (Table 5.2). Liver 

cancer’s relative frequency was below 2.0% in the other MECC 

registries and in the US SEER population. In Egypt, however, 

liver cancer accounted for 12.7% of male cancers, 3.4% of female 
54 MECC Monograph 

Liver and Intrahepatic Bile Duct Cancer Chapter 5

cancers, and 8.1% of both sexes together. Male predominance was 

marked in Egyptians, with a 3.8:1 male-to-female ratio. Next were 

Cypriots (3.1:1), Israeli Arabs (3.0:1), and Jordanians and Israeli 

Jews (1.6:1 and 1.4:1, respectively). In US SEER data, the male-tofemale ratio was 2.2:1. It is important to note that the sex ratios for 

the MECC registries other than Egypt are based on small numbers; 

therefore, they are subject to considerable uncertainty. 

Overall Incidence

According to Table 5.2, the ASRs reported from all MECC 

registries, except Egypt, did not exceed 3.0 for males or 1.6 for 

females (Israeli Jews). The rates of US SEER were 5.9 for males, 2.1 

for females, and 4.2 for both sexes together – rates that were higher 

than all MECC registries except Egypt. 

The ASR for Egypt was 20.6 for males, 5.2 for females, and 12.8 

for both sexes together. The rate for Egyptian males was 7 times the 

second-highest MECC rate (Israeli Jews) and more than 3 times the 

corresponding US SEER rate. For females, the rate for Egyptians 

was more than 3 times the highest MECC registry rate (Israeli Jews) 

and more than twice the US SEER rate (Table 5.2). 

A ranking of countries in the world according to their reported liver 

cancer ASR showed that Egypt occupied the 90th percentile. Its rate 

was exceeded only by countries in East and Southeast Asia and 3 

countries in Africa (Gambia, Mali, and Zimbabwe) [1].

Age

To avoid reporting rates calculated on small numbers of 

observations, age was grouped into 3 categories, and rates were 

calculated for these groups (Table 5.3). The table shows the 

relatively young age distribution of liver cancer patients in Arab 

populations, which is a reflection of the younger age distribution of 

these populations compared with Israeli Jews, Cypriots, and the US 

SEER population. 

Table 5.2. Liver and Intrahepatic Bile Duct Cancer: Proportions of Total Cancers, Male-to-Female Ratios, and AgeStandardized Incidence Rates, by Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001

Cyprus

 1998-2001

Israel (Jews)

 1996-2001 

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER*

 1999-2001

Percent relative to 

total cancers

Total 1.1% 0.9% 1.1% 8.1% 1.3% 1.2%

Male 1.7% 1.1% 1.5% 12.7% 1.6% 1.6%

Female 0.6% 0.7% 0.6% 3.4% 1.0% 0.8%

Male-to-female ratio 3.1:1 1.4:1 3.0:1 3.8:1 1.6:1 2.2:1

Age-standardized 

incidence rate† 

Total 1.7 2.2 1.6 12.8 1.6 4.2

Male 2.8 3.0 2.7 20.6 1.9 5.9

Female 0.8 1.6 0.6 5.2 1.3 2.1

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

†Rates are per 100,000 and are age-standardized to the World Standard Million.
 MECC Monograph 55

Liver and Intrahepatic Bile Duct Cancer Chapter 5

Liver cancer ASRs showed a progressive increase with age. Below 

the age of 50 years, the incidence was generally low. Egyptian 

males had the highest rate (3.4), which is 5 times the rates in the 

other MECC registries and 2.5 times the US SEER rate. In the 70 

years-and-older age group, the ASR for Egyptian males was 107.3 

– almost 4 times the rate for Israeli Jews and 2.5 times the US SEER 

rate. The same general pattern was observed for rates among females 

aged 70 and older, but at a much lower level. Again, Egypt had the 

highest rate for females in this age group (32.2), followed by Israeli 

Jews (15.7). The US SEER rate for females in this age group was 

19.5. 

Subsites

As shown in Table 5.4, cancer in the liver was much more frequent 

than in intrahepatic bile ducts. In the MECC countries, the highest 

frequencies of cancer in the liver were in Egyptians (97.9%), 

followed by Israeli Arabs (96.9%). The US SEER frequency was 

87.2%. The frequency of cancer in intrahepatic bile ducts in the 

MECC populations was highest in Cypriots (13.0%), followed 

by Jordanians (12.0%). The US SEER frequency was 12.8%. The 

significance of these differences awaits further examination. 

Across MECC countries, large differences were seen in the ASRs 

of cancer in the liver. Egypt had the highest rate for males (20.1), 

nearly 4 times the US SEER rate (5.8). For other MECC registries, 

Table 5.3. Liver and Intrahepatic Bile Duct Cancer: Total Cases, Median Age, Age Distribution, and Age-Standardized Incidence Rates, by 

Age and Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001*

Cyprus

 1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER†

 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 69 52 17 900 525 375 64 48 16 848 671 177 233 143 90 6,581 4,463 2,118

Median age 67.1 67.7 64.5 71.4 70.6 72.5 56.4 58.7 40.0 59.4 59.3 60.2 59.5 59.5 59.7 67.0 64.8 71.4

Age Groups (Distribution)‡ 

<50 y 11.6% 13.5% - 8.6% 9.7% 6.9% 39.1% 29.2% 68.8% 20.2% 19.4% 23.2% 25.8% 25.9% 25.6% 14.6% 16.2% 11.3%

50-69 y 36.2% 32.7% 47.1% 36.2% 37.7% 34.1% 45.3% 54.2% 18.8% 63.3% 65.1% 56.5% 53.6% 53.8% 53.3% 43.0% 46.9% 34.8%

70+ y 52.2% 53.8% 47.1% 55.2% 52.6% 58.9% 15.6% 16.7% - 16.5% 15.5% 20.3% 20.6% 20.3% 21.1% 42.4% 37.0% 53.9%

Age Groups (Rates)§

Total rate 1.7 2.8 0.8 2.2 3.0 1.6 1.6 2.7 0.6 12.8 20.6 5.2 1.6 1.9 1.3 4.2 6.4 2.4

<50 y 0.4 0.6 - 0.3 0.4 0.2 0.5 0.6 0.4 2.3 3.4 1.1 0.3 0.4 0.3 0.9 1.3 0.5

50-69 y 4.9 6.8 3.1 7.0 9.3 5.0 5.6 10.3 1.2 51.8 84.9 19.3 5.7 6.7 4.7 14.7 22.6 7.4

70+ y 16.3 29.3 6.2 21.0 28.2 15.7 7.7 13.8 - 67.3 107.3 32.2 10.2 12.9 7.8 29.5 44.0 19.5

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Percentages should sum over a column to 100% (with some rounding). However, where a percentage has been suppressed because it is based on only 1 or 2 cases, the remaining percentages will not sum to 100%.

§Rates are per 100,000 and are age-standardized to the World Standard Million.
56 MECC Monograph 

Liver and Intrahepatic Bile Duct Cancer Chapter 5

the rates ranged between 1.7 for Jordanians and 2.7 for Israeli 

Jews. Rates for females were much lower compared with males; 

nevertheless, the Egyptian rate was still the highest (5.2). Rates for 

females in other MECC registries varied between 0.6 (Israeli Arabs) 

and1.4 (Israeli Jews). The US SEER rate (2.0) was a little higher 

than that of Israeli Jews.

Despite the marked variation in incidence rates of cancer in the liver 

across MECC registries, the rates of cancer of intrahepatic bile ducts 

were similar and very low. The highest rates were those of Egyptians 

and US SEER (0.3 and 0.5, respectively).

Histology

As shown in Table 5.5, microscopic proof of diagnosis varied 

between registries, possibly a reflection of diagnostic practices 

in different MECC countries. The frequency of histological or 

cytological diagnosis was remarkably high in Jordanians (98.0%), 

followed by Cypriots (90.0%). Next were Israeli Arabs and Jews 

(72.6% and 60.8%, respectively). The frequency was lowest in Egypt 

(40.5%). In the US SEER population, histological or cytological 

diagnosis was available for 72.0% of cases.

The most frequent histological diagnosis for both sexes was 

carcinoma, representing 98.6% in Egyptians, 98.4% in Cypriots, 

Table 5.4. Liver and Intrahepatic Bile Duct Cancer: Distribution of Cases and Age-Standardized Incidence Rates,* by 

Subsite and Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001†

Cyprus

 1998-2001

Israel (Jews)

 1996-2001 

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER‡

 1999-2001

Distribution

Liver

Total 87.0% 89.0% 96.9% 97.9% 88.0% 87.2%

Male 84.6% 91.2% 97.9% 97.6% 92.3% 89.9%

Female 94.1% 85.9% 93.8% 98.9% 81.1% 81.4%

Intrahepatic bile 

ducts

Total 13.0% 11.0% - 2.1% 12.0% 12.8%

Male 15.4% 8.8% - 2.4% 7.7% 10.1%

Female - 14.1% - - 18.9% 18.6%

Rates*

Liver 

Total 1.5 2.0 1.5 12.5 1.4 3.8

Male 2.4 2.7 2.6 20.1 1.7 5.8

Female 0.8 1.4 0.6 5.2 1.0 2.0

 Intrahepatic bile 

ducts

Total 0.2 0.2 - 0.3 0.2 0.5

Male 0.4 0.2 - 0.5 0.1 0.6

Female - 0.2 - - 0.3 0.4

*Rates are per 100,000 and are age-standardized to the World Standard Million.

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
 MECC Monograph 57

Liver and Intrahepatic Bile Duct Cancer Chapter 5

The frequency of sarcoma was low (around 1%). Unspecified cancer 

was also infrequent; the only exception was Israeli Arabs (8.5% for 

both sexes), but again this is based on only unspecified cases.

In Egypt, the most frequent histological diagnosis was HCC 

(84.9%). In the US SEER population, the frequency of HCC was 

72.4%. In other MECC registries, HCC was also the most common 

diagnosis, with frequencies that were variable but less than in Egypt 

and US SEER. The frequency of HCC in Israeli Jews was 69.1%, 

followed by Israeli Arabs (55.3%), Cypriots (53.2%), and Jordanians 

(41.7%). 

92.5% in Jordanians, 92.1% in Israeli Jews, and 72.3% in Israeli 

Arabs. The frequency in US SEER data was 96.9%. Differences in 

frequency between the sexes were minimal. 

The frequency of hepatoblastoma was generally low in all registries 

except for Israeli Arabs – especially females (14.9% for both sexes, 

9.1% for males, and 28.6% for females), a point that needs further 

confirmation, as the data are based on only 7 total hepatoblastoma 

cases.

Table 5.5. Liver and Intrahepatic Bile Duct Cancer: Total Cases Microscopically Confirmed, and Proportions of Microscopic Confirmation and Histologic 

Type, by Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001*

Cyprus

 1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER†

 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases microscopically 

confirmed 62 49 13 508 312 196 47 33 14 345 284 61 228 140 88 4,727 3,241 1,486

Microscopically confirmed 90.0% 93.2% 81.3% 60.8% 63.3% 57.1% 72.6% 68.1% 86.7% 40.5% 42.1% 34.3% 98.0% 97.7% 98.6% 72.0% 72.7% 70.2%

Distribution of Microscopically Confirmed Cases

Histologic distribution‡ 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Carcinoma 98.4% 98.0% 100.0% 92.1% 93.3% 90.3% 72.3% 78.8% 57.1% 98.6% 99.3% 95.1% 92.5% 93.6% 90.9% 96.9% 97.7% 95.3%

 Hepatocellular carcinoma 53.2% 53.1% 53.8% 69.1% 75.6% 58.7% 55.3% 60.6% 42.9% 84.9% 85.9% 80.3% 41.7% 49.3% 29.5% 72.4% 78.0% 60.2%

 Cholangiocarcinoma 33.9% 34.7% 30.8% 16.1% 12.2% 22.4% 10.6% 12.1% - 6.4% 5.3% 11.5% 39.0% 32.1% 50.0% 17.4% 13.4% 26.2%

 Unspecified carcinoma 8.1% 6.1% - 3.5% 3.2% 4.1% - - - 6.1% 6.7% - 10.1% 11.4% 8.0% 2.8% 2.3% 3.7%

 Other specified carcinomas - - 0.0% 3.3% 2.2% 5.1% - - 0.0% 1.2% 1.4% 0.0% 1.8% - 3.4% 4.4% 3.9% 5.2%

Hepatoblastoma 0.0% 0.0% 0.0% 1.4% 1.6% - 14.9% 9.1% 28.6% 0.9% - - 3.5% 3.6% 3.4% 1.1% 0.8% 2.0%

Sarcoma - - 0.0% 1.8% - 3.6% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 1.3% - - 1.0% 0.9% 1.4%

 Haemangiosarcoma 0.0% 0.0% 0.0% 1.2% 1.0% 1.5% - - 0.0% - 0.0% - - - - 0.4% 0.4% 0.5%

 Other sarcomas - - 0.0% 1.8% - 3.6% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 1.3% - - 0.6% 0.5% 0.9%

Unspecified cancer 0.0% 0.0% 0.0% 3.5% 3.5% 3.6% 8.5% - - - - 0.0% 1.8% - - 0.8% 0.6% 1.1%

Other specified cancer 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.1% - 0.2%

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Percentages should sum over a column to 100% (with some rounding). Where a percentage has been suppressed because it is based on only 1 or 2 cases, the remaining percentages will not sum to 100%.
58 MECC Monograph 

Liver and Intrahepatic Bile Duct Cancer Chapter 5

Contrary to the low frequency of HCC in Jordan and Cyprus, the 

frequency of cholangiocarcinoma was higher in these countries than 

in the other registries, including US SEER (39.0% and 33.9% for 

Jordan and Cyprus, respectively). In US SEER series, the reported 

frequency was 17.4%, which was slightly higher than in Israeli Jews 

(16.1%), followed by Israeli Arabs (10.6%) and Egyptians (6.4%). 

The cause of carcinomas of the bile ducts remains speculative, and 

various genetic alterations are of potential importance [12]. 

The frequency of unspecified carcinoma was also highest in 

Jordanians (10.1%) and Cypriots (8.1%) (Table 5.5). It seems likely 

that most of these unspecified carcinomas are really HCCs, where 

the medical notes are not specific enough to identify HCC.

Table 5.6 displays incidence rates for the different histological types. 

These rates were lower than those presented for total cases because 

they include only those patients with microscopic confirmation. 

Due to the wide variation among the registries in the percentage of 

cases that are microscopically confirmed (Table 5.5), comparisons 

of these rates across registries can be misleading. However, the table 

does show that the ASR of patients with a microscopic proof of HCC 

in Egypt was as high as 4.3, confirming the large magnitude of the 

liver cancer problem in Egypt. 

SUMMARY AND CONCLUSIONS

The current results indicated a marked variation in incidence rates, 

with low incidence in all registries except Egypt. The ASR for 

Egyptians was 20.6 for males, 5.2 for females, and 12.8 for both 

sexes together. The Egyptian rates for males were 7 times the highest 

MECC rate, and more than 3 times the corresponding US SEER rate. 

For Egyptian females, the rate was more than 3 times the highest 

MECC rate and more than twice the US SEER rate. Compared with 

rates reported in Cancer Incidence in Five Continents, Egypt ranked 

next to East and Southeast Asian countries and 3 African countries. 

The ASRs increased with age in all MECC registries, and reached 

107.3 for males and 32.2 for females in Egypt in the 70+ age group.

Male predominance was evident, with male-to-female ratios between 

3.8:1 and 1.4:1. The US SEER ratio was intermediate (2.1:1). The 

age distribution at diagnosis of patients in Arab populations was 

younger than that of Cypriot, Israeli Jewish, and US SEER patients. 

This difference could be attributed to the relatively young age 

structure of Arab populations. 

Cancer in the liver was more frequent than in the intrahepatic bile 

ducts. Hepatocellular carcinoma was the most frequent histological 

diagnosis. The frequency of pathological confirmation of diagnosis 

varied between countries, possibly due to differences in diagnostic 

practice. This was reflected in the rates of microscopically 

confirmed cases. 

Risk factors for HCC include HBV, HCV, aflatoxins, and alcohol. 

Except for alcohol, these are assumed to play an important role 

in the high incidence of HCC in Egypt. HBV vaccination of 

children and high-risk groups must be the priority in reducing the 

incidence of HCC. Measures to reduce food spoilage by fungi and 

the associated dietary exposure to aflatoxins are a desirable public 

health goal [13]. 

Successful antiviral therapy of patients with HCV-related cirrhosis 

may reduce the future risk for HCC. Given the current prevalence of 

HCV infection among persons 30 to 50 years of age, the incidence 

and mortality rates of HCC are likely to rise over the next 10 to 20 

years. Future research should focus on improving understanding 

of the incidence and risk factors for HCC, causes of HCV-related 

carcinogenesis, means of early detection, and better treatment for 

HCC. 
 MECC Monograph 59

Liver and Intrahepatic Bile Duct Cancer Chapter 5

Table 5.6. Liver and Intrahepatic Bile Duct Cancer: Age-Standardized Incidence Rates,* by Histological Diagnosis and Sex, in Cyprus, Israel (Jews and 

Arabs), Egypt, Jordan, and US SEER − 1996-2001†

Cyprus

 1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER‡

 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total rates* 1.5 2.6 0.7 1.3 1.8 0.9 1.1 1.7 0.6 5.1 8.6 1.7 1.6 1.9 1.2 3.1 4.7 1.8

Carcinoma 1.5 2.5 0.7 1.2 1.7 0.8 0.9 1.4 0.4 5.0 8.5 1.6 1.5 1.8 1.1 3.0 4.6 1.6

 Hepatocellular carcinoma 0.8 1.4 0.3 0.9 1.4 0.5 0.7 1.1 0.3 4.3 7.4 1.3 0.7 1.0 0.4 2.3 3.7 1.0

 Cholangiocarcinoma 0.5 0.8 0.2 0.2 0.2 0.2 0.1 0.2 - 0.3 0.5 0.2 0.6 0.6 0.7 0.5 0.6 0.4

 Unspecified carcinoma 0.1 0.1 - 0.0 0.0 0.0 - - - 0.3 0.6 - 0.2 0.2 0.1 0.1 0.1 0.1

 Other specified carcinomas - - 0.0 0.0 0.0 0.0 - - 0.0 0.1 0.1 0.0 0.0 - 0.0 0.1 0.2 0.1

Hepatoblastoma 0.0 0.0 0.0 0.0 0.0 - 0.1 0.1 0.1 0.0 - - 0.0 0.0 0.0 0.1 0.1 0.1

Sarcoma - - 0.0 0.0 - 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 - - 0.0 0.0 0.0

 Haemangiosarcoma 0.0 0.0 0.0 0.0 0.0 0.0 - - 0.0 - 0.0 - - - - 0.0 0.0 0.0

 Other sarcomas - - 0.0 0.0 - 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 - - 0.0 0.0 0.0

Unspecified cancer 0.0 0.0 0.0 0.0 0.1 0.0 0.1 - - - - 0.0 0.0 - - 0.0 0.0 0.0

Other specified cancer 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 - 0.0

*Rates are per 100,000 and are age-standardized to the World Standard Million.

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

Source: Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in five continents, volume VIII. IARC Scientific Publication No. 155. Lyon (France): International Agency for Research on Cancer; 2002.
60 MECC Monograph 

Liver and Intrahepatic Bile Duct Cancer Chapter 5

Acknowledgment. The author acknowledges the help of Abdel Rahman 

N. Zekry, PhD, professor of molecular biology, National Cancer 

Institute, Cairo University, Egypt.

REFERENCES

[1] Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in 

five continents, volume VIII. IARC Scientific Publication No. 155. Lyon 

(France): International Agency for Research on Cancer; 2002.

[2] McGlynn KA, London WT. Epidemiology and natural history of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2005;19:3-23.

[3] El Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin 

Gastroenterol 2002;35:S72-S78.

[4] Stuver SO. Towards global control of liver cancer? Semin Cancer Biol 

1998;8:299-306.

[5] Yu MC, Yuan JM, Govindarajan S, Ross RK. Epidemiology of hepatocellular carcinoma. Can J Gastroenterol 2000;14:703-9.

[6] El Serag HB. Hepatocellular carcinoma and hepatitis C in the United 

States. Hepatology 2002;36:S74-S83.

[7] Frank C, Mohamed MK, Strickland GT, Lavanchy D, Arthur RR, Magder 

LS, et al. The role of parenteral antischistosomal therapy in the spread of 

hepatitis C virus in Egypt. Lancet 2000;355:887-91.

[8] Sylla A, Diallo MS, Castegnaro J, Wild CP. Interactions between hepatitis 

B virus infection and exposure to aflatoxins in the development of hepatocellular carcinoma: a molecular epidemiological approach. Mutat Res 

1999;428:187-96.

[9] El Shanawany AA, Mostafa ME, Barakat A. Fungal populations and 

mycotoxins in silage in Assiut and Sohag governorates in Egypt, with 

a special reference to characteristic Aspergilli toxins. Mycopathologia 

2005;159:281-9.

[10] Voigt MD. Alcohol in hepatocellular cancer. Clin Liver Dis 2005;9:151-

69.

[11] Benvegnu L, Alberti A. Patterns of hepatocellular carcinoma development 

in hepatitis B virus and hepatitis C virus related cirrhosis. Antiviral Res 

2001;52:199-207.

[12] Tannapfel A, Wettekind C. Gallbladder and bile duct carcinoma, biology 

and pathology. Internist (Berl) 2004;45:33-41.

[13] Wild CP, Hall AJ. Primary prevention of hepatocellular carcinoma in 

developing countries. Mutat Res 2000;462:381-93.
 MECC Monograph 61

Lung Cancer Chapter 6

SAMIR AL-KAYED, M. BASSAM QASEM

BACKGROUND

Worldwide, lung cancer is the most commonly diagnosed cancer and 

causes more deaths than any other cancer [1,2]. Its high mortality 

rate results from both a high incidence rate and a low survival rate, 

with only 14% of US lung cancer patients surviving 5 years after 

diagnosis [3]. Lung cancer is also the leading cause of cancer death 

in most countries [4-6].

International variations in the incidence of lung cancer are striking, 

with age-standardized incidence rates (ASRs) per 100,000 below 10 

in parts of Africa, China, and South America, and over 100 in some 

Black populations in the United States [2,5]. 

Throughout all age groups, incidence of lung cancer rises sharply 

with age [4]. This pattern is sometimes complicated by cohort 

effects related to changes in tobacco consumption [7-9].

Tobacco use is by far the most important risk factor in the 

development of lung cancer. In 1979, the US Surgeon General 

estimated that 90% of lung cancer deaths in males and 79% in 

females were due to cigarette smoking [4]. Smoking more than 20 

cigarettes a day has been shown to confer a risk of between 15- 

and 25-fold relative to nonsmokers [10-12]. Both the duration and 

intensity of cigarette smoking increases the risk, as does the tar 

content and the lack of a filter [13]. The risk decreases with time 

after smoking cessation, with long-term ex-smokers approaching but 

not reaching the risk of nonsmokers [14]. Other types of tobacco 

smoking, such as pipe, cigar, and water-pipe smoking, are also 

linked to lung cancer, although the relative risks are not as high 

as for cigarette smoking [4]. Exposure to other persons’ cigarette 

smoke (known as passive smoking or environmental tobacco 

smoke) is also related to an increased risk of lung cancer, although 

the relative risk is understandably much lower than in smokers. 

Worldwide, the incidence of lung cancer among males is much 

higher than among females, due primarily to the lower prevalence 

of smoking among females. The sex difference in cigarette 

consumption has diminished, and in many countries lung cancer 

rates continue to increase among females. 

Smoking is related to all the major types of lung cancer, 

including squamous cell carcinoma, small cell carcinoma, and 

adenocarcinoma. It used to be thought that adenocarcinoma was not 

caused by smoking, but in the United States, adenocarcinoma is now 

the most common type of lung cancer in smokers [15]. 

Several other risk factors for lung cancer have been identified. 

Occupational exposures that increase the risk of lung cancer 

include asbestos [16], which also causes an increase in the risk of 

mesothelioma, a cancer of the pleura [17]. Asbestos exposure and 

cigarette smoking act synergistically, together raising the risk of 

lung cancer multiplicatively [18].

Other occupational exposures related to lung cancer include 

arsenic [19], chromium [20], polycyclic aromatic hydrocarbons 

[21], and radon. The latter exposure was first discovered among 

underground miners in North America, Europe, and Asia [22], but 

is now the source of concern for the general population because 

many household basements show relatively high levels of radon. It is 

estimated that in the United States, indoor radon may be the second 

most important risk factor for lung cancer after cigarette smoking 

[23]. Lung cancer is also one of the major effects of exposure to 

high doses of ionizing radiation, such as in medical and atomic 

radiation. Various pollutants in urban air are implicated in lung 

cancer incidence rates worldwide [4].
62 MECC Monograph 

Lung Cancer Chapter 6

Epidemiological investigations have shown associations between 

consumption of fresh vegetables and fruits and a low risk of lung 

cancer [24]. Investigations have focused on carotenoid intake 

and serum carotenoid levels [4], both of which have also shown 

associations with low risk of lung cancer. However, several 

randomized trials of beta-carotene supplementation have yielded 

the unexpected result that among smokers, high doses of betacarotene can increase the risk of lung cancer [25,26]. The biological 

explanation is as yet unclear. 

There has been some evidence of lung cancer clustering in families, 

with suggestions that heritable factors may also play a part in lung 

cancer etiology [4]. Much effort has gone into discovering genetic 

susceptibility factors, and the P450 gene CYP2D6, which regulates 

debrisoquine metabolism, was at one time thought to be important, 

but later results have indicated that at most its effect is modest [27]. 

Reduced activity of glutathione S-transferase (GST) has also been 

linked to increased risk of lung cancer, and GSTM1 deficiency is 

associated with a moderately elevated relative risk [28]. 

RESULTS

Table 6.1 presents the total numbers and proportions by age group, 

incidence rates age-standardized to the world standard, and ageand sex-specific incidence rates for MECC populations and the US 

SEER population.

The total numbers of cases from each population were at least a few 

hundred, except for Cypriot, Egyptian, and Israeli Arab females. The 

proportions of cases over 70 years of age were around 50% in the 

US SEER and Israeli Jewish populations, 40% in Cypriots, and 20%-

30% in Egyptians, Jordanians, and Israeli Arabs. These differences 

are largely due to differences in the population age distribution 

(Table 6.1).

The overall ASRs were much lower in the MECC populations 

than in US SEER. The rates in Israel (Jews and Arabs) were 

approximately half that of US SEER. In Cyprus, Jordan, and Egypt, 

rates were between one-third and one-fifth of the US SEER rate 

(Table 6.1).

Among males, the lung cancer ASR in MECC populations was 

highest in Israeli Arabs, followed by Israeli Jews, Cypriots, 

Jordanians, and Egyptians. The rate among Israeli Arab males was 

34% higher than in Israeli Jewish males (Table 6.1).

Worldwide statistics [2] show that the lung cancer ASRs for males 

in other Middle Eastern populations, such as Algeria (17.1) and 

Kuwait (20.0), were close to that in Jordan (16.4), while the rate in 

other Western countries, such as Canada (59.0) and Ireland (42.3), 

were similar to that in the United States. 

The lung cancer incidence rates in females were lower than in 

males. All the MECC female populations displayed rates far lower 

than in the US SEER female population. Among the MECC female 

populations, the highest rate was in Israeli Jews, but this was only 

one-third the rate in US SEER. All of the other MECC populations 

had rates less than half that of Israeli Jews, with Jordanians and 

Egyptians having the lowest rates. It is notable that the rate among 

Israeli Arab females was not much higher than the rates among 

Jordanian and Egyptian females, a reflection of the similarities in 

cultures and habits related to smoking among females in these 3 

Arab populations. The female ASRs in Algerians (1.9) and Omanians 

(2.6) [4] were somewhat lower than in Jordanians (3.1), Egyptians 

(3.7), and Israeli Arabs (4.8), but Kuwaitis (5.3) had a slightly 

higher rate. 

Table 6.1 also presents the age- and sex-specific incidence rates in 

4 broad age groups. As expected, the rates increased with age, from 

the youngest age group (<50 years of age) to the oldest (age 70 years 

and older). One interesting aspect of the age-specific incidence rates 

is that the ratio of the MECC population rates to the US SEER rates 
 MECC Monograph 63

Lung Cancer Chapter 6

Table 6.1. Lung Cancer: Number of Cases, Age Distribution, and Age-Standardized Incidence Rates, by Age and Sex, in Cyprus, Israel (Jews 

and Arabs), Egypt, Jordan, and US SEER − 1996-2001*

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 514 423 91 7,402 4,892 2,510 706 611 95 496 370 126 1,336 1,128 208 63,559 34,973 28,586

Age Groups (Distribution)

<50 8.4% 6.9% 15.4% 7.6% 6.9% 8.9% 13.5% 11.6% 25.3% 19.6% 16.2% 29.4% 15.3% 13.8% 23.1% 5.7% 5.5% 5.9%

50-59 19.1% 19.1% 18.7% 13.8% 13.5% 14.3% 24.5% 26.5% 11.6% 22.2% 22.7% 20.6% 26.0% 26.5% 23.1% 14.7% 14.9% 14.4%

60-69 31.7% 32.2% 29.7% 29.6% 31.9% 25.1% 31.7% 32.9% 24.2% 36.5% 39.5% 27.8% 37.0% 37.6% 33.7% 26.8% 27.7% 25.8%

70+ 40.9% 41.8% 36.3% 49.1% 47.7% 51.7% 30.3% 29.0% 38.9% 21.8% 21.6% 22.2% 21.8% 22.1% 20.2% 52.8% 51.9% 54.0%

Age Groups (Rates)‡

Total rate 13.4 23.4 4.7 19.0 28.4 11.4 20.4 38.0 4.8 7.7 11.9 3.7 9.9 16.4 3.1 39.2 48.6 31.9

<50 1.7 2.3 1.1 2.3 2.8 1.8 2.3 3.6 1.0 1.3 1.6 1.0 1.4 2.1 0.6 3.1 3.3 2.9

50-59 32.0 53.4 11.1 40.4 55.1 27.0 49.7 92.9 6.3 17.7 26.6 8.4 23.7 39.2 6.9 75.1 86.2 64.5

60-69 75.0 132.2 24.2 105.0 165.5 55.1 109.8 213.2 21.0 42.9 70.9 16.1 59.5 95.7 18.1 223.3 271.1 181.1

70+ 97.4 187.6 27.0 155.1 239.9 93.6 159.9 297.2 49.7 52.3 83.1 25.2 61.6 110.7 17.1 359.3 479.9 277.6

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004. 

‡Rates are per 100,000 and are age-standardized to the World Standard Million.

decreased with age. For example, the ratios of the rates in male 

Israeli Jews to those in the male US SEER population were 0.85 for 

<50 years of age, 0.64 for 50-60 years of age, 0.61 for 60-70 years 

of age, and 0.50 for age 70 years and older. For male Israeli Arabs, 

the ratios were 1.09 for <50 years of age, 1.08 for 50-60 years of 

age, 0.79 for 60-70 years of age, and 0.62 for age 70 years and older. 

Such decreasing ratios are suggestive (but not conclusive) evidence 

of a cohort effect. It is possible that more recent generations in 

the Middle East have increasingly taken up cigarette smoking, 

which has caused the younger age groups to have lung cancer rates 

more like those seen in the US population. Unfortunately, there 

is little information about the history of smoking prevalence in 

the MECC populations, except for that in Israeli Jews. Figure 6.1 

shows smoking prevalence from 1965 to 2000 in Israeli Jewish

and US males, as well as the lung cancer ASRs in both populations 

from the mid-1970s onwards. It appears that in the latter part of 

the 1960s, approximately 30 years before the period covered by 

this monograph, the smoking prevalence in Israel was not very 

much lower than in the United States, and that by 1973, 25 years 

before the monograph’s period, the smoking prevalence in Israel 

had surpassed that in the United States. Thus, although Figure 6.1 

does indeed indicate that recent generations of males in Israel have 

smoked as much or more than their counterparts in the United States, 

the similarity of the smoking prevalence 25-30 years before this 

monograph’s timeframe raises the question why Israeli rates of lung 

cancer are not already much closer to those of the United States. 

While further analysis is required, including an examination of past 
64 MECC Monograph 

Lung Cancer Chapter 6

0

10

20

30

40

50

60

70

1965

1967

1969

1971

1973

1975

1977

1979

1981

1983

1985

1987

1989

1991

1993

1995

1997

1999

0

10

20

30

40

50

60

70

Figure 6.1. Lung Cancer:Age-Standardized Incidence Rates and Smoking Prevalence among Israeli and US 

White Males – 1965-2000

Per 100,000 % Smoking

US SEER*: Lung Cancer

US: Smoking

Israel: Lung Cancer

Israel: Smoking

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

Source: Reproduced with permission of Dr. Gad Rennert, who compiled the data from a variety of sources.
 MECC Monograph 65

Lung Cancer Chapter 6

age-specific smoking prevalence and age-specific lung cancer rates, 

it is possible that genetic factors may explain some of the current 

differences between Israeli and US SEER rates. 

The histological type of lung cancer is an important factor in the 

epidemiology, treatment, and prognosis of lung cancers. Table 

6.2 shows data on the histology of lung and pleural cancers in the 

MECC and US SEER populations. 

The percentage of microscopically confirmed cases varied widely 

among the registries, with a very high rate in Jordan (97.2%), a rate 

of around 90% in Cyprus and US SEER registries, and lower rates in 

Israel and Egypt. The high rate in Jordan indicates possible underdiagnosis of lung cancer in that country, whereas the low rates in 

Israel indicate that the registry may sometimes be missing details of 

diagnosis in the information provided by the hospitals. The low rate 

in Egypt may arise from patterns of care of the elderly population 

there. 

Table 6.2 also indicates a remarkably high proportion of 

adenocarcinoma in the Cyprus population (54.4%), and a similarly 

remarkable proportion of large cell carcinoma in Egypt (25.6%). 

These findings, if confirmed, may provide new clues to the etiology 

of lung cancer. 

Table 6.2. Lung Cancer: Number of Cases and Proportions of Microscopic Confirmation and Histologic Type, by Sex, in Cyprus, Israel (Jews and Arabs), 

Egypt, Jordan, and US SEER − 1996-2001*

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases microscopically 

confirmed 467 381 86 5,936 3,950 1,986 594 523 71 383 288 95 1,298 1,095 203 57,126 31,672 25,454

Microscopically confirmed 90.9% 90.1% 94.5% 80.2% 80.7% 79.1% 84.1% 85.6% 74.7% 77.2% 77.8% 75.4% 97.2% 97.1% 97.6% 89.9% 90.6% 89.0%

Distribution of Microscopically Confirmed Cases

Histologic distribution‡ 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Carcinoma 95.3% 94.8% 97.7% 96.3% 96.4% 96.1% 95.0% 95.2% 93.0% 94.8% 94.4% 95.8% 96.7% 96.9% 95.6% 98.8% 98.8% 98.8%

 Squamous cell carcinoma 24.6% 27.0% 14.0% 24.8% 29.7% 15.0% 29.0% 31.4% 11.3% 21.1% 25.3% 8.4% 31.4% 33.9% 17.7% 21.0% 24.8% 16.3%

 Adenocarcinoma 54.4% 49.1% 77.9% 36.6% 30.9% 47.8% 31.0% 28.5% 49.3% 29.5% 23.3% 48.4% 27.7% 24.7% 43.4% 37.2% 34.2% 40.9%

 Small cell carcinoma 8.1% 9.4% - 9.6% 10.8% 7.3% 14.8% 14.3% 18.3% 13.3% 15.3% 7.4% 13.4% 14.3% 8.4% 14.1% 13.1% 15.3%

 Large cell carcinoma 2.1% 2.4% - 3.9% 4.3% 3.1% 3.2% 3.6% 0.0% 25.6% 26.4% 23.2% 3.5% 3.5% 3.9% 6.2% 6.4% 5.9%

 Other specified carcinomas 3.4% 3.7% - 16.9% 16.0% 18.7% 13.0% 12.8% 14.1% 2.4% 2.8% - 4.9% 4.6% 6.9% 8.3% 8.1% 8.6%

 Unspecified carcinoma 2.6% 3.2% 0.0% 4.5% 4.7% 4.2% 4.0% 4.6% 0.0% 2.9% 1.4% 7.4% 15.8% 15.9% 15.3% 12.1% 12.3% 11.8%

Sarcoma - - 0.0% 0.5% 0.5% 0.6% - 0.0% - 0.0% 0.0% 0% 0.4% 0.0% 2.5% 0.2% 0.2% 0.2%

Mesothelioma - - 0.0% 0.3% 0.4% 0.2% - - 0.0% - - 0.0% 0.3% 0.4% 0.0% 0.1% 0.1% 0.0%

Unspecified cancer 4.1% 4.5% - 2.5% 2.4% 2.8% 3.7% 4.0% - 5.0% 5.2% 4.2% 2.3% 2.5% 1.5% 0.8% 0.8% 0.8%

Other specified types 0.0% 0.0% 0.0% 0.3% 0.3% 0.4% 0.7% - - 0.0% 0.0% 0.0% 0.3% 0.3% - 0.2% 0.2% 0.2%

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Percentages should sum over a column to 100% (with some rounding). However, where a percentage has been suppressed because it is based on only 1 or 2 cases, the remaining percentages will not sum to 100%.
66 MECC Monograph 

Lung Cancer Chapter 6

SUMMARY AND CONCLUSIONS

The data show that lung cancer incidence in the MECC populations 

was much lower than in the US SEER population. However, the 

younger age groups (under 60 years of age) in the Israeli Arab male 

population had rates comparable to those in US SEER, and it is 

possible that a cohort effect is in progress, whereby rates in the older 

age groups will also reach or surpass those in the United States. 

There is also a hint of a similar phenomenon among the Israeli 

Jewish male population, although from past smoking prevalence 

data one might expect to see higher rates than are currently being 

observed. It is possible that genetic factors may explain part of 

the difference currently seen between Israeli Jewish and US SEER 

rates. Apart from the Israeli Arabs, other Arab populations in MECC 

appear to have had low rates, although reports of higher smoking 

prevalence in these populations give reason for greater vigilance. 

Unusual histological patterns in Cyprus, with a high proportion of 

adenocarcinoma, and in Egypt, with a high proportion of large cell 

carcinoma, deserve further examination. 

REFERENCES

[1] Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence. Mortality and prevalence worldwide. IARC cancer base no. 5, 

version 2.0. Lyon (France): IARC Press; 2004.

[2] Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in 

five continents, volume VIII. IARC Scientific Publication No. 155. Lyon 

(France): International Agency for Research on Cancer; 2002.

[3] Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, et al. 

SEER cancer statistics review, 1975-2002. 2003. Available at: http://seer.

cancer.gov/csr/1975_2000/. [Last Accessed: 12/05].

[4] Blot WJ, Fraumeni JF, Jr. Cancers of the lung and pleura. In: Schottenfeld 

D, Fraumeni JF, Jr., editors. Cancer epidemiology and prevention, second 

edition. New York (NY): Oxford University Press; 1996. p. 637-65.

[5] Devesa SS, Bray F, Vizcaino AP, Parkin DM. International lung cancer 

trends by histologic type: male:female differences diminishing and adenocarcinoma rates rising. Int J Cancer 2005;117:294-9.

[6] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA 

Cancer J Clin 2005;55:74-108.

[7] Thun MJ, Henley SJ, Calle EE. Tobacco use and cancer: an epidemiologic 

perspective for geneticists. Oncogene 2002;21:7307-25.

[8] Jemal A, Chu KC, Tarone RE. Recent trends in lung cancer mortality in 

the United States. J Natl Cancer Inst 2001;93:277-83.

[9] Jemal A, Ward E, Thun MJ. Contemporary lung cancer trends among U.S. 

women. Cancer Epidemiol Biomarkers Prev 2005;14:582-5.

[10] Hammond EC. Smoking in relation to the death rates of one million men 

and women. Natl Cancer Inst Monogr 1966;19:127-204.

[11] Doll R, Peto R, Wheatley K, Gray R, Sutherland I. Mortality in relation 

to smoking: 40 years’ observation on male British doctors. Br Med J 

1994;309:901-11.

[12] McLaughlin JK, Hrubec Z, Blot WJ, Fraumeni JF, Jr. Smoking and 

cancer mortality among U.S. veterans: a 26-year follow-up. Int J Cancer 

1995;60:190-3.

[13] Lubin JH, Blot WJ, Berrino F, Flamant R, Gillis CR, Kunze M, et al. 

Patterns of lung cancer risk according to type of cigarette smoked. Int J 

Cancer 1984;33:569-76.

[14] International Agency for Research on Cancer. Tobacco smoking: monographs on the evaluation of carcinogenic risk of chemicals to man, volume 

38. Lyon (France): International Agency for Research on Cancer; 1986.

[15] U.S. Surgeon General and Centers for Disease Control and Prevention. 

The health consequences of smoking. A report of the Surgeon General. 

7-12-2005. Available at: http://www.cdc.gov/tobacco/sgr/sgr_2004/index.

htm. [Last Accessed: 1/06].

[16] McDonald JC, McDonald AD. Epidemiology of asbestos-related lung 

cancer. In: Antman K, Aisner J, editors. Asbestos related malignancy. 

Orlando (FL): Grune and Stratton; 1987. p. 57-9.

[17] McDonald AD, McDonald JC. Epidemiology of malignant mesothelioma. 

In: Antman K, Aisner J, editors. Asbestos related malignancy. Orlando 

(FL): Grune and Stratton; 1987. p. 31-55.

[18] Berry G, Newhouse ML, Antonis P. Combined effect of asbestos and 

smoking on mortality from lung cancer and mesothelioma in factory 

workers. Br J Ind Med 1985;42:12-8.
 MECC Monograph 67

Lung Cancer Chapter 6

[19] Blot WJ, Fraumeni JF, Jr. Arsenic and lung cancer. In: Samet J, editor. The 

epidemiology of lung cancer. New York (NY): Marcell Dekker; 1994. p. 

207-18.

[20] Alderson MR, Rattan NS, Bidstrup L. Health of workmen in the chromate-producing industry in Britain. Br J Ind Med 1981;38:117-24.

[21] International Agency for Research on Cancer. Polynuclear aromatic 

hydrocarbons: monographs on the evaluation of carcinogenic risk of 

chemicals to man, parts I-IV, volumes 32-35. Lyon (France): International 

Agency for Research on Cancer; 1985.

[22] Samet JM. Radon and lung cancer. J Natl Cancer Inst 1989;81:745-57.

[23] Lubin JH, Boice JD, Jr. Estimating Rn-induced lung cancer in the United 

States. Health Phys 1989;57:417-27.

[24] Colditz GA, Stampfer MJ, Willett WC. Diet and lung cancer. A review of 

the epidemiologic evidence in humans. Arch Intern Med 1987;147:157-

60.

[25] The Alpha-Tocopherol, Beta Carotene (ATBC) Cancer Prevention 

Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 

1994;330:1029-35.

[26] Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass 

A, et al. Effects of a combination of beta carotene and vitamin A on lung 

cancer and cardiovascular disease. N Engl J Med 1996;334:1150-5.

[27] Shaw GL, Falk RT, Deslauriers J, Frame JN, Nesbitt JC, Pass HI, et al. 

Debrisoquine metabolism and lung cancer risk. Cancer Epidemiol Biomarkers Prev 1995;4:41-8.

[28] McWilliams JE, Sanderson BJ, Harris EL, Richert-Boe KE, Henner WD. 

Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk. 

Cancer Epidemiol Biomarkers Prev 1995;4:589-94.
68 MECC Monograph 
 MECC Monograph 69

Laryngeal Cancer Chapter 7

SAMIR AL-KAYED, M. BASSAM QASEM

BACKGROUND

Cancer of the larynx may develop in the glottis (the central part 

of the larynx that includes the vocal cords), the supra glottis (the 

area above the glottis), or more rarely in the sub glottis (the area of 

connection of the larynx to the trachea). It is much more commonly 

diagnosed in males than females and in developed countries among 

those aged 60 years and older. 

Incidence of laryngeal cancer among males is high in some parts 

of South America (Argentina, Uruguay, and Cuba), in southwestern 

Europe (Italy, Spain, and France), in parts of Central/Eastern Europe 

(Croatia, Slovakia, Yugoslavia, Poland, and Belarus) and in US 

Blacks. In all these populations, the age-standardized incidence rate 

(ASR) per 100,000 in males is above 10 per annum. Among females, 

the highest rates are in US Blacks, but these rates do not exceed 3 

[1]. 

The primary risk factors for laryngeal cancer are tobacco and 

alcohol. A careful review of several sources of epidemiological 

evidence concluded that there is a strong dose-response relationship 

between cigarette smoking and laryngeal cancer [2]. Estimates of 

relative risk for those reporting smoking over 20 cigarettes per day 

range from around 4 [3] to 30 [4]. Studies have also shown that the 

risk decreases with the numbers of years since smoking cessation 

[5,6]. 

The evidence that alcohol exposure causes laryngeal cancer is 

strong, although its quantification is more difficult to pinpoint 

because researchers have used different measures for exposure. Most 

investigators have identified a four- to five-fold risk between heavy 

drinkers and nondrinkers, although the definition of a heavy drinker 

has varied [7-11]. 

Many studies have shown that alcohol consumption and cigarette 

smoking have an independent multiplicative effect on risk. The 

most recent reports are those of Dosemeci et al. [11], carried out in 

Turkey, and Schlecht et al. [12], in Brazil. This means that a heavy 

smoker who also drinks heavily may have a risk 60 times that of 

someone who abstains from smoking and alcohol (fifteen-fold due 

to the smoking, multiplied by four-fold due to the alcohol). There 

are also some reports of synergism – in other words, higher relative 

risks for smoking among drinkers than among nondrinkers [10,13], 

but this has not been seen in other studies [14-16]. 

The fact that these risk behaviors are more common among males 

than females probably explains the approximately five-fold 

difference in the incidence of laryngeal cancer between men and 

women seen in many countries. 

Poor eating habits are often associated with alcohol abuse and may 

be part of the reason that the incidence of laryngeal cancer is higher 

among heavy drinkers. In particular, low carotenoid intake, resulting 

from low consumption of fresh vegetables, has been associated with 

a greater risk of laryngeal cancer [17]. In a Phase II prevention trial, 

13-cis retinoic acid was found to reduce the risk of second primary 

head and neck tumors [18]. 

Occupational exposure studies have suggested links between 

laryngeal cancer and exposure to asbestos or chromium [19]; 

however, these suggested relationships have not been confirmed. 
70 MECC Monograph 

Laryngeal Cancer Chapter 7

RESULTS

Table 7.1 presents the numbers, proportions by age group, incidence 

rates age-standardized to the world standard, and age-specific 

incidence rates for MECC populations and the US SEER population.

The total numbers of cases from each population were less than 150, 

except for Israeli Jews, Jordanians, and the US SEER population; 

therefore, extensive analysis was not possible. Numbers among 

females were particularly low, except in Israeli Jews and US SEER. 

The proportion of cases in persons over 60 years of age was around 

two thirds in US SEER, Israeli Jews, and Cypriots, and around one 

half in Egyptians, Jordanians, and Israeli Arabs. These differences 

are largely due to differences in the population age distribution. 

Unlike lung cancer, the overall ASRs for laryngeal cancer were 

not much lower in the MECC populations than in the US SEER 

population. The rate in Israeli Arab males (6.0) appeared to exceed 

that in US SEER males (4.6). The rate in Israeli Jews, Jordanians, 

and Egyptians was similar to the SEER rate. The rate in Cypriots 

appeared lower than in the other MECC populations. The laryngeal 

cancer rates among females in MECC populations appeared to 

be very low, but estimates are based on such small numbers that 

the actual levels cannot be precisely determined. The exception 

is among Israeli Jewish females, who appeared to have a lower 

incidence rate (0.6) than that of US SEER females (1.0). 

The MECC rates of laryngeal cancer in males appeared similar to 

that of Algeria (4.3), but higher than those reported in Kuwait (2.9) 

and Oman (1.6). The low MECC rates in females are similar to those 

in other Middle Eastern countries [1].

Given that cigarette smoking is the major risk factor for both 

laryngeal cancer and lung cancer, the different patterns seen in the 

incidence rates are puzzling. One might expect the ratios of the 

ASRs between 2 countries to be similar, but as mentioned above, 

laryngeal cancer incidence in MECC populations is similar to that 

of SEER, whereas lung cancer incidence rates in MECC are much 

lower than in SEER. This difference cannot be explained by alcohol 

consumption. Levels of alcohol consumption are higher in the SEER 

Table 7.1. Laryngeal Cancer: Number of Cases, Age Distribution, and Age-Standardized Incidence Rates, by Age and Sex, in Cyprus, Israel (Jews and 

Arabs), Egypt, Jordan, and US SEER − 1996-2001*

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 59 53 6 886 756 130 112 103 9 145 133 12 365 335 30 3,927 3,107 820

Age Groups (Distribution)

<60 y 28.8% 30.2% - 30.5% 30.6% 30.0% 49.1% 50.5% 33.3% 51.7% 50.4% 66.7% 46.6% 46.0% 53.3% 33.2% 32.9% 34.4%

60+ y 71.2% 69.8% 83.3% 69.5% 69.4% 70.0% 50.9% 49.5% 66.7% 48.3% 49.6% 33.3% 53.4% 54.0% 46.7% 66.8% 67.1% 65.6%

Age Groups (Rates)‡

Total rate 1.6 3.0 0.2 2.4 4.6 0.6 3.1 6.0 0.5 2.2 4.2 0.3 2.7 4.8 0.4 2.7 4.6 1.0

<60 y 0.6 1.1 - 1.0 1.9 0.3 1.5 2.7 0.2 1.1 2.0 0.2 1.2 2.0 0.2 1.0 1.7 0.4

60+ y 9.5 18.7 1.6 13.7 26.9 3.4 16.5 32.0 3.3 11.3 22.2 1.3 15.1 27.4 2.2 15.8 28.3 5.8

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Rates are per 100,000 and are age-standardized to the World Standard Million.
 MECC Monograph 71

Laryngeal Cancer Chapter 7

populations than in MECC, so one might expect an even larger 

difference between MECC and SEER in laryngeal cancer incidence 

than in lung cancer incidence – the opposite of the pattern observed. 

Table 7.2 shows a comparison of the percentage of lung cancer cases 

and laryngeal cancer cases by age among males in the US SEER 

population. This shows that laryngeal cancer tends to develop at an 

earlier age than lung cancer. Other data show the same trend. One 

may therefore infer that the latent period to laryngeal cancer after 

smoking begins is shorter than for lung cancer. This being the case, 

the similarity of laryngeal cancer rates in MECC and SEER could be 

hypothesized to be due to the similarity in more recent years of the 

smoking prevalence in these populations (for example, see Figure 

6.1). Conversely, lung cancer rates could be hypothesized to be 

different due to higher smoking prevalence in the SEER population 

in a period previous to that shown in Figure 6.1. 

However, this hypothesis does not seem to hold on examination 

of the age-specific rates of laryngeal cancer in Israeli Jewish and 

US SEER males, by 5-year age groups (Table 7.3). If the above 

hypothesis were true, one would expect to see Israeli rates somewhat 

higher at younger ages and somewhat lower at older ages. Instead, 

one sees that rates are similar at all ages. 

The great majority of registered cases of laryngeal cancers are 

microscopically confirmed. In the US SEER population, Cyprus, and 

Jordan, the percentage is over 98%. In Egypt and Israel, it is around 

90% (see Table 1.2). Differences in microscopic confirmation rates 

between the registries are discussed in Chapter 1. 

SUMMARY AND CONCLUSIONS

The incidence of laryngeal cancer in males in the MECC populations 

was comparable to that in US SEER, except that it appeared 

somewhat higher in Israeli Arabs and somewhat lower in Cypriots. 

One might expect that the MECC rates should be lower than in the 

US SEER population, similar to lung cancer, but this was not the 

case. Further investigation of the reasons seems indicated. 

Table 7.2. Laryngeal and Lung Cancer: Age Distribution of Cases among US SEER* Males --1999-2001†

Laryngeal Cancer

1999-2001

Lung Cancer 

1999-2001

Total cases 3,107 34,973

<35 y 0.2% 0.2%

35-39 y 0.7% 0.5%

40-44 y 2.7% 1.6%

45-49 y 5.7% 3.1%

50-54 y 10.5% 5.9%

55-59 y 12.9% 9.0%

60-64 y 15.2% 12.6%

65-69 y 15.7% 15.1%

70-74 y 15.1% 18.5%

75+ y 21.1% 33.4%

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

†”[Numeral]” (italic) = 0 or 3-15 cases.

Table 7.3. Laryngeal and Lung Cancer: Age-Standardized and AgeSpecific Incidence Rates* among Israeli Jewish and US SEER Males − 

1996-2001

Laryngeal Cancer

Israel (Jews)

1996-2001

Laryngeal Cancer

US SEER†

1999-2001

Lung Cancer

Israel (Jews) 

1996-2001

Lung Cancer

US SEER†

1999-2001

Total rate 4.6 4.6 28.4 48.6

40-44 y 2.2 1.8 9.9 11.6

45-49 y 4.5 4.3 20.2 26.6

50-54 y 11.5 9.2 35.8 58.7

55-59 y 15.3 15.4 79.2 120.7

60-64 y 23.0 24.1 137.6 225.4

65-69 y 27.6 30.7 202.6 332.1

70-74 y 32.1 33.5 242.9 461.0

75+ y 28.5 27.8 236.8 498.9

*Rates are per 100,000 where appropriate, and are age-standardized to the World Standard Million.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
72 MECC Monograph 

Laryngeal Cancer Chapter 7

Since cigarette smoking is the major known risk factor for laryngeal 

cancer, and alcohol consumption in the MECC populations is 

generally low, monitoring of smoking prevalence combined with 

programs for smoking cessation would be expected to help reduce 

the incidence of laryngeal cancer in MECC countries. 

REFERENCES

[1] Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in 

five continents, volume VIII. IARC Scientific Publication No. 155. Lyon 

(France): International Agency for Research on Cancer; 2002.

[2] Rothman KJ, Cann CI, Flanders D, Fried MP. Epidemiology of laryngeal 

cancer. Epidemiol Rev 1980;2:195-209.

[3] Maier H, Tisch M. Epidemiology of laryngeal cancer: results of the Heidelberg case-control study. Acta Otolaryngol Suppl 1997;527:160-4.

[4] Maier H, Dietz A, Gewelke U, Heller WD, Weidauer H. Tobacco and 

alcohol and the risk of head and neck cancer. Clin Investig 1992;70:320-7.

[5] Franceschi S, Talamini R, Barra S, Baron AE, Negri E, Bidoli E, et al. 

Smoking and drinking in relation to cancers of the oral cavity, pharynx, 

larynx, and esophagus in northern Italy. Cancer Res 1990;50:6502-7.

[6] Schlecht NF, Franco EL, Pintos J, Kowalski LP. Effect of smoking cessation and tobacco type on the risk of cancers of the upper aero-digestive 

tract in Brazil. Epidemiology 1999;10:412-8.

[7] Herity B, Moriarty M, Daly L, Dunn J, Bourke GJ. The role of tobacco 

and alcohol in the aetiology of lung and larynx cancer. Br J Cancer 

1982;46:961-4.

[8] Brownson RC, Chang JC. Exposure to alcohol and tobacco and the risk of 

laryngeal cancer. Arch Environ Health 1987;42:192-6.

[9] Tuyns AJ, Esteve J, Raymond L, Berrino F, Benhamou E, Blanchet F, 

et al. Cancer of the larynx/hypopharynx, tobacco and alcohol: IARC 

international case-control study in Turin and Varese (Italy), Zaragoza and 

Navarra (Spain), Geneva (Switzerland) and Calvados (France). Int J Cancer 1988;41:483-91.

[10] Choi SY, Kahyo H. Effect of cigarette smoking and alcohol consumption 

in the aetiology of cancer of the oral cavity, pharynx and larynx. Int J 

Epidemiol 1991;20:878-85.

[11] Dosemeci M, Gokmen I, Unsal M, Hayes RB, Blair A. Tobacco, alcohol 

use, and risks of laryngeal and lung cancer by subsite and histologic type 

in Turkey. Cancer Causes Control 1997;8:729-37.

[12] Schlecht NF, Franco EL, Pintos J, Negassa A, Kowalski LP, Oliveira BV, 

et al. Interaction between tobacco and alcohol consumption and the risk 

of cancers of the upper aero-digestive tract in Brazil. Am J Epidemiol 

1999;150:1129-37.

[13] Wynder EL, Covey LS, Mabuchi K, Mushinski M. Environmental factors 

in cancer of the larynx: a second look. Cancer 1976;38:1591-601.

[14] Baron AE, Franceschi S, Barra S, Talamini R, La Vecchia C. A comparison of the joint effects of alcohol and smoking on the risk of cancer across 

sites in the upper aerodigestive tract. Cancer Epidemiol Biomarkers Prev 

1993;2:519-23.

[15] Zheng W, Blot WJ, Shu XO, Gao YT, Ji BT, Ziegler RG, et al. Diet and 

other risk factors for laryngeal cancer in Shanghai, China. Am J Epidemiol 1992;136:178-91.

[16] Falk RT, Pickle LW, Brown LM, Mason TJ, Buffler PA, Fraumeni JF, Jr. 

Effect of smoking and alcohol consumption on laryngeal cancer risk in 

coastal Texas. Cancer Res 1989;49:4024-9.

[17] McLaughlin JK, Gridley G, Block G, Winn DM, Preston-Martin S, 

Schoenberg JB, et al. Dietary factors in oral and pharyngeal cancer. J Natl 

Cancer Inst 1988;80:1237-43.

[18] Hong WK, Lippman SM, Itri LM, Karp DD, Lee JS, Byers RM, et al. 

Prevention of second primary tumors with isotretinoin in squamous-cell 

carcinoma of the head and neck. N Engl J Med 1990;323:795-801.

[19] Austin DF, Reynolds P. Laryngeal cancer. Cancer epidemiology and prevention, second edition. New York (NY): Oxford University Press; 1996.
 MECC Monograph 73

Breast Cancer Chapter 8

GAD RENNERT

BACKGROUND

Breast cancer is the most common cancer in women in developed 

Western countries [1] and is becoming ever more significant in 

many developing countries [2]. Although incidence rates are 

increasing, mortality rates are stable, representing an improved 

survival rate. This improvement can be attributed to effective means 

of early detection, mainly mammography, as well as to significant 

improvement in treatment options.

RISK FACTORS

Breast cancer should be largely viewed as a disease predominantly 

influenced by risk factors related to lifestyle, as only approximately 

15% of all breast cancer cases can be attributed to familial and 

genetic influences [3]. Most known risk factors for breast cancer can 

be linked to hazardous effects of hormonal exposures [4], although 

other risk factors such as exposure to ionizing radiation are also 

relevant in some populations [5,6]. 

Reproduction-Related Exposures 

Early age at menarche, late age at menopause [4], small number 

of children and nulliparity, late age at first birth [7], and little or 

no breastfeeding [8,9] have all been associated with an increased 

risk of developing breast cancer. Although several retrospective 

studies have suggested that induced abortion is related to an 

increased risk of this disease, this is not seen in prospective studies 

[10], and its status as a breast cancer risk factor is unclear. The 

period of exposure to sex hormones before the first full-term 

pregnancy is a time when the breast tissue is especially susceptible 

to carcinogenesis. Long-term use of hormone replacement therapy, 

but apparently not long-term use of oral contraceptives, is also 

related to increased risk of breast cancer [11-14]. Despite the use of 

mega-doses of hormones in fertility treatments, there is no current 

evidence that these treatments are hazardous to the breast [15,16]. 

Of major interest are risk factors for which there is a potential to 

reduce risk at the population level. Use of external hormones and 

breastfeeding probably are the 2 best candidates. Recent metaanalyses have demonstrated that long-term breastfeeding can be 

linked with up to a 30% reduction in breast cancer risk. 

Benign Breast Disease

History of benign breast disease is also related to increased risk of 

breast cancer [17]. The risk, however, is mostly restricted to women 

who underwent biopsies, and especially those in whom atypical 

hyperplasia was found in such biopsies [18].

Nutritional Factors

The role of diet and nutrition in the etiology of breast cancer has 

been under debate for decades. Dietary fat has been the most 

investigated food constituent studied in this regard. It is currently 

believed that a high-fat diet is not directly related to the risk 

of breast cancer [19,20]. Overall caloric intake, and obesity in 

particular with certain weight-gain patterns, are related to increased 

breast cancer risk, with different effects between pre- and postmenopausal women [21,22]. This is also in line with a proven role 

of regular physical activity in reducing breast cancer risk [23]. High 

fruit and vegetable consumption is related to decreased breast cancer 

risk in most, but not all, studies [24]. Specifically, the consumption 

of cruciferous vegetables has been shown in vitro and in vivo to be 

related to such protection [25]. Of all food items studied, regular 

alcohol consumption, even at moderate levels, has consistently been 
74 MECC Monograph 

Breast Cancer Chapter 8

found to be related to a mild increase in breast cancer risk in women 

[26,27]. 

Other Lifestyle and Environmental Risk Factors 

Active and passive smoking have recently been shown to be related 

to breast cancer risk [27,28]. Ionizing radiation has been shown 

to increase the risk of breast cancer in studies following cohorts 

exposed to the A-bomb as well as in studies of women exposed to 

medical radiation [5,6]. 

Numerous studies have failed to show that environmental hazards, 

such as exposure to specific pollutants, are substantially related 

to breast cancer risk. Some have suggested that exposure to 

polychlorinated biphenyls (known as PCBs) and organochlorines 

carries increased risk of breast cancer, but these suggestions have 

not been substantiated in well-designed studies [29-31].

High Breast Density 

High breast density, as reflected on mammography films, has been 

shown to be one of the most significant markers of breast cancer risk 

[32]. Dense breast tissue probably reflects high hormonal exposure 

and is typical of young women, women using hormone replacement 

therapy, and those who are BRCA gene carriers.

Genetic Factors 

An established proportion of all breast cancer cases is caused by 

mutations in specific genes, mainly the BRCA genes. This proportion 

differs between different ethnic groups, and is especially high among 

Jewish women of Ashkenazi and Iraqi origin [33-38]. In the latter 

group, up to 10% of all newly diagnosed breast cancers are due to 

mutations in these genes. In addition to BRCA gene mutations, other 

genes such as AT and p53 are also involved in the development of 

breast cancer [3]. A variety of single nucleotide polymorphisms 

in genes encoding phase I and phase II enzymes, as well as other 

enzymes involved in the hormonal metabolism, are thought to 

interact with hormonal, nutritional, and radiological exposures to 

increase the risk of breast cancer. 

Risk Factor Summary

Differences in prevalence of exposure to these lifestyle and genetic 

risk factors among women from different countries in the Middle 

East are probably responsible for the variability in breast cancer 

incidence seen between countries in this area [39,40]. Time 

trends in the prevalence of the lifestyle risk factors can be directly 

correlated with time trends in breast cancer incidence. Delay in 

time of first pregnancy, decrease in number of children and in 

breastfeeding, increase in use of external hormones, and a move 

toward high-calorie Western diets are all responsible for the current 

trends in breast cancer incidence in the developed as well as the 

developing countries in the Middle East.

RESULTS 

Overall Incidence

Breast cancer was the leading tumor in females in all cancer 

registries involved in this analysis, accounting for as high as 37.6% 

of all reported tumors in Egyptian females to as low as 27.7% 

of all reported tumors in Israeli Arab females (Table 8.1). Agestandardized incidence rates (ASRs) per 100,000 females were 

highest among Israeli Jews (93.1), similar to the rates reported in 

US SEER females (97.2). These rates were significantly higher than 

those reported in Cypriot (57.7), Egyptian (49.6), Jordanian (38.0 ), 

and Israeli Arab (36.7) females. The high incidence rates described 

in Israeli Jews were similar to those described in North American 

and West European countries, while the lower rates in the other 
 MECC Monograph 75

Breast Cancer Chapter 8

Middle Eastern groups were more similar to rates in Mediterranean 

Europe, Eastern Europe, and some of Asia and Africa [41]. 

Male breast cancer was a relatively rare disease, responsible for 

only 0.2%-0.5% of all malignancies in males in all registries 

(MECC and US SEER) (see Table 1.6). Nevertheless, the agestandardized rate in Israeli Jewish males (1.1) was almost 40% 

higher than the rates reported by the US SEER program or the 

Egyptian registry (0.8) (see Table 1.7).

Age 

Marked differences are noted between age-specific breast cancer 

rates in participating registries. Age-specific rates in almost all age 

groups were highest in the Israeli Jewish population (Table 8.2). 

These rates were higher than the US SEER rates in the age groups 

35-54 years and were similar to or slightly lower than the US rates 

for the older age groups. Age-specific rates in females 25-34 years 

were highest in the Egyptian registry and substantially lower in the 

Jordanian and Israeli Arab populations. While between 57% and 

68% of all breast cancers in the Arab populations of Egypt, Jordan, 

and Israel were diagnosed before the age of 55 years, only about 

44% of the breast cancers among Cypriots and 37% among Israeli 

Jews were diagnosed in that age group. The Israeli Jewish figure was 

again much closer to the US SEER figure of 35% (Figure 8.1). 

Histology

As shown in Table 8.3, microscopic confirmation was available for 

the vast majority of the registered malignancies, ranging from 92.0% 

to 99.4%, with small differences between the participating countries. 

Classification of tumors into specific histological subgroups was 

available for 98.6% of the tumors with microscopic diagnosis in 

Cypriots, 94.2% in Israeli Jews, 91.5% in Israeli Arabs, 91.3% in 

Egyptians, and 90.7% in Jordanians, as compared with 98.7% of the 

tumors in the SEER program. Thus, in all of the MECC registries, 

less than 10% of the microscopically confirmed breast cancers were 

identified as neoplasm or carcinoma only.

The leading tumor histology in all registries was infiltrating duct 

carcinoma, followed by lobular carcinoma (Table 8.3). In the SEER 

program, more infiltrating duct carcinomas were registered with a 

Table 8.1. Breast Cancer: Female Breast Cancer Indicators in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER 

– 1996-2001

Cyprus Israel (Jews) Israel (Arabs) Egypt Jordan US SEER*

1998-2001 1996-2001 1996-2001 1999-2001 1996-2001 1999-2001

Number of incident female breast cancer 

cases 1,066 17,325 762 1,945 2,930 78,802

Breast cancer as proportion of all 

reported tumors in females 35.4% 31.5% 27.7% 37.6% 32.5% 32.3%

Female breast cancer age-standardized 

incidence rates†

57.7 93.1 36.7 49.6 38.0 97.2

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

†Rates are per 100,000 females and are age-standardized to the World Standard Million.
76 MECC Monograph 

Breast Cancer Chapter 8

Table 8.2. Breast Cancer: Age-Standardized and Age-Specific Incidence Rates among Females in 

Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001*

Cyprus 

1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs)

1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER†

1999-2001

Total rate‡ 57.7 93.1 36.7 49.6 38.0 97.2

Age Groups (Rates)§

00-04 y 0.0 0.0 0.0 0.0 0.0 0.0

05-09 y 0.0 0.0 0.0 0.0 0.0 0.0

10-14 y 0.0 - 0.0 0.0 0.0 0.1

15-19 y 0.0 0.3 0.0 - - 0.2

20-24 y - 1.7 0.0 1.4 0.8 1.3

25-29 y 4.9 9.5 8.7 9.8 5.7 7.1

30-34 y 27.2 27.8 11.8 28.9 20.8 25.2

35-39 y 43.5 69.5 35.2 63.6 47.1 61.7

40-44 y 96.3 124.4 53.4 96.7 73.6 117.5

45-49 y 148.8 205.9 93.5 144.9 82.6 192.1

50-54 y 185.8 275.3 104.2 171.5 129.3 253.1

55-59 y 166.7 310.1 124.0 181.2 114.6 332.4

60-64 y 198.3 346.8 144.0 144.2 134.8 386.8

65-69 y 195.1 359.1 136.8 105.0 131.1 431.1

70-74 y 225.4 405.1 118.7 94.1 103.0 458.7

75+ y 203.7 379.9 96.4 99.6 77.6 458.7

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Rates are per 100,000 females and are age-standardized to the World Standard Million.

§Rates are per 100,000 females.

lobular component than in the MECC region registries. Betweencountry differences were noted mainly in the proportion of lobular 

carcinomas and adenocarcinomas.

DISCUSSION

The main finding in these data is the high incidence rate of breast 

cancer in Israeli Jews, compared with a low rate in Arab populations 

and an intermediate rate in Cypriots. While the proportion of all 

cases occurring in younger ages was higher among the Arabs, the 

age-specific rates in practically all age groups were highest in the 

Israeli Jewish population. A younger age distribution of the cases 

in Arab populations is a reflection of the younger demographic 

profile. The use of age-specific rates corrects for this demographic 

difference. It is of interest, however, that the rates in the very young 

age groups in Egyptians, but not in Jordanians or Israeli Arabs, were 

similar to the rates in Israeli Jews, which are among the highest in 
 MECC Monograph 77

Breast Cancer Chapter 8

the world. Given the fact that the Egyptian registry covers 

only part of the Egyptian population, a remote possibility that 

some of these rates reflect a selection into the study cohort of 

younger women cannot be ignored. Nevertheless, a study of 

immigrants from the Middle East to Australia did indicate that 

the Egyptian women had the highest breast cancer rates of all 

Middle Eastern immigrants [42].

These differences in incidence rates provide an example 

of the potential role of lifestyle and genetic factors in 

breast cancer etiology. As the Arab and Jewish populations 

differ dramatically with respect to most of the important 

hormonal risk factors (number of children, total length of 

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

 Cyprus 

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

 Egypt 

1999-2001

 Jordan 

1996-2001

 US SEER* 

1999-2001

Under 35 35-44 45-54 55-64 65-74 75+

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

Figure 8.1. Breast Cancer: Proportions of New Cases by Age Group in Cyprus, Israel (Jews and Arabs), 

Egypt, Jordan, and US SEER � 1996-2001

Proportions

breastfeeding, age at first birth, use of external hormones) as 

well as with respect to diet [43], it is not surprising that such 

large differences in incidence are evident. Studies comparing the 

etiology of breast and colon cancers in Jewish and Arab women 

in Israel have shown major differences in the number of births 

and prevalence of breastfeeding between the 2 demographic 

groups and between cases and controls within each of the 

groups. A major cohort effect has also been observed, with the 

Israeli Arab population moving toward the behaviors of the 

Israeli Jewish population (lower number of children and less 

breastfeeding in the younger cohort). Still, breastfeeding in the 

Arab populations is highly prevalent and is seen as required by 

Islam [44]. A study in Jordan has indicated that obesity was the 

only risk factor, of those studied, that was significantly different 

between women with breast cancer and healthy controls [45]. 

The Mediterranean diet – with high consumption of fruits, 

vegetables, and olive oil, and low consumption of red meat – is 

the staple of most Arab populations and is usually correlated 

with reduced risk of several types of cancer, among them breast 

cancer [46-49]. 

About 10% of all breast cancers in the large Ashkenazi Jewish 

population carry founder mutations in the BRCA genes. The high 

prevalence of these mutations in the Jewish population is at least 

partially responsible for the exceptionally high incidence rates in 

the younger Jewish age groups. It is also potentially responsible 

for the slightly higher proportion of lobular tumors as well as for 

the higher breast cancer rate in Jewish males (due to the founder 

mutation 6174delT in BRCA2). Such high-prevalence founder 

mutations have not been described in the Arab population [50-

52]. Mutations described in the Cypriot population are rare [53]. 

Another possible contributing factor to the observed differences 

in breast cancer rates between Jordan and Egypt and Israel is the 

difference in screening practices between the countries, although 

the impact of such a difference is only temporary. Israel has been 

employing a nationwide, full-coverage mammography screening 
78 MECC Monograph 

Breast Cancer Chapter 8

Table 8.3. Breast Cancer: Proportions of Microscopic Confirmation and Histologic Type of Female Breast 

Cancers in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001

Cyprus

 1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs) 

1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER*

 1999-2001

Total cases microscopically 

confirmed 1,062 16,104 718 1,842 2,956 78,489

Microscopically confirmed 98.7% 92.0% 92.9% 99.4% 93.5% 98.9%

Distribution of Microscopically Confirmed Cases

Histologic distribution† 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Unspecified: Neoplasm, carcinoma1 1.4% 5.8% 8.5% 8.7% 9.3% 1.3%

Specified histologic type 98.6% 94.2% 91.5% 91.3% 90.7% 98.7%

Distribution of Microscopically Confirmed and Specified Cases

Microscopically confirmed and 

specified 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

 Infiltrating duct carcinoma2 80.7% 77.5% 78.1% 84.7% 81.8% 70.2%

 Lobular carcinoma3 7.3% 9.7% 8.5% 5.3% 7.4% 8.4%

 Infiltrating duct and lobular

 carcinoma4 2.3% 2.7% 3.7% 2.8% 1.8% 8.8%

 Adenocarcinoma5 7.4% 5.3% 3.5% 1.3% 4.7% 6.9%

 Medullary carcinoma6 0.3% 1.1% 0.9% 1.0% 1.5% 0.7%

 All other 2.0% 3.7% 5.3% 4.9% 2.8% 5.0%

ICD-O-3 codes

1

8000,8001,8010,8020,8021,8230

2

8500,8521,8541

3

8520

4

8522

5

8050,8140,8211,8260,8401,8480,8481,8490,8503

6

8510 

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

†Percentages should sum over a column to 100% (with some rounding). Where a percentage has been suppressed because it is based on only 1 or 2 cases, the remaining percentages 

will not sum to 100%.

program in women over the age of 50 since 1996. Organized 

screening usually results in a temporary increase in incidence 

rates. Given the length of time it took to achieve a high screening 

prevalence, this temporary effect could have an impact for a period 

of about 10 years.

SUMMARY AND CONCLUSIONS 

Breast cancer rates in the Middle East registries included in this 

analysis express a unique picture of the Israeli Jewish population 

having one of the highest rates worldwide, and the neighboring Arab 

populations having some of the lower world rates. Such a major 

difference between populations living in a relatively small area 
 MECC Monograph 79

Breast Cancer Chapter 8

emphasizes the importance of both lifestyle and genetic factors in 

the causation of breast cancer. It is very important to evaluate the 

prevalence of risk habits in the area populations and to correlate 

these exposures with noted differences in incidence. This will allow 

for a better understanding of the optimal way to combat breast 

cancer in low- and high-incidence populations.

REFERENCES

[1] Althuis MD, Dozier JM, Anderson WF, Devesa SS, Brinton LA. Global 

trends in breast cancer incidence and mortality 1973-1997. Int J Epidemiol 2005;34:405-12.

[2] Yang L, Parkin DM, Ferlay J, Li L, Chen Y. Estimates of cancer incidence 

in China for 2000 and projections for 2005. Cancer Epidemiol Biomarkers 

Prev 2005;14:243-50.

[3] Martin AM, Weber BL. Genetic and hormonal risk factors in breast cancer. J Natl Cancer Inst 2000;92:1126-35.

[4] ESHRE Capri Workshop Group. Hormones and breast cancer. Hum Reprod Update 2004;10:281-93.

[5] Ronckers CM, Erdmann CA, Land CE. Radiation and breast cancer: a 

review of current evidence. Breast Cancer Res 2005;7:21-32.

[6] Carmichael A, Sami AS, Dixon JM. Breast cancer risk among the survivors of atomic bomb and patients exposed to therapeutic ionising radiation. Eur J Surg Oncol 2003;29:475-9.

[7] Albrektsen G, Heuch I, Hansen S, Kvale G. Breast cancer risk by age at 

birth, time since birth and time intervals between births: exploring interaction effects. Br J Cancer 2005;92:167-75.

[8] Lipworth L, Bailey LR, Trichopoulos D. History of breast-feeding in relation to breast cancer risk: a review of the epidemiologic literature. J Natl 

Cancer Inst 2000;92:302-12.

[9] Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer 

and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast 

cancer and 96973 women without the disease. Lancet 2002;360:187-95.

[10] Beral V, Bull D, Doll R, Peto R, Reeves G, Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83,000 

women with breast cancer from 16 countries. Lancet 2004;363:1007-16.

[11] Beral V, Million Women Study Collaborators. Breast cancer and hormonereplacement therapy in the Million Women Study. Lancet 2003;362:419-

27.

[12] Bergkvist L, Adami HO, Persson I, Hoover R, Schairer C. The risk of 

breast cancer after estrogen and estrogen-progestin replacement. N Engl J 

Med 1989;321:293-7.

[13] Hulley S, Furberg C, Barrett-Connor E, Cauley J, Grady D, Haskell W, 

et al. Noncardiovascular disease outcomes during 6.8 years of hormone 

therapy: Heart and Estrogen/progestin Replacement Study follow-up 

(HERS II). JAMA 2002;288:58-66.

[14] Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer 

and hormonal contraceptives: collaborative reanalysis of individual data 

on 53 297 women with breast cancer and 100 239 women without breast 

cancer from 54 epidemiological studies. Lancet 1996;347:1713-27.

[15] Gauthier E, Paoletti X, Clavel-Chapelon F. Breast cancer risk associated with being treated for infertility: results from the French E3N cohort 

study. Hum Reprod 2004;19:2216-21.

[16] Burkman RT, Tang MT, Malone KE, Marchbanks PA, McDonald JA, 

Folger SG, et al. Infertility drugs and the risk of breast cancer: findings 

from the National Institute of Child Health and Human Development 

Women’s Contraceptive and Reproductive Experiences Study. Fertil Steril 

2003;79:844-51.

[17] Wang J, Costantino JP, Tan-Chiu E, Wickerham DL, Paik S, Wolmark 

N. Lower-category benign breast disease and the risk of invasive breast 

cancer. J Natl Cancer Inst 2004;96:616-20.

[18] Vogel VG. Atypia in the assessment of breast cancer risk: implications for 

management. Diagn Cytopathol 2004;30:151-7.

[19] Cho E, Spiegelman D, Hunter DJ, Chen WY, Stampfer MJ, Colditz GA, et 

al. Premenopausal fat intake and risk of breast cancer. J Natl Cancer Inst 

2003;95:1079-85.

[20] Velie E, Kulldorff M, Schairer C, Block G, Albanes D, Schatzkin A. 

Dietary fat, fat subtypes, and breast cancer in postmenopausal women: a 

prospective cohort study. J Natl Cancer Inst 2000;92:833-9.

[21] Key TJ, Appleby PN, Reeves GK, Roddam A, Dorgan JF, Longcope C, 

et al. Body mass index, serum sex hormones, and breast cancer risk in 

postmenopausal women. J Natl Cancer Inst 2003;95:1218-26.
80 MECC Monograph 

Breast Cancer Chapter 8

[22] Harvie M, Howell A, Vierkant RA, Kumar N, Cerhan JR, Kelemen LE, et 

al. Association of gain and loss of weight before and after menopause with 

risk of postmenopausal breast cancer in the Iowa women’s health study. 

Cancer Epidemiol Biomarkers Prev 2005;14:656-61.

[23] Patel AV, Callel EE, Bernstein L, Wu AH, Thun MJ. Recreational physical 

activity and risk of postmenopausal breast cancer in a large cohort of US 

women. Cancer Causes Control 2003;14:519-29.

[24] Zhang S, Hunter DJ, Forman MR, Rosner BA, Speizer FE, Colditz GA, et 

al. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. 

J Natl Cancer Inst 1999;91:547-56.

[25] Fares FA, Ge X, Yannai S, Rennert G. Dietary indole derivatives induce 

apoptosis in human breast cancer cells. Adv Exp Med Biol 1998;451:153-

7.

[26] McDonald JA, Mandel MG, Marchbanks PA, Folger SG, Daling JR, 

Ursin G, et al. Alcohol exposure and breast cancer: results of the women’s 

contraceptive and reproductive experiences study. Cancer Epidemiol Biomarkers Prev 2004;13:2106-16.

[27] Collaborative Group on Hormonal Factors in Breast Cancer. Alcohol, 

tobacco and breast cancer–collaborative reanalysis of individual data from 

53 epidemiological studies, including 58,515 women with breast cancer 

and 95,067 women without the disease. Br J Cancer 2002;87:1234-45.

[28] Reynolds P, Hurley S, Goldberg DE, Anton-Culver H, Bernstein L, 

Deapen D, et al. Active smoking, household passive smoking, and breast 

cancer: evidence from the California Teachers Study. J Natl Cancer Inst 

2004;96:29-37.

[29] Engel LS, Hill DA, Hoppin JA, Lubin JH, Lynch CF, Pierce J, et al. Pesticide use and breast cancer risk among farmers’ wives in the agricultural 

health study. Am J Epidemiol 2005;161:121-35.

[30] Coyle YM. The effect of environment on breast cancer risk. Breast Cancer 

Res Treat 2004;84:273-88.

[31] Calle EE, Frumkin H, Henley SJ, Savitz DA, Thun MJ. Organochlorines 

and breast cancer risk. CA Cancer J Clin 2002;52:301-9.

[32] Kerlikowske K, Shepherd J, Creasman J, Tice JA, Ziv E, Cummings SR. 

Are breast density and bone mineral density independent risk factors for 

breast cancer? J Natl Cancer Inst 2005;97:368-74.

[33] Szabo CI, King MC. Population genetics of BRCA1 and BRCA2. Am J 

Hum Genet 1997;60:1013-20.

[34] Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, 

et al. The risk of cancer associated with specific mutations of BRCA1 and 

BRCA2 among Ashkenazi Jews. N Engl J Med 1997;336:1401-8.

[35] Anglian Breast Cancer Study Group. Prevalence and penetrance of 

BRCA1 and BRCA2 mutations in a population-based series of breast 

cancer cases. Br J Cancer 2000;83:1301-8.

[36] Hopper JL, Southey MC, Dite GS, Jolley DJ, Giles GG, McCredie MR, 

et al. Population-based estimate of the average age-specific cumulative 

risk of breast cancer for a defined set of protein-truncating mutations in 

BRCA1 and BRCA2. Australian Breast Cancer Family Study. Cancer 

Epidemiol Biomarkers Prev 1999;8:741-7.

[37] Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, et al. 

Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 

genes in breast cancer families. Am J Hum Genet 1998;62:676-89.

[38] Rennert G, Dishon S, Rennert HS, Fares F. Phenotypic characteristics of 

families with BRCA1 and BRCA2 mutations in Israel. Eur J Cancer Prev 

2005;14:357-61.

[39] Chlebowski RT, Chen Z, Anderson GL, Rohan T, Aragaki A, Lane D, et 

al. Ethnicity and breast cancer: factors influencing differences in incidence 

and outcome. J Natl Cancer Inst 2005;97:439-48.

[40] Bernstein L, Teal CR, Joslyn S, Wilson J. Ethnicity-related variation in 

breast cancer risk factors. Cancer 2003;97:222-9.

[41] Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in 

five continents, volume VIII. IARC Scientific Publication No. 155. Lyon 

(France): International Agency for Research on Cancer; 2002.

[42] McCredie M, Coates M, Grulich A. Cancer incidence in migrants to New 

South Wales (Australia) from the Middle East, 1972-91. Cancer Causes 

Control 1994;5:414-21.

[43] Shakour SK, Almog R, Gruber SB, Low M, Pinchev M, Reisfeld D, et 

al. Reproductive risk factors for breast and colorectal cancers in the Arab 

population in Israel (abstract). Cairo (Egypt): Conference on Cancer in 

Developing Countries; 2005.

[44] Hawwas AW. Breast feeding as seen by Islam. Popul Sci 1987;7:55-8.

[45] Atoum MF, Al Hourani HM. Lifestyle related risk factors for breast cancer in Jordanian females. Saudi Med J 2004;25:1245-8.

[46] Trichopoulou A, Lagiou P, Kuper H, Trichopoulos D. Cancer and Mediterranean dietary traditions. Cancer Epidemiol Biomarkers Prev 2000;9:869-

73.
 MECC Monograph 81

Breast Cancer Chapter 8

[47] Alarcon de la Lastra C, Barranco MD, Motilva V, Herrerias JM. Mediterranean diet and health: biological importance of olive oil. Curr Pharm Des 

2001;7:933-50.

[48] Menendez JA, Vellon L, Colomer R, Lupu R. Oleic acid, the main 

monounsaturated fatty acid of olive oil, suppresses Her-2/neu (erbB-2) 

expression and synergistically enhances the growth inhibitory effects of 

trastuzumab (Herceptin) in breast cancer cells with Her-2/neu oncogene 

amplification. Ann Oncol 2005;16:359-71.

[49] Nelson R. Oleic acid suppresses overexpression of ERBB2 oncogene. 

Lancet Oncol 2005;6:69.

[50] Atoum MF, Al Kayed SA. Mutation analysis of the breast cancer gene 

BRCA1 among breast cancer Jordanian females. Saudi Med J 2004;25:60-

3.

[51] El Harith e, Abdel-Hadi MS, Steinmann D, Dork T. BRCA1 and BRCA2 

mutations in breast cancer patients from Saudi Arabia. Saudi Med J 

2002;23:700-4.

[52] Bedwani R, Abdel-Fattah M, El Shazly M, Bassili A, Zaki A, Seif HA, et 

al. Profile of familial breast cancer in Alexandria, Egypt. Anticancer Res 

2001;21:3011-4.

[53] Hadjisavvas A, Charalambous E, Adamou A, Neuhausen SL, Christodoulou CG, Kyriacou K. Hereditary breast and ovarian cancer in Cyprus: 

identification of a founder BRCA2 mutation. Cancer Genet Cytogenet 

2004;151:152-6.
82 MECC Monograph 
 MECC Monograph 83

Cervical and Corpus Uterine Cancer Chapter 9

CHARITINI KOMODIKI

BACKGROUND 

Cervical Cancer

Cervical uterine cancer – referred to in this chapter as cervical 

cancer – is the second most common form of cancer among women 

worldwide, with an estimated 493,000 new cases (as compared 

with 1.15 million new cases of breast cancer) and 274,000 deaths 

(as compared with 411,000 deaths from breast cancer) in 2002. In 

general terms, cervical cancer is much more common in developing 

countries, in which it accounts for 15% of all new female cancers, 

whereas in developed countries it accounts for only 3.6% of such 

cases [1].

In parts of Asia, Africa, and South America, cervical cancer is the 

most common form of malignant disease in females and is becoming 

a major cause of morbidity and mortality throughout the developing 

world. In the United Kingdom, Europe, North America, and Japan, 

cancers of the female reproductive system in general are less 

frequent than breast and gastrointestinal malignancies.

The worldwide differences in cervical cancer incidence are due, 

at least in part, to socioeconomic and behavioral differences 

across nations. Substantial declines in incidence and mortality of 

cervical cancer in Western countries have resulted mainly from 

comprehensive screening programs that have been implemented in 

the developed countries over the last decades.

Corpus Cancer

Corpus uterine cancer (sometimes referred to as endometrial 

cancer, and referred to in this chapter as corpus cancer) has a 

similar geographic distribution to that of ovarian cancer. The 

highest incidence is found in North America, with age-standardized 

incidence rates (ASRs) of around 18 per 100,000 in US Whites 

and around 15 in Canadians. ASRs are also quite high in Europe, 

particularly in Eastern European countries such as the Czech 

Republic, Slovakia, and Latvia, where rates are comparable to those 

in US Whites. Rates are low (generally less than 6) in southern and 

eastern Asia (including Japan) and in most of Africa [2]. 

Corpus cancer appears more important as a cause of morbidity 

(199,000 new cases per annum, or 3.9% of cancers in women) 

than as a cause of mortality (50,000 deaths per annum, or 1.7% of 

cancer deaths in women) [1]. This is because corpus cancer carries 

a relatively favorable prognosis. Survival rates are rather high and 

slightly higher than for breast cancer – 89% for corpus cancer 

versus 81% for breast cancer in the United States, and 83% versus 

74%, respectively, in Western Europe. The proportion of corpus 

cancer patients surviving up to 5 years in developing countries 

is lower than in developed countries (for example, 70% in South 

America and 69% in Eastern Europe), but still somewhat higher than 

for breast cancer patients (67% and 58%, respectively) [1]. 

Part of the reason for these worldwide differences is that corpus 

cancer risk is related to prolonged high estrogen hormone levels, and 

these are more prevalent in developed countries, where women bear 

fewer children and are more likely to take hormone replacement 

therapy (HRT). 

Etiology

Cervical Cancer

The risk of developing cervical cancer is associated with human 

papillomavirus (HPV) infections. Different types of HPV have been 

associated with different histologies, such as HPV type 16 with 

squamous cell carcinoma, and type 18 with adenocarcinoma. 
84 MECC Monograph 

Cervical and Corpus Uterine Cancer Chapter 9

In the 1990s, extensive research showed that HPV infection 

causes virtually all cases of cervical cancer. Bosch et al. [3] found 

HPV DNA in nearly all cervical cancers. Schiffman et al. [4]

concentrated on precursors of cervical cancer. To confirm the strong 

association between oncogenic HPV and cervical cancer, a number 

of prospective studies were completed, including a 20,000-woman 

cohort in Oregon [5], a 10,000-woman cohort in Costa Rica [6], and 

similarly large studies in England [7], Brazil [8], Denmark [9], and 

California [10]. 

Currently, epidemiological studies have revealed not only that 

women without HPV do not develop cervical cancer, but also that 

neither do most women with HPV. A new generation of biomarkers 

should be investigated [11].

Early onset of sexual activity, multiple sexual partners, smoking, 

and low socioeconomic status are associated with development of 

cervical cancer. A number of studies conducted in Denmark [12]

showed that possible risk factors for cervical neoplasia in HPVpositive women included smoking, non-use of barrier contraceptives, 

and larger number of children born. According to results of a case 

control study [13] in Sweden, smoking appeared to be the most 

significant environmental risk factor for cervical cancer.

Smith et al. [14] suggested that herpes simplex virus-2 may act 

in the presence of HPV infection to increase the risk of invasive 

cervical carcinoma. 

Corpus Cancer

Risk factors for corpus cancer can be classified as (1) endogenous, 

with prolonged high estrogen levels, and (2) exogenous.

Endogenous risk factors include obesity, early menarche, late 

menopause, low parity, polycystic ovary syndrome, estrogensecreting tumors, and family history, particularly the Lynch type 

II syndrome. The data are inconclusive for diabetes mellitus and 

immune deficiency.

Exogenous risk factors include noncyclical estrogen replacement 

therapy, tamoxifen therapy, sequential oral contraception, diet, and 

previous radiation therapy.

The most well-established risk factors are associated with prolonged 

high estrogen levels, either due to natural causes, like nulliparity, 

or to artificial causes, such as postmenopausal estrogens. Beral et 

al. [15] in their review reported that almost 100 epidemiological 

studies found a relationship between the use of HRT and the risk of 

cancer of the female reproductive organs, namely the breast, uterus, 

or ovary. The risk increases with increasing duration of use. Bakken 

et al. [16] in their study in a Norwegian cohort of women found 

no significant increase in risk of corpus cancer. Factors that raise 

endogenous estrogen levels, such as obesity and consumption of 

processed meat and fish, are also associated with increased risk.

Combined oral contraception, cigarette smoking, and high parity are 

considered as protective factors against corpus cancer [17]. 

RESULTS

Cervical Cancer 

Among the MECC countries, the highest ASR of cervical cancer 

was observed in Israeli Jews (5.3), followed by Cypriots (3.7), 

Egyptians (2.7), Jordanians (2.6), and Israeli Arabs (2.5). The US 

SEER rate (7.0) was higher than for any MECC registry (Table 9.1). 

This could be attributed mainly to differences in sexual activity. The 

implementation of successful cervical cancer screening programs in 

most developed countries may, in the short term, reveal more cases, 

but would not in the long term account for a higher incidence. 
 MECC Monograph 85

Cervical and Corpus Uterine Cancer Chapter 9

Table 9.1. Cervical and Corpus Uterine Cancer: Number of Cases, Age Distribution, and 

Age-Standardized Incidence Rates,* by Age, among Females in Cyprus, Israel (Jews and 

Arabs), Egypt, Jordan, and US SEER − 1996-2001†

Cyprus

1998-2001

Israel 

(Jews) 

1996-2001

Israel 

(Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER‡

1999-2001

Total cases - Cervical cancer 70 922 54 96 194 5,284

Total cases - Corpus cancer and uterine 

cancer, NOS§ 225 2,645 161 124 405 14,129

Age Groups (Distribution)

Cervical cancer

<30 y - 2.5% - - 2.1% 6.4%

30-49 y 37.1% 44.8% 46.3% 36.5% 44.3% 48.4%

50-69 y 30.0% 33.0% 42.6% 52.1% 41.8% 30.2%

70+ y 30.0% 19.7% 9.3% 9.4% 11.9% 15.0%

Corpus cancer and uterine cancer, NOS§

<50 y 9.3% 11.6% 13.7% 33.1% 26.4% 15.5%

50-59 y 25.8% 21.6% 34.2% 27.4% 28.9% 24.4%

60-69 y 34.2% 30.7% 32.3% 29.0% 31.6% 25.5%

70+ y 30.7% 36.2% 19.9% 10.5% 13.1% 34.6%

Age Groups (Rates)*

Cervical cancer

Total rate 3.7 5.3 2.5 2.7 2.6 7.0

<30 y - 0.3 - - 0.0 1.2

30-49 y 6.4 10.9 3.9 3.1 4.0 14.0

50-69 y 8.0 12.4 8.3 9.6 7.6 15.4

70+ y 18.2 13.4 6.6 8.4 9.7 14.2

Corpus cancer and uterine cancer, NOS§

Total rate 11.8 13.8 8.7 3.5 5.8 17.6

<50 y 1.6 2.4 1.0 1.1 1.4 3.7

50-59 y 37.6 42.8 31.7 10.9 16.7 53.7

60-69 y 68.4 72.5 47.5 16.3 32.7 89.7

70+ y 58.6 72.3 43.2 12.5 21.5 88.3

*Rates are per 100,000 females and are age-standardized to the World Standard Million.

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

§NOS indicates “not otherwise specified.”

The higher incidence rate observed in Israeli Jews was similar to 

that observed in Japan (Miyaki), Kuwait, Italy (Ragusa Province, 

Sassari, Umbria, Venetian region), Switzerland (Geneva), and Spain 

(Saragosa), while the low rate observed in Israeli Arabs was similar 

to that observed in some parts of China (Beijing, Shanghai, Tianjin). 

It is interesting to note that the highest rates of cervical cancer 

– observed in Zimbabwe, Harare (55.04) and Uganda (41.73) – are 

both far in excess of the rates reported in the MECC populations. On 

the other hand, in some parts of China (Changie, Cixion) no cases 

have been found [2].

Corpus Cancer and Uterine Cancer Not Otherwise Specified 

Among the MECC countries, the highest rate for corpus cancer 

and uterine cancer not otherwise specified (NOS) was observed 

in Israeli Jews (13.8), followed by Cypriots (11.8), Israeli Arabs 

(8.7), Jordanians (5.8), and Egyptians (3.5). In US SEER, the 

rate was much higher (17.6) (Table 9.1). The disparity between 

the rates in these populations could be attributed to differences 

in socioeconomic and behavioral factors, such as the number of 

children born and the use of HRT.

The higher ASRs observed in Israeli Jews and Cypriots were similar 

to those observed in other countries, such as New Zealand, Australia, 

Canada, Uruguay, Austria (Tyrol), France, Netherlands, Denmark, 

Switzerland, United Kingdom, Spain, and parts of Italy. In Asian 

countries like India, China, Thailand, Oman, Kuwait, and parts of 

Japan, ASRs below 5.0 were observed, similar to those observed in 

Jordan and Egypt [2].

It should be noted that rates of corpus cancer were higher than for 

cervical cancer for all the registries in this MECC report. 
86 MECC Monograph 

Cervical and Corpus Uterine Cancer Chapter 9

Figure 9.1. Cervical Cancer: Age Distribution by Country in Cyprus, Israel (Jews and Arabs), 

Egypt, Jordan, and US SEER – 1996-2001

0

10

20

30

40

50

60

70

80

90

100

Cyprus 

1998-2001

Israel (Jews)

1996-2001

Israel (Arabs)

1996-2001

 Egypt 

1999-2001

 Jordan 

1996-2001

US SEER*

1999-2001

70+

50-69

30-49

<30

Age

Percent

* SEER 13 Registries, Public Use Data Set, from data submitted November 2004. Figure 9.2. Cervical Cancer: Age-Standardized Incidence Rates* by Country and Age in Cyprus, 

Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001

0

5

10

15

20

 Cyprus 

1998-2001

Israel (Jews)

1996-2001

Israel (Arabs)

1996-2001

 Egypt 

1999-2001

 Jordan 

1996-2001

 US SEER† 

1999-2001

<30

30-49

50-69

70+

Age

Rate per 100,000

*Rates are per 100,000 and are age-standardized to the World Standard Million.

† SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

Overall Age Distribution

Cervical Cancer

In all MECC countries and US SEER, the proportion of 

cervical cancer diagnosed under the age of 30 years was 

low. However, the proportion in the MECC registries (about 

2%) did appear to be lower than in US SEER (6.4%). This 

may be explained by the well-established cervical cancer 

screening program in the United States, which contributes 

to the diagnosis of cases at an earlier age. The highest 

percentages of cases were in the age group 30-49 years, 

except in Egypt, where over half the cases were in females 

aged 50-69 years, compared with 36.5% of those aged 30-

49 years. In Cyprus, a higher percentage of cases occurred 

in those aged 70 years and above (30.0%), compared with the 

other registries (Table 9.1 and Figure 9.1). 

Just as the percentage of cervical cancer cases below the age of 

30 years was very low, so were the incidence rates in this age 

group (Table 9.1). In Cypriots, Israeli Jews, and Jordanians, the 

ASR was highest for ages 70 and above, while in Egyptians, 

Israeli Arabs, and the US SEER population, the rate was 

highest in the age group 50-69 years. In the age group 70 years 

and above, the rate was highest in Cypriots (Table 9.1 and 

Figure 9.2). 
 MECC Monograph 87

Cervical and Corpus Uterine Cancer Chapter 9

Figure 9.4. Corpus Cancer and Uterine Cancer NOS*: Age-Standardized Incidence Rates† by 

Country and Age in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER‡ – 1996-2001

0

10

20

30

40

50

60

70

80

90

100

 Cyprus 

1998-2001

Israel (Jews)

1996-2001

Israel (Arabs)

1996-2001

 Egypt 

1999-2001

 Jordan 

1996-2001

 US SEER‡ 

1999-2001

<50

50-59

60-69

70+

Age

Rate per 100,000

*NOS indicates not otherwise specified.

†Rates are per 100,000 and are age-standardized to the World Standard Million.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

Figure 9.3. Corpus Cancer: Age Distribution by Country in Cyprus, Israel (Jews and Arabs), 

Egypt, Jordan, and US SEER* – 1996-2001

0

10

20

30

40

50

60

70

80

90

100

 Cyprus 

1998-2001

Israel (Jews)

1996-2001

Israel (Arabs)

1996-2001

 Egypt 

1999-2001

 Jordan 

1996-2001

 US SEER* 

1999-2001

70+

60-69

50-59

<50

Age

Percent

*SEER 13 registries, Public Use Data Set, from data submitted November 2004.

Corpus Cancer and Uterine Cancer Not Otherwise Specified

The percentage of cases below the age of 50 years for corpus 

cancer and uterine cancer NOS was highest in Egyptians (33.1%) 

and Jordanians (26.4%). In Israeli Arabs, the disease was most 

commonly diagnosed in the age group 50-59 years; in Cypriots, 

Egyptians, and Jordanians, in the age group 60-69 years; and in 

Israeli Jews and US SEER, in the age group 70 years and above. 

Higher percentages of cases in this age group were found in Israeli 

Jews (36.2%), Cypriots (30.7%), and US SEER (34.6%) (Table 9.1 

and Figure 9.3). 

In each age group, incidence rates were highest in US SEER, 

followed by those in Israeli Jews and in Cypriots (Table 9.1 and 

Figure 9.4). 

Histology of the Microscopically Confirmed Cases

Cervical Cancer

The majority of cervical cancers in all the registries were squamous 

cell carcinoma, with the lowest percentage (67.8%) in Israeli Jews 

and the highest percentage (82.6%) in Cypriots. Almost one-fifth 

of cases (ranging from 15.8% in Egypt to 22.9% in US SEER) were 

found to be adenocarcinoma (Table 9.2). 
88 MECC Monograph 

Cervical and Corpus Uterine Cancer Chapter 9

Table 9.2. Cervical and Corpus Uterine Cancer: Number of Cases and Proportions of Histologic Distribution among Females in 

Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001*

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Total cases - Cervical cancer 69 854 47 95 193 5,222

Total cases - Corpus cancer 217 2,169 136 53 215 13,768

Total cases - Uterine cancer, NOS‡ 7 336 16 50 186 205

Cervical Cancer 

Adenocarcinoma 15.9% 22.6% 17.0% 15.8% 20.7% 22.9%

Squamous cell carcinoma 82.6% 67.8% 76.6% 71.6% 68.4% 70.0%

Other histologies - 9.6% 6.4% 12.6% 10.9% 7.0%

Corpus Cancer

Adenocarcinoma 87.1% 87.5% 88.2% 83.0% 76.7% 88.6%

Squamous cell carcinoma 2.3% 0.9% - 0% 1.9% 0.4%

Other histologies 10.6% 11.7% 10.3% 17.0% 21.4% 10.9%

Uterine Cancer, NOS‡

Adenocarcinoma 42.9% 60.7% 75.0% 50.0% 50.0% 22.9%

Squamous cell carcinoma 0% 3.9% 0% - 6.5% 3.4%

Other histologies 57.1% 35.4% 25.0% 48.0% 43.5% 73.7%

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡NOS indicates “not otherwise specified.”

Corpus Cancer and Uterine Cancer Not Otherwise Specified

The majority of corpus cancers in all the registries were 

adenocarcinoma, with the lowest percentage (76.7%) in Jordanians 

and the highest percentage (88.6%) in US SEER (Table 9.2). Uterine 

cancers NOS were also mostly adenocarcinoma, except among the 

relatively small numberof such cases in the US SEER population.

SUMMARY AND CONCLUSIONS

Cervical Cancer

Cervical cancer is now known to be caused by infection with various 

types of HPV. Early onset of sexual activity, multiple sexual partners, 

smoking, and low socioeconomic status are all associated with the 

disease. 

The highest incidence rates of cervical cancer were found in US 

SEER, followed by Israeli Jews and Cypriots.
 MECC Monograph 89

Cervical and Corpus Uterine Cancer Chapter 9

The proportion of cases diagnosed below age 30 years was very 

low – around 2% in MECC countries, compared with 6.4% in US 

SEER. This may be explained by the well-established cervical 

cancer screening program in the United States, which contributes to 

the diagnosis of cases at an earlier age. Most of the cases in MECC 

countries and US SEER were diagnosed in the age group 30-49 

years, except in Egypt, where most of the cases were diagnosed in 

the age group 50-69 years.

In Cypriots, Israeli Jews, and Jordanians, the ASR was highest for 

ages 70 and above, while in Egyptians, Israeli Arabs, and US SEER, 

the rate was highest in the age group 50-69 years. 

Corpus Cancer

Risk factors for corpus cancer are associated with prolonged high 

estrogen levels. Factors such as low parity and the use of HRT were 

more commonly found in the United States than in MECC countries. 

Corpus cancer was most commonly diagnosed in women older than 50 

years at the time of diagnosis. 

Incidence rates of corpus cancer were higher than those for cervical 

cancer in all of the registries in this study. In each age group, ASRs 

for corpus cancer were highest in US SEER, followed by those in 

Israeli Jews and in Cypriots. The highest rates for corpus cancer 

were observed in the age group 60-69 years in all of the registries. 

REFERENCES

[1] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA 

Cancer J Clin 2005;55:74-108.

[2] Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in 

five continents, volume VIII. IARC Scientific Publication No. 155. Lyon 

(France): International Agency for Research on Cancer; 2002.

[3] Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, et al. 

Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study 

Group. J Natl Cancer Inst 1995;87:796-802.

[4] Schiffman MH, Bauer HM, Hoover RN, Glass AG, Cadell DM, Rush 

BB, et al. Epidemiologic evidence showing that human papillomavirus 

infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst 

1993;85:958-64.

[5] Liaw KL, Glass AG, Manos MM, Greer CE, Scott DR, Sherman M, et al. 

Detection of human papillomavirus DNA in cytologically normal women 

and subsequent cervical squamous intraepithelial lesions. J Natl Cancer 

Inst 1999;91:954-60.

[6] Herrero R, Hildesheim A, Bratti C, Sherman ME, Hutchinson M, Morales 

J, et al. Population-based study of human papillomavirus infection and 

cervical neoplasia in rural Costa Rica. J Natl Cancer Inst 2000;92:464-74.

[7] Deacon JM, Evans CD, Yule R, Desai M, Binns W, Taylor C, et al. Sexual 

behaviour and smoking as determinants of cervical HPV infection and of 

CIN3 among those infected: a case-control study nested within the Manchester cohort. Br J Cancer 2000;83:1565-72.

[8] Franco EL, Villa LL, Sobrinho JP, Prado JM, Rousseau MC, Desy M, et 

al. Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from a high-risk area for cervical cancer. J 

Infect Dis 1999;180:1415-23.

[9] Kjaer SK, van den Brule AJ, Bock JE, Poll PA, Engholm G, Sherman ME, 

et al. Human papillomavirus – the most significant risk determinant of 

cervical intraepithelial neoplasia. Int J Cancer 1996;65:601-6.

[10] Moscicki AB, Hills N, Shiboski S, Powell K, Jay N, Hanson E, et 

al. Risks for incident human papillomavirus infection and low-grade 

squamous intraepithelial lesion development in young females. JAMA

2001;285:2995-3002.

[11] Schiffman MH, Castle P. Epidemiologic studies of a necessary causal 

risk factor: human papillomavirus infection and cervical neoplasia. J Natl 

Cancer Inst 2003;95:E2.

[12] Kjaer SK. Risk factors for cervical neoplasia in Denmark. APMIS Suppl 

1998;80:1-41.
90 MECC Monograph 

Cervical and Corpus Uterine Cancer Chapter 9

[13] Kjellberg L, Hallmans G, Ahren AM, Johansson R, Bergman F, Wadell G, 

et al. Smoking, diet, pregnancy and oral contraceptive use as risk factors 

for cervical intra-epithelial neoplasia in relation to human papillomavirus 

infection. Br J Cancer 2000;82:1332-8.

[14] Smith JS, Herrero R, Bosetti C, Munoz N, Bosch FX, Eluf-Neto J, et al. 

Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer. J Natl Cancer Inst 2002;94:1604-13.

[15] Beral V, Banks E, Reeves G, Appleby P. Use of HRT and the subsequent 

risk of cancer. J Epidemiol Biostat 1999;4:191-210.

[16] Bakken K, Alsaker E, Eggen AE, Lund E. Hormone replacement therapy 

and incidence of hormone-dependent cancers in the Norwegian Women 

and Cancer study. Int J Cancer 2004;112:130-4.

[17] Souhami RL, Tannock I, Hohenberger P, Horiot JC, editors. Oxford textbook of oncology, second edition. Oxford (UK): Oxford University Press; 

2001.
 MECC Monograph 91

Ovarian Cancer Chapter 10

CHARITINI KOMODIKI

BACKGROUND 

The incidence of ovarian cancer is higher in the highly industrial 

countries of the world, particularly in Western and Northern Europe 

and North America [1]. The median age at diagnosis is 62 years. 

Some 85% to 90% of ovarian cancers are epithelial, and more 

than two thirds are diagnosed at an advanced stage. Epithelial 

ovarian cancer is the leading cause of death in females with pelvic 

malignancies.

The etiology of ovarian cancer is poorly understood [2]. The risk of 

ovarian cancer is reduced in women with high parity and in women 

who use oral contraceptives. Full-term and complete pregnancy 

protects against the development of ovarian cancer [3,4]. Oral 

contraceptives that reduce or suppress ovulation, used for 5 years 

or longer, reduce the risk of this cancer by about half. Other factors 

that are associated with a reduced risk are a history of breastfeeding, 

tubal ligation, and hysterectomy [5].

Factors associated with an increased risk for invasive epithelial 

ovarian cancer include older age, race (White), nulliparity, family 

history of ovarian cancer, and a history of endometrial or breast 

cancer [5].

Engeland et al. [6] found a positive association between height and 

risk of ovarian cancer. Riman et al. [7] revealed an increased risk 

of epithelial ovarian cancer with the use of hormone replacement 

therapy with sequentially added progestin and estrogen. 

Women who are single and have low parity and a history of breast 

cancer are at higher risk. The risk of ovarian cancer is usually found 

to be higher in White, affluent, and better-educated societies [5].

The familial risk of ovarian cancer is also well documented [5,8]. 

Patients with BRCA1 and BRCA2 gene mutations have an increased 

risk of ovarian cancer [5].

Childhood infections (such as mumps and rubella), obesity, diet, and 

exposure to radiation and to talc have been linked to ovarian cancer, 

but results are inconsistent [9].

RESULTS

Overall Incidence

As shown in Table 10.1, among the MECC countries, the highest 

age-standardized incidence rate (ASR) of ovarian cancer was 

observed in female Israeli Jews (9.4) (the US SEER rate was 10.0). 

These rates were followed by Cypriots (7.7), Egyptians (5.4), 

Jordanians (4.6), and Israeli Arabs (3.6). In the under-50 age group, 

the rate of ovarian cancer was highest in Israeli Jews and US SEER 

(3.2), followed by Egyptians (2.5), Cypriots and Jordanians (2.1), 

and Israeli Arabs (1.4).

In the age group 50-69 years, the rate was highest in US SEER 

(33.5), followed by Israeli Jews (32.3), Cypriots (27.8), Egyptians 

(17.7), Jordanians (14.1), and Israeli Arabs (10.5) (Figure 10.1).

In the 70+ age group, the rate was highest in US SEER (52.7), 

followed by Israeli Jews (40.9), Cypriots (38.2), Israeli Arabs 

(19.3), Jordanians (17.3), and Egyptians (14.9). The incidence rates 

increased as age increased, with the exception of Egypt, where the 

rate was highest for 50- to 69-year-olds (Figure 10.1).

The differences in these rates conform to the pattern of ovarian 

cancer risk, whereby the cancer more commonly occurs among 
92 MECC Monograph 

Ovarian Cancer Chapter 10

females in developed industrial countries than in less developed 

countries. The highest MECC incidence rate, observed in Israeli 

Jews, can be compared to those rates found in some parts of Canada, 

Austria, France, Poland, Spain, and Italy. The lowest incidence rate, 

in Israeli Arabs, can be compared to rates observed in some parts of 

China, India, and Thailand [10].

Among MECC countries, the higher incidence rates observed 

among Israeli Jews and Cypriots can be explained by the similar 

socioeconomic and cultural environment of the 2 countries, while 

the similar rates among Egyptians, Jordanians, and Israeli Arabs 

can be explained by the similar cultural, ethnic, and genetic 

characteristics in these countries.

Age 

For Cypriots, Israeli Jews, and the US SEER population, the highest 

proportions of ovarian cancer cases were in the 50-69 year age 

group. For Jordanians, Egyptians, and Israeli Arabs, however, the 

highest percentages were in below-50 age group (Figure 10.2).

In US SEER and among Israeli Jews and Cypriots, the percentage 

of cases in the 70+ age group was quite high, while in Egyptians, 

Jordanians, and Israeli Arabs, it was much lower (Figure 10.2).

Histology

As shown in Table 10.2, proportions of microscopic confirmation 

varied widely (from 77.3% to 99.2%) among the registries. 

Comparisons of incidence rates by histology type are therefore 

unreliable. Instead, we compare the distribution of cases by 

histology subtype among microscopically confirmed cases. 

Carcinoma was the most commonly observed type of ovarian 

cancer in all registries, accounting for between 77.8% and 93.2% 

of the cancers. Serous carcinoma was the most commonly observed 

specific type of ovarian carcinoma in all MECC countries. The 

highest percentage of serous carcinoma was observed in Israeli 

Jews (44.9%), which was very close to the percentage in US SEER 

(42.1%), followed by Cypriots (40.6%), Israeli Arabs (36.2%), 

Jordanians (28.7%), and Egyptians (27.2%).

The most common form of ovarian carcinoma, after serous 

carcinoma, was adenocarcinoma. The percentages of 

adenocarcinoma were similar across all registries, ranging from 

14.4% to 18.8%.

The proportion of mucinous carcinoma was higher in Egyptians 

(16.1%) and Jordanians (11.7%) than in the other registries, where 

percentages ranged from 6.0% to 8.7%.

Table 10.1. Ovarian Cancer: Age-Standardized Incidence Rates* by Age among Females in Cyprus, 

Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001

Cyprus

 1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan 1996-

2001

US SEER†

 1999-2001

Total rate 7.7 9.4 3.6 5.4 4.6 10.0

<50 y 2.1 3.2 1.4 2.5 2.1 3.2

50-69 y 27.8 32.3 10.5 17.7 14.1 33.5

70+ y 38.2 40.9 19.3 14.9 17.3 52.7

*Rates are per 100,000 females and are age-standardized to the World Standard Million.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
 MECC Monograph 93

Ovarian Cancer Chapter 10

The proportion of endometroid carcinoma was higher in the Israeli 

Jewish (15.0%) and US SEER populations (12.2%) than in the other 

registries, where percentages ranged from 7.8% to 10.9%.

The proportion of clear cell carcinoma cases was low in Cypriots, 

US SEER, and Israeli Jews, and almost non-existent in the Arab 

populations.

The percentages of other histological types of ovarian cancer were 

rather low. Germ-cell tumors accounted for a larger proportion of 

ovarian cancers in the Arab populations (7.2%-12.1%) than among 

the US SEER, Cypriot, and Israeli Jewish populations (2.2%-3.1%).

The percentage of sex cord-stromal tumors was very low in all 

populations, but particularly in Israeli Arabs and Jews.

SUMMARY AND CONCLUSIONS

US, Israeli Jewish, and Cypriot women had the highest incidence 

of ovarian cancer, while Egyptian, Jordanian, and Israeli Arab 

women had the lowest incidence for the same period. This could be 

attributed to differences in socioeconomic status of the countries, 

which no doubt relate to differences across these populations in 

parity, a major protective factor for ovarian cancer. The incidence 

rate among Israeli Jewish women was 9.4, almost 3 times the rate 

among Israeli Arab women. 

In all MECC countries, the most common histological type of 

ovarian cancer was carcinoma of the ovary. 

Figure 10.1. Ovarian Cancer: Age-Standardized Incidence Rates* by Country and Age 

in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001

3.2 2.1 1.4 2.5 2.1 3.2

27.8

32.3

10.5

17.7

33.5

14.1

38.2

40.9

19.3

14.9

52.7

17.3

0

10

20

30

40

50

60

 Cyprus 

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs) 

1996-2001

 Egypt 

1999-2001

 Jordan 

1996-2001

 US SEER 

1999-2001

<50

50-69

70+

Age

Rate per 100,000

*Rates are per 100,000 and are age-standardized to the World Standard Million.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

†

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

 Cyprus 

1998-2001

Israel (Jews)

1996-2001

Israel (Arabs) 

1996-2001

 Egypt 

1999-2001

 Jordan 

1996-2001

US SEER* 

1999-2001

70+

50-69

<50

Figure 10.2. Ovarian Cancer: Age Distribution by Country in Cyprus, Israel 

(Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
94 MECC Monograph 

Ovarian Cancer Chapter 10

Table 10.2. Ovarian Cancer: Proportions of Microscopic Confirmation and Histologic Type among Females in 

Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001*

Cyprus

 1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER†

1999-2001

Total cases microscopically confirmed 138 1511 58 180 369 7706

Microscopically confirmed 96.5% 86.4% 77.3% 85.7% 99.2% 93.6%

 Distribution

Histologic distribution‡ 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Carcinoma 88.4% 93.2% 84.5% 77.8% 81.0% 91.8%

 Serous carcinoma 40.6% 44.9% 36.2% 27.2% 28.7% 42.1%

 Mucinous carcinoma 8.7% 6.0% 6.9% 16.1% 11.7% 7.5%

 Endometroid carcinoma 10.9% 15.0% 8.6% 7.8% 10.6% 12.2%

 Clear-cell carcinoma 4.3% 2.2% - - 0.8% 5.1%

 Adenocarcinoma, NOS§ 18.8% 16.0% 17.2% 14.4% 16.3% 16.7%

 Other specified carcinomas 3.6% 3.0% 5.2% 2.2% 1.9% 4.7%

 Unspecified carcinoma - 6.2% 8.6% 8.9% 11.1% 3.4%

Sex cord-stromal tumors 5.1% 0.5% 0.0% 6.1% 4.1% 1.3%

Germ-cell tumors 2.2% 3.1% 12.1% 7.2% 10.8% 3.0%

Unspecified cancer - 1.4% - 4.4% 0.8% 0.7%

Other specified types 2.9% 2.1% - 4.4% 3.5% 3.5%

*The symbols “-” = 1-2 cases; “[numeral]” (italics) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡The histologic types are included if they are higher than 1% in total in any of the MECC registries; percentages should sum over a column to 100% (with some rounding). However, where a 

percentage has been suppressed because it is based on only 1 or 2 cases, the remaining percentages may not sum to 100%.

§NOS indicates “not otherwise specified.”

The majority of ovarian cancer cases diagnosed in the age group 

50-69 years were in US SEER, Cypriots, and Israeli Jews. On 

the other hand, the majority of ovarian cancer cases diagnosed 

in women below the age of 50 were in Egyptians, Jordanians, 

and Israeli Arabs. Among women over 50 years, the incidence 

rate in US SEER, Cypriots, and Israeli Jews was, on average, 

approximately twice that in Egyptians, Jordanians, and Israeli 

Arabs. 

Among women younger than the age of 50, the incidence rate was 

between 2.1 and 3.2 in all populations under study, except in Israeli 

Arabs (1.4). This could imply a cohort effect, with women in newer 

generations of these populations having more similarities in their 

lifestyle. However, further observation is needed before drawing this 

conclusion. 
 MECC Monograph 95

Ovarian Cancer Chapter 10

REFERENCES

[1] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA 

Cancer J Clin 2005;55:74-108.

[2] Tortolero-Luna G, Mitchell MF. The epidemiology of ovarian cancer. J 

Cell Biochem Suppl 1995;23:200-7.

[3] Zhang M, Lee AH, Binns CW. Reproductive and dietary risk factors for 

epithelial ovarian cancer in China. Gynecol Oncol 2004;92:320-6.

[4] Daly M, Obrams GI. Epidemiology and risk assessment for ovarian cancer. Semin Oncol 1998;25:255-64.

[5] Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and 

prognostic factors. Semin Surg Oncol 2000;19:3-10.

[6] Engeland A, Tretli S, Bjorge T. Height, body mass index, and ovarian 

cancer: a follow-up of 1.1 million Norwegian women. J Natl Cancer Inst 

2003;95:1244-8.

[7] Riman T, Dickman PW, Nilsson S, Correia N, Nordlinder H, Magnusson 

CM, et al. Hormone replacement therapy and the risk of invasive epithelial ovarian cancer in Swedish women. J Natl Cancer Inst 2002;94:497-

504.

[8] Riman T, Persson I, Nilsson S. Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence. Clin Endocrinol (Oxf) 

1998;49:695-707.

[9] Souhami RL, Tannock I, Hohenberger P, Horiot JC, editors. Oxford 

textbook of oncology, second edition. Oxford (UK): Oxford University 

Press; 2001.

[10] Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in 

five continents, volume VIII. IARC Scientific Publication No. 155. Lyon 

(France): International Agency for Research on Cancer; 2002.
96 MECC Monograph 
 MECC Monograph 97

Urinary Bladder Cancer Chapter 11

AMAL SAMY IBRAHIM, HUSSEIN M. KHALED

BACKGROUND

Urinary bladder (or bladder) cancer is one of the most common 

cancers worldwide, with the highest incidence in industrialized 

countries. Age-standardized incidence rates (ASR) higher than 40 

per 100,000 for males were reported from Europe (Belgium, 42.5; 

Italy, 41.0). In most European countries, the United States, and 

Canada, rates are between 20 and 30. Bladder cancer incidence is 

lowest in Asia and South America, approximately 70% lower than in 

Western industrialized countries. 

As shown in Table 11.1, the lowest median bladder cancer ASR for 

males was in Asia (5.9), and the highest in Europe (23.9). Rates 

for females were much lower, but followed the same geographical 

pattern as for males. 

Marked variation in bladder cancer incidence occurs not only 

between but also within countries. Italy, which had one of the 

highest rates for males worldwide (41.1 in Genua province), also 

had a rate of 27.9 in Ragusa province. Nonetheless, because of its 

high recurrence rate, the actual prevalence of active bladder cancer 

is estimated to be about 10 times the number of new cases [1].

Histological Types

Two main histological types of bladder cancer are identified: the 

transitional cell carcinomas (TCC), related to cigarette smoking 

and most prevalent in Western and industrialized countries, and 

the squamous cell carcinomas (SCC), which are more frequently 

seen in some Middle Eastern and African countries, where urinary 

schistosomiasis is an endemic disease. Rare types of bladder cancer 

include small cell carcinoma, carcinosarcoma, primary lymphoma, 

and sarcoma [2]. 

In industrialized Western countries, transitional cell tumors comprise 

90%-95% of bladder tumors; 3%-7% are squamous cell, and 1%-

2% are adenocarcinomas. Transitional cell carcinomas may show 

evidence of squamous or adenocarcinomatous differentiation. Welldifferentiated tumors tend to recur, and the poorly differentiated 

tumors not only recur but also tend to invade locally and may 

metastasize [3].

In developing countries in certain locations, up to 75% of cases 

are squamous cell carcinomas associated with Schistosoma 

haematobium infestation. They most often form in the setting of a 

chronic inflammation, such as in patients with long-term catheters, 

or are the haematobium type of schistosomiasis and tend to be of 

high grade. These squamous cell carcinomas are highly malignant, 

with poor prognosis. Success in treating these cancers relies heavily 

on early detection and aggressive surgical management [4].

Etiology and Risk Factors

Cigarettes. Cigarette smoking, including exposure to secondhand 

smoke, is estimated to account for two-thirds of bladder cancers in 

males and one-third in females. There is strong correlation between 

the number of pack-years and the risk of developing bladder cancer. 

Quitting smoking decreases the risk, but the risk never returns to that of 

a nonsmoker. This situation is not unexpected, given the average 20-year 

latency between carcinogen exposure and bladder cancer development 

[5]. 

In the Middle East region, cigarette smoking could be considered 

a time bomb. According to the World Health Organization (WHO) 

statistics shown in Table 11.2, Middle East Cancer Consortium 

(MECC) countries had a higher percentage of male smokers in 

1998-1999, ranging from between 33.0% in Israel to 48.0% in 

Jordan, compared with 25.7% in the United States. Except for Israel 
98 MECC Monograph 

Urinary Bladder Cancer Chapter 11

Table 11.1. Bladder Cancer: Age-Standardized Incidence Rates* for the Highest, Median, and Lowest Country within Continent, by Sex − 

1993-1997†

Male Female

Continent Country Rate Country Rate

Africa

Highest France, La Reunion 12.0 Zimbabwe, Harare 8.3

Median Algeria 10.7 Algeria 2.3

Median Zimbabwe, Harare 8.3 France, La Reunion 1.3

Lowest The Gambia 1.3 The Gambia 0.5

South America

Highest Uruguay, Montevideo 22.6 Uruguay, Montevideo 4.3

Median United States, Puerto Rico 9.8 Brazil, Goiania 2.7

Lowest France, Martinique 3.6 Ecuador, Quito 1.3

North America

Highest United States, New Jersey, White 28.0 United States, Connecticut, White 8.0

Median United States, New Mexico, Non-Hispanic, White 19.4 United States, Louisiana, Central Region, White 5.2

Median United States, California, Los Angeles 19.0 United States, Louisiana, New Orleans 5.1

Lowest United States, New Mexico, American Indian 4.1 United States, New Mexico, American Indian 0.7

Asia

Highest Israel, Jews born in Europe or United States 27.8 Israel, Jews born in Europe or United States 6.0

Median China, Beijing 5.9 Singapore 1.7

Lowest India, Trivandrum 2.0 India, Karunagappally 0.3

Europe

Highest Belgium, Limburg 42.5 Scotland 8.1

Median England, South and Western Regions 23.9 Czech Republic 4.6

Median England, Merseyside and Cheshire 23.7 France, Doubs 4.5

Lowest Slovenia 11.1 Belarus 1.6

Australia

Highest United States, Hawaii, White 23.9 Australia, South 6.2

Median United States, Hawaii 13.4 United States, Hawaii, Japanese 3.4

Lowest United States, Hawaii, Hawaiian 6.8 United States, Hawaii, Filipino 2.2

Total World

Highest Belgium, Limburg 42.5 Zimbabwe, Harare 8.3

Median United States, Louisiana, Central Region 16.6 Spain, Navarra 3.9

Lowest The Gambia 1.3 India, Karunagappally 0.3

*Rates are per 100,000 and are age-standardized to the World Standard Million.

†Years vary slightly between countries.

Source: Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in five continents, volume VIII. IARC Scientific Publication No. 155. Lyon (France): International Agency for Research on Cancer; 2002.

(24.0%), the frequency of female smokers in MECC countries is 

generally low, opening a promising avenue for prevention. The 

number of cigarettes consumed in the MECC countries is still lower 

than in the United States, except for Israel, where annual cigarette 

consumption per person (2,162) is near US consumption (2,255) 

[6]. The bomb will explode due to long latency of the disease, 

increase in consumption, increase in female smokers, and exposure 

of more youth to the habit. 
 MECC Monograph 99

Urinary Bladder Cancer Chapter 11

Schistosomiasis. Schistosomiasis, also known as Bilharzias, is a 

parasitic disease caused by infection with schistosome blood flukes. 

Four schistosome species are parasitic in humans: S. haematobium, S. 

mansoni, S. Japonicum, and S. intercalatum. Of these, S. haematobium, 

also called urinary schistosomiasis, is the one related to bladder cancer. 

The disease is common in northeast Africa, southwest Asia, and 

Madagascar [7].

The S. Haematobium adult mature worms inhabit the mesenteric 

and pelvic veins of humans, where they mate and reproduce. 

The females deposit eggs that eventually rupture the venules and 

discharge into the surrounding tissues. Eggs are mainly carried to 

the bladder wall and excreted in urine. With their terminal spine, 

the eggs injure the bladder wall, leading to hematuria, calcification, 

and cystitis. When the excreted eggs reach fresh water, the miracidia 

hatch and infect water snails. Within the snails, mature sporocytes 

produce cercariae, which are expelled into the water, waiting for the 

human host. People who make contact with such water, mainly male 

farmers, get the disease. Children and adolescents are also at high 

risk, due to bathing and swimming in canals with infected snails [8].

Schistosomiasis is one of the oldest known parasitic diseases. 

Paleopathologic examination of mummified tissues detected 

schistosomal eggs in gastrointestinal and urinary tracts of mummies 

belonging to the 20th dynasty (1250-1200 BC) (Figure 11.1). 

Medical papyri show that ancient Egyptians knew not only the 

etiology of the disease and its main symptom (hematuria), but also 

recommended antimony as a line of treatment. Prevention was 

proposed through refraining from polluting water, and farmers and 

others with prolonged exposure to canal water were advised to wear 

penile sheaths to prevent the worms from entering their bodies. 

Furthermore, it was said that the deceased had to sign in the book 

of the dead that they had not polluted water during their lifetime 

[9,10]. 

The prevalence and severity of schistosomiasis tend to rise sharply 

with opportunities for exposure. In Egypt, the disease prevalence 

increased dramatically after installation of the High Dam, which 

created perennial irrigation. Thus, the peculiar agricultural 

setting of the Nile Valley singled out Egypt for a dose-response 

relationship not encountered in other parts of Africa [11]. Over 

the last 2 decades, Egypt succeeded in lowering the prevalence of 

schistosomiasis from 35% in 1983 to 1.7% in 2003, with complete 

eradication in certain districts [12] (Figure 11.2).

Table 11.2. Bladder Cancer: Adult and Youth Smoking Prevalence, Cigarettes Smoked, and Quit Rate in Cyprus, Israel 

(Jews and Arabs), Egypt, Jordan, and the United States − 1998-2000

Countries Population (in 

thousands)

Adult Smoking Prevalence Youth Smoking Prevalence Cigarettes 

Smoked Annually

 (per capita)

Quit Rate (among 

those who have 

ever smoked) Total Male Female Total Male Female

Cyprus 784 29.0% 38.5% 7.6% - - - - 11.0%

Israel 6,040 28.5% 33.0% 24.0% - - - 2,162 10.0%

Egypt 67,884 18.3% 35.0% 1.8% - - - 1,275 50.0%

Jordan 4,913 29.0% 48.0% 10.0% 20.6% 27.0% 13.4% 1,832 -

United States 283,230 23.6% 25.7% 21.5% 25.8% 27.5% 24.2% 2,255 42.0%

Source: Mackay J and Eriksen M. The tobacco atlas. Geneva (Switzerland): World Health Organization; 2002.
100 MECC Monograph 

Urinary Bladder Cancer Chapter 11

There is a plethora of literature incriminating S. haematobium

infestation as a risk factor for bladder cancer, but explanation for 

this association remains speculative [13]. Evidence that supports the 

association between schistosomiasis and bladder cancer includes the 

geographical correlation between the 2 conditions, the distinctive 

patterns of sex and age at diagnosis, the clinicopathological identity 

of schistosome-associated bladder cancer (SABC), and extensive 

evidence in experimentally infected animals [14]. Due to the 

previous lack of population-based registries in Egypt, data published 

so far have been mostly retrospective relative frequencies, with 

their inherent limitations. An age-standardized mortality rate for 

bladder cancer of 10.8 in males placed Egypt at the top of the list 

of the 54 countries that provided data for the 1987 WHO database, 

and supported the hypothesis that S. haematobium infection 

predisposes to malignant bladder neoplasms [15]. This populationbased study documents, for the first time, the effect of changes in 

schistosomiasis control on bladder cancer incidence.

Egyptian literature describes a special profile for SABC, with 

marked male predominance, relatively young age at diagnosis, 

predominance of squamous cell carcinoma (75% or more), severe 

urinary tract infection and calcification, and special predilection to 

farmers. The early onset of this type of bladder cancer might reflect 

the latent period of carcinogenesis that takes 20-30 years after 

the peak of schistosomal infestation in the third decade of life. In 

Egyptian hospital series, the mean age at diagnosis of SABC was 41 

years, about 5 years younger than patients with non-schistosomal 

bladder cancer, with a male-to-female ratio that ranged from 5:1 to 

9:1 [16].

Other risk factors. Certain organic chemicals – particularly aromatic 

(aryl)-amines such as naphthalene, benzidine, aniline dyes, and 4-

aminobiphenyl – are known bladder carcinogens and have helped 

identify high-risk occupations, including petroleum chemical/rubber 

workers, hairdressers, painters, textile workers, truck drivers, and 

aluminum electroplaters. Bladder cancer may also result from pelvic 

radiotherapy, phenacetin use, and cyclophosphamide exposure, resulting 

in a four- to five-fold relative risk increase, particularly when exposure is 

in a chronic low-dose form [17,18].

Age and sex are additional risk factors. Bladder cancer is 2 to 3 

times more common in males. People over the age of 70 years 

develop the disease 2 to 3 times more often than those aged 55-69 

years, and 15 to 20 times more often than those aged 30-54 years. 

The highest incidence occurs in males over age 60 years and females 

over age 70; however, even teenage males have a finite chance of 

bladder cancer, while it is very rare to see bladder cancer in a female 

under the age of 40 [19].

 Figure 11.1. Bladder Cancer: Egg of

S. Haematobium Found in Tissues of 

an Egyptian Mummy 

 Photograph used with permission from Prof. 

 Nabil El-Bolkainy, Professor of Pathology and Dean 

Emeritus, National Cancer Institute, Cairo University, 

Cairo, Egypt. 
 MECC Monograph 101

Urinary Bladder Cancer Chapter 11

A diet high in saturated fat and consumption of Aristolochia fangchi 

(an herb used in some weight-loss formulas) have been incriminated 

as risk factors for bladder cancer. There is also a strong racial/ethnic 

disparity, with disease much more common in Caucasians than in 

those of African, Latino, or Asian descent [20].

Genetic Background 

The major differences in the clinicopathologic features observed 

between the Western type of bladder cancer and SABC probably 

reflect underlying alternate tumor biology and carcinogenic 

pathways. 

Chromosomal studies. Several studies attempted to characterize the 

chromosomal aberrations of SABC, including both SCC and TCC 

subtypes. Data were compared with those of the Western world. Some 

studies revealed that deletions of chromosome 9p where a tumor 

suppressor gene (CDKN2) resides were more frequent in SCC (92%) 

than in TCC (39%). Allelic losses in chromosome 17p, where the p53

gene resides, were less frequent in SCC (38%) than TCC (60%) [21].

It was also demonstrated that the histopathologic subtype rather than 

the schistosomal impact itself determines the pattern of chromosomal 

changes. Aberrations of chromosomes 7, 9, and 17 showed reciprocal 

patterns in TCC and SCC, whether associated with schistosomiasis 

or not [22]. The predominantly male development of SABC has been 

explained by the high frequency of loss of chromosome Y. Using the 

0

5

10

15

20

25

30

35

40

1980 1985 1990 1995 2000 2005

Years

 Prevalence (%)

Figure 11.2. Bladder Cancer: Change in Prevalence of S. Haematobium in Egypt 

after Schistosomiasis Control Program – 1980-2003

Source: Department of Endemic Diseases, Ministry of Health and Population, Egypt (2004).
102 MECC Monograph 

Urinary Bladder Cancer Chapter 11

FISH technique, Khaled and Aly demonstrated that 41% of cases of 

SABC showed loss of chromosome Y [23].

Cancer genes. Oncogenes and tumor suppressor genes have been 

implicated in a variety of human cancers. Many studies have attempted 

to identify molecular events associated with specific genes that underlie 

neoplastic progression in the development of SABC. These include the 

inactivation of p53 [24,25], activation of H-ras [26], and inactivation 

of the retinoblastoma gene [27]. Studies indicate that Egyptian bladder 

cancers show p53 mutations in both the squamous and transitional types. 

These mutations are known to be related to lymph node metastasis and 

a greater propensity to progression, and in the Egyptian studies [24,25]

were associated with advanced stage of disease. Excess mutations might 

be due to high levels of urinary nitrates in bilharzial patients producing 

nitric oxide by inflammatory cells. In these cases, there is usually an 

overexpression of MDM2 as well. The ras oncogene does not seem to 

be strongly implicated in the differential process of carcinogenesis in 

SABC, judging from studies in different countries. An incidence of 10% 

of H-ras mutations was seen in bladder cancer in Japan and the United 

States, similar to the Egyptian cases. 

Habuchi et al. [28] suggested that cigarette smoking might have a 

significant impact on the mutations of the p53 gene in urothelial 

cancers. Urothelial carcinogenesis in the presence of schistosomiasis 

seems to proceed along pathways different from those linked to 

smoking, since cigarette smoking appears to have a significant 

impact on the mutation of the p53 gene with A:T to G:C transitions, 

which are not observed in SABC. 

RESULTS

As shown in Table 11.3, bladder cancer was one of the more 

common cancers in the MECC countries – especially Egypt, where 

it ranked first in males, representing 16.2% of male cancers. Among 

Egyptian females, its frequency was 4.0%, by far exceeded by breast 

cancer (37.6% of female malignancies). For both sexes together, the 

frequency of bladder cancer was 10.1%, nearly the same as nonHodgkin lymphoma (10.5%) and next in frequency to breast cancer 

(18.9%) (see Table 1.6).

Other MECC registries reported relative frequencies of bladder 

cancer in males of 12.3% for Cypriots, 10.0% for Israeli Jews, 

9.9% for Jordanians, and 8.1% for Israeli Arabs. The proportions in 

females were much lower, and bladder cancer was not among the 

10 most frequent types of cancer in females in these registries. For 

both sexes together, relative frequencies in other MECC countries 

were all lower than for Egypt, ranging from 7.5% down to 5.0%. 

The relative frequency in the United States was lower than in MECC 

countries for males, and similar to MECC countries for females 

(Table 11.3).

Among the MECC registries and US SEER, the male-to-female 

ratio for bladder cancer incidence was highest in Jordanians (7.4:1), 

followed by Israeli Arabs (6.9:1) and Cypriots (5.3:1). Ratios in 

Egyptians and Israeli Jews were very close to one another (4.2:1 and 

4.1:1, respectively). The US SEER ratio was the lowest (2.9:1). This 

male predominance could be attributed to cigarette smoking, which 

is more common among males than females. Nonetheless, previous 

reports from Egypt indicated a higher male-to-female ratio as one 

of the features of SABC. The lower ratio observed for Egypt in the 

current results favors the transition from SABC to the Western type, 

TCC, which is mostly related to cigarette smoking.

The relatively high frequency of bladder cancer in Egypt supports 

the etiological relationship to urinary schistosomiasis. Despite the 

marked decrease in prevalence of endemic schistosomiasis over the 

last 2 decades, Egypt is still paying the toll of the previously high 

prevalence of the disease. Comparison of the frequency of active 

urinary schistosomiasis previously reported during the era of high 

prevalence of the disease [8] and the age-specific incidence rate 

indicates a strong cohort effect (Figure 11.3). It could be anticipated 

that in the near future, there will be a marked decrease in SABC in 

Egypt as a sequel to schistosomiasis control. The potential risk is 
 MECC Monograph 103

Urinary Bladder Cancer Chapter 11

the rise in incidence of bladder cancer related to other risk factors, 

especially smoking. 

Overall Incidence 

Results, based for the first time on population data, show that Egypt 

had a serious problem of bladder cancer. The highest ASR for both 

sexes together was that of Egyptians (16.6), followed by Israeli 

Jews (15.1), Cypriots (11.2), and Israeli Arabs (8.6). Jordanians had 

0

10

20

30

40

50

60

70

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75

0

5

10

15

20

Bladder 

Cancer

Active 

Schistosomiasis

Age in Years

Figure 11.3. Bladder Cancer: Prevalence of of Active Schistosomiasis (AS) by 

Age and Age Distribution of Bladder Cancer (BC) in Egypt

Source: Data on prevalence of schistosomiasis from Khozam and El Ayayisha villages, Upper Egypt 1975. Higashi GI, 

Aboul-Enein MI. Diagnosis and epidemiology of schistosoma haematobium infections in Egypt. In: El-Bolkainy MN, 

Chu E editors. Detection of bladder cancer associated with schistosomiasis. Cairo (Egypt): Al-Ahram Press; 1992. 

p. 47-69. Data on age distribution of bladder cancer (1999-2001) from Table 11.5 in this chapter.

AS Prevalence (%) BC Relative Frequency (%)
104 MECC Monograph 

Urinary Bladder Cancer Chapter 11

Cyprus 

1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER†

1999-2001

Bladder cancer cases

Total 460 6,215 299 1,057 1,038 21,355

Male 387 4,991 261 852 915 15,893

Female 73 1,224 38 205 123 5,462

Bladder cancer as 

a proportion of all 

cancers

Total 7.5% 5.9% 5.0% 10.1% 5.7% 4.3%

Male 12.3% 10.0% 8.1% 16.2% 9.9% 6.2%

Female 2.4% 2.2% 1.4% 4.0% 1.4% 2.2%

Male-to-female ratio 5.3:1 4.1:1 6.9:1 4.2:1 7.4:1 2.9:1

Median age

Total 71.0 71.7 65.3 61.6 62.2 72.9

Male 70.7 71.3 65.2 61.8 62.3 72.5

Female 72.1 73.3 66.0 60.6 62.0 74.1

Age-standardized 

incidence rate‡

Total 11.2 15.1 8.6 16.6 7.6 12.2

Male 20.5 27.5 16.0 27.5 13.2 20.9

Female 3.3 5.1 2.1 6.3 1.8 5.5

Microscopically 

confirmed

Total 99.3% 94.5% 95.7% 88.7% 99.9% 98.7%

Male 99.2% 94.5% 96.2% 89.2% 100.0% 98.9%

Female 100.0% 94.3% 92.1% 86.8% 99.2% 98.2%

Table 11.3. Bladder Cancer: Summary Table of Cancer Statistics for Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 

1996-2001*

the lowest ASR (7.6), with less than half the rates of Egyptians and 

Israeli Jews. The US SEER rate was 12.2 (Table 11.3). 

Egyptians and Israeli Jews had the highest ASR for males (27.5), 

followed by Cypriots (20.5) and Israeli Arabs (16.0). Jordanians had 

the lowest rate (13.2). The SEER ASR was 20.9. For females, the 

same pattern was observed at a much lower level. Egyptians ranked 

first (6.3), followed very closely by Israeli Jews (5.1), then by 

Cypriots (3.3), Israeli Arabs (2.1), and Jordanians (1.8). The SEER 

ASR for females was 5.5. 

Comparison of male ASRs in Egypt with rates worldwide [29]

showed that Egypt occupied the 86th percentile, with rates surpassed 

only by those in some West European countries. The high rates 

in Israel could be attributed to smoking. Egypt is still paying the 

double toll of the increasing exposure to smoking and the effect of 

the previously high prevalence of schistosomiasis as an endemic 

disease, an effect that will possibly persist for 2 to 3 decades to 

come.

Age

As shown in Table 11.3, the median age of bladder cancer patients 

showed marked variation between countries, with a range of 11.3 

years, US SEER included. For both sexes, the youngest median 

age was that of Egyptians (61.6 years), followed by Jordanians 

(62.2 years) and Israeli Arabs (65.3 years). Median ages in 

Cypriots, Israeli Jews, and US SEER were all in the 70s. Median 

ages followed the same pattern for all registries, without too much 

difference between the sexes. This could be a reflection of the age 
 MECC Monograph 105

Urinary Bladder Cancer Chapter 11

Cyprus 

1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER†

1999-2001

Distribution of Microscopically Confirmed Cases

Histologic distribution§ 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Carcinoma

Total 99.6% 98.6% 98.3% 98.0% 99.6% 99.4%

Male 99.5% 98.5% 98.0% 98.4% 99.7% 99.5%

Female 100.0% 99.0% 100.0% 96.1% 99.2% 99.2%

Squamous cell 

carcinoma 

Total - 0.7% - 25.5% 1.8% 1.5%

Male - 0.7% 0.0% 21.7% 1.6% 100.0%

Female 0.0% 1.1% - 41.6% 3.3% 2.8%

Transitional cell 

carcinoma 

Total 96.5% 93.8% 92.0% 62.9% 90.8% 94.9%

Male 96.4% 94.0% 92.8% 67.1% 91.9% 95.6%

Female 97.3% 92.6% 85.7% 44.9% 82.8% 93.0%

Adenoca 

Total 1.3% 1.5% 3.5% 5.7% 3.8% 1.2%

Male 100.0% 1.4% 2.8% 5.0% 3.1% 1.1%

Female 2.7% 1.9% 8.6% 8.4% 9.0% 1.7%

Other specified 

carcinoma 

Total - 0.4% - - - 0.6%

Male - 0.4% - - - 0.6%

Female 0.0% 0.5% 0.0% 0.0% 0.0% 0.5%

Unspecified carcinoma 

Total 1.3% 2.2% 1.4% 3.8% 3.1% 1.2%

Male 1.6% 2.0% 1.6% 4.5% 3.0% 1.2%

Female 0.0% 2.8% 0.0% - 4.1% 1.2%

Sarcoma 

Total 0.0% 0.1% 0.0% 0.4% - 0.2%

Male 0.0% 0.1% 0.0% - - 0.1%

Female 0.0% - 0.0% 1.7% 0.0% 0.2%

Unspecified cancer 

Total 0.0% 0.1% 1.7% 1.5% 0.3% 0.2%

Male 0.0% 1.1% 2.0% 1.4% - 0.2%

Female 0.0% 0.5% 0.0% 1.7% - 0.3%

Other histologies 

Total - 0.3% 0.0% - 0.0% 0.2%

Male - 0.2% 0.0% 0.0% 0.0% 0.2%

Female 0.0% 0.3% 0.0% - 0.0% 0.3%

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Rates are per 100,000 and are age-standardized to the World Standard Million.

§Percentages should sum over a column to 100% (with some rounding). Where a percentage has been suppressed because it is based on only 1 or 2 cases, the remaining percentages will not sum to 100%.

Table 11.3. continued
106 MECC Monograph 

Urinary Bladder Cancer Chapter 11

structure of the populations studied. As described in the “Overview 

and Summary Data” chapter of this monograph, MECC countries 

showed 2 different age structures. Arab populations (Egyptians, 

Jordanians, and Israeli Arabs) were relatively young compared with 

Israeli Jews and Cypriots. This relatively low median age for Arab 

populations, with 50% younger than age 60 years, has serious public 

health implications due to productive years of life lost due to bladder 

cancer.

Table 11.4. Bladder Cancer: Number of Cases and Age Distribution, by 5-Year and Broader Age Groups and by Sex, in Cyprus, Israel (Jews 

and Arabs), Egypt, Jordan, and US SEER − 1996-2001* 

Cyprus

 1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs) 

1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER†

 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 460 387 73 6,215 4,991 1,224 229 261 38 1,057 852 205 1,038 915 123 21,355 15,893 5,462

5-Year Age Groups (Distribution)

00-04 y 0.0% 0.0% 0.0% - 0.0% - 0.0% 0.0% 0.0% - - 0.0% - - - 0.0% - 0.1%

05-09 y 0.0% 0.0% 0.0% - - 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% - - 0.0%

10-14 y 0.0% 0.0% 0.0% - 0.0% - 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% - -

15-19 y 0.0% 0.0% 0.0% 0.1% - - 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.4% 0.3% - 0.0% 0.0% -

20-24 y 0.7% - - 0.2% 0.2% 0.3% 0.0% 0.0% 0.0% - - 0.0% 0.6% 0.4% - 0.1% 0.1% 0.1%

25-29 y 0.9% 1.0% 0.0% 0.3% 0.2% 0.7% 1.3% 1.5% 0.0% - - - 1.0% 0.9% - 0.1% 0.1% 0.2%

30-34 y - - 0.0% 0.5% 0.5% 0.5% 2.0% 1.9% - 0.6% - 2.0% 1.6% 1.7% - 0.3% 0.3% 0.5%

35-39 y 0.9% - - 0.8% 0.8% 0.7% 2.0% 1.5% - 0.8% 0.9% 0.0% 2.9% 3.0% 2.4% 0.8% 0.8% 0.9%

40-44 y 1.7% 2.1% 0.0% 1.5% 1.6% 1.0% 4.3% 4.2% - 3.9% 3.5% 5.4% 3.9% 3.9% 4.1% 1.6% 1.7% 1.5%

45-49 y 3.7% 3.9% - 3.2% 3.2% 3.1% 6.4% 6.9% - 9.2% 8.6% 11.7% 6.5% 6.7% 4.9% 3.0% 3.1% 2.8%

50-54 y 5.9% 5.4% 8.2% 5.3% 5.5% 4.7% 7.4% 7.7% - 13.7% 13.5% 14.6% 11.4% 10.3% 19.5% 5.1% 5.1% 5.0%

55-59 y 8.0% 8.5% 5.5% 6.5% 6.8% 5.6% 10.0% 10.3% 7.9% 15.6% 16.1% 13.7% 14.2% 14.9% 8.9% 7.2% 7.5% 6.3%

60-64 y 8.9% 8.8% 9.6% 10.2% 11.0% 7.4% 15.4% 15.3% 15.8% 18.2% 18.7% 16.1% 16.6% 16.9% 13.8% 9.5% 9.9% 8.5%

65-69 y 15.2% 16.3% 9.6% 14.9% 15.3% 12.8% 17.1% 15.7% 26.3% 17.5% 17.4% 18.0% 16.3% 16.1% 17.9% 12.3% 12.6% 11.7%

70-74 y 19.3% 18.9% 21.9% 19.0% 18.9% 19.4% 11.4% 12.3% - 12.1% 12.6% 10.2% 12.3% 13.0% 7.3% 16.5% 17.0% 15.0%

75+ y 34.3% 33.9% 37.0% 37.4% 35.9% 43.5% 22.7% 22.6% 23.7% 8.1% 8.2% 7.8% 12.2% 11.8% 15.4% 43.3% 41.9% 47.4%

Broader Age Groups (Distribution)

Total cases 460 387 73 6,215 4,991 1,224 299 261 38 1,057 852 205 1,038 915 123 21,355 15,893 5,462

<40 y 2.8% 2.3% 5.5% 2.0% 1.8% 2.5% 5.4% 5.0% 7.9% 1.7% 1.5% 2.4% 6.6% 6.4% 8.1% 1.5% 1.3% 1.8%

40-59 y 19.3% 19.9% 16.4% 16.6% 17.1% 14.4% 28.1% 29.1% 21.1% 42.4% 41.7% 45.4% 35.9% 35.7% 37.4% 16.9% 17.3% 15.6%

60-69 y 24.1% 25.1% 19.2% 25.1% 26.3% 20.2% 32.4% 31.0% 42.1% 35.7% 36.0% 34.1% 32.9% 33.0% 31.7% 21.9% 22.5% 20.2%

70+ y 53.7% 52.7% 58.9% 56.4% 54.8% 62.9% 34.1% 34.9% 28.9% 20.2% 20.8% 18.0% 24.6% 24.8% 22.8% 59.8% 58.9% 62.4%

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
 MECC Monograph 107

Urinary Bladder Cancer Chapter 11

The age structure of bladder cancer patients in 5-year age groups 

is shown in Table 11.4. To avoid reporting incidence rates on small 

numbers of certain age groups, age was empirically grouped into 4 

categories: <40, 40-59, 60-69, and 70+ years. In Egypt and Jordan, 

the most frequent age group among bladder cancer patients was 

40-59 years (42.4% and 35.9% of total cases in the two countries, 

respectively), with decreasing frequency in successive age groups. 

The other registries reported a progressive increase in frequency to a 

peak in older age groups, although this trend was less marked among 

Israeli Arabs. 

Table 11.5 shows the age-specific incidence rates. It may be seen 

that rates in Egypt were highest in the age groups up to 70 years, but 

in those aged 70 years and older, incidence rates in Israel and the 

United States were higher than in Egypt. It is possible that this is 

due to underdiagnosis of elderly patients in Egypt, or it may point to 

a difference in the etiologies of SABC and tobacco-related bladder 

cancer.

Histology

Reports from all registries except Egypt showed a very low 

frequency of squamous cell carcinoma. In Egypt, SCC represented 

21.7% and 41.6% of male and female bladder cancers, respectively 

(Table 11.3). Previous reports from Egypt indicated a higher 

frequency of SCC that reached 75% of bladder malignancies. This 

lower frequency of SCC relative to previous reports supports the 

etiological relationship to urinary schistosomiasis in Egypt and the 

effect of successful control measures of the endemic disease. The 

increase in frequency of TCC and decrease in frequency of SCC 

relative to previous reports indicate a transition phase from the 

SABC to the Western type of bladder cancer related to smoking. 

For TCC, the ASR for both sexes together showed marked variation 

between registries (Table 11.6). The highest rate was that of Israeli 

Jews (13.5), almost double the lowest rate (Jordanians, 6.9). Next to 

Israeli Jews were Cypriots (10.7), Egyptians (9.3), and Israeli Arabs 

(7.6). The US SEER rate was 11.5. 

The same ranking of TCC incidence rates was observed for males 

and females. The highest rates were those of Israeli Jews (24.6 and 

4.5), followed by Cypriots (19.5 and 3.2), Egyptians (16.4 and 2.4), 

Israeli Arabs (14.3 and 1.7), and Jordanians (12.1 and 1.5), for males 

and females, respectively – another point underlining the serious 

effects of the uncontrolled smoking epidemic. The corresponding 

US SEER rates were 19.8 for males and 5.0 for females. For all 

registries, rates showed progressive increases with aging. 

Comparison of incidence rates of SCC was possible for Egypt and 

US SEER only, due to small numbers and very low rates in other 

registries (Table 11.6). ASRs for Egypt, both sexes, were almost 12-

25 times the rates of US SEER, which were the same for males and 

females. US SEER rates showed a progressive increase with age. In 

Egypt, rates increased to a much higher peak that occurred among 

the age group 60-69 years (21.0, 31.6, and 10.8, for both sexes, 

males, and females, respectively). This observation supports the 

relationship between bladder cancer and schistosomiasis. The TCC 

to SCC ratio that was reversed relative to previous reports indicates 

that Egypt is in a transition phase between SABC and the Western 

cigarette-related type of bladder cancer. 

SUMMARY AND CONCLUSIONS 

Bladder cancer is one of the more common cancers in the Middle 

East countries under study. Egypt had both the highest frequency 

and incidence rates and had a different histological pattern than 

other countries. This could be attributed to the relationship between 

bladder cancer and S. haematobium, a parasitic disease that used 

to be endemic in Egypt, and which is currently under control, with 

complete eradication in certain districts. In the present study, this 

relationship was supported for the first time by population-based 

data. Egypt was the only country that showed a high frequency 

and incidence of squamous cell carcinoma, which is the histologic 

type related to schistosomiasis. Egypt also showed an earlier peak 

of age-specific incidence rates, possibly due to the early age at 

schistosomal infection and the latent time needed for carcinogenesis. 
108 MECC Monograph 

Urinary Bladder Cancer Chapter 11

Table 11.5. Bladder Cancer: Age-Specific Incidence Rates,* by 5-Year and Broader Age Groups and by Sex, in Cyprus, Israel (Jews and 

Arabs), Egypt, Jordan, and US SEER − 1996-2001†

Cyprus

 1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER‡

 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

5-Year Age Groups (Rates)

Total Rate 11.2 20.5 3.3 15.1 27.5 5.1 8.6 16.0 2.1 16.6 27.5 6.3 7.6 13.2 1.8 12.2 20.9 5.5

00-04 y 0.0 0.0 0.0 - 0.0 - 0.0 0.0 0.0 - - 0.0 - - - 0.1 - 0.1

05-09 y 0.0 0.0 0.0 - - 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 - - 0.0

10-14 y 0.0 0.0 0.0 - 0.0 - 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 - -

15-19 y 0.0 0.0 0.0 0.2 - - 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.2 - 0.1 0.1 -

20-24 y 1.5 - - 0.5 0.7 0.3 0.0 0.0 0.0 - - 0.0 0.2 0.2 - 0.2 0.4 0.1

25-29 y 2.1 4.3 0.0 0.9 1.0 0.7 0.7 1.3 0.0 - - - 0.4 0.6 - 0.4 0.4 0.3

30-34 y - - 0.0 1.8 3.0 0.6 1.2 1.9 - 0.8 - 1.1 0.9 1.5 - 0.8 0.9 0.6

35-39 y 1.9 - - 2.7 4.6 1.0 1.4 1.8 - 1.1 2.3 0.0 2.1 3.7 0.4 1.8 2.6 1.0

40-44 y 3.9 7.9 0.0 5.0 9.0 1.3 4.0 6.7 - 6.9 9.9 3.7 3.9 6.8 1.0 3.7 5.7 1.8

45-49 y 9.4 16.8 - 10.5 17.6 3.9 7.7 14.7 - 19.3 27.5 10.1 7.7 13.9 1.4 7.7 11.9 3.6

50-54 y 16.4 25.8 7.2 21.8 37.3 7.2 11.5 21.0 - 40.1 64.0 16.5 15.2 23.4 6.4 15.0 22.9 7.4

55-59 y 26.5 47.8 5.6 38.4 67.3 12.4 19.3 34.4 3.9 61.2 98.9 21.3 21.7 38.4 3.4 28.6 45.5 12.5

60-64 y 35.3 60.4 11.7 59.6 111.2 15.6 38.9 70.7 9.7 76.5 133.4 25.1 34.4 58.4 7.2 49.8 80.6 21.7

65-69 y 70.8 138.2 13.1 94.4 176.0 28.9 59.2 105.9 21.1 106.4 169.7 42.7 50.5 81.7 14.2 76.2 125.6 34.1

70-74 y 107.7 197.8 35.0 130.5 243.7 46.0 58.0 128.5 - 109.7 194.2 34.1 57.7 110.8 7.9 110.0 192.0 45.7

75+ y 119.1 229.4 35.7 162.4 303.9 63.2 92.1 171.5 22.8 100.1 175.9 34.7 50.5 92.0 14.2 148.0 286.3 65.4

Broader Age Groups (Rates)

Total Rate 11.2 20.5 3.3 15.1 27.5 5.1 8.6 16.0 2.1 16.6 27.5 6.3 7.6 13.2 1.8 12.2 20.9 5.5

<40 y 0.7 1.0 0.4 0.6 0.9 0.3 0.3 0.5 0.1 0.2 0.3 0.1 0.4 0.6 0.1 0.3 0.4 0.2

40-59 y 12.8 22.3 3.4 16.9 29.3 5.6 9.7 17.7 1.8 28.7 44.8 12.0 11.1 18.8 2.8 12.3 19.2 5.7

60-69 y 50.5 93.7 12.3 74.5 139.0 21.3 47.6 85.8 14.6 89.3 149.0 32.6 41.3 68.4 10.2 61.1 99.9 27.0

70+ y 113.4 213.6 35.4 146.4 273.8 54.6 75.1 150.0 14.4 104.9 185.1 34.4 54.1 101.4 11.0 129.0 239.1 55.5

*Rates are per 100,000, and for the broad age groups are age-standardized to the World Standard Million.

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

Nevertheless, the profile of bladder cancer in Egypt was not 

typical of that described in earlier reports about the disease. Male 

predominance was marked but was not specific for Egypt. The 

frequency of squamous cell carcinoma, though relatively high, was 

lower than that usually seen with schistosomal-associated bladder 

cancer. The profile seemed to be one of a transition toward tobaccorelated bladder cancer, possibly due to decreasing prevalence of 

schistosomiasis during the last 2 decades. 
 MECC Monograph 109

Urinary Bladder Cancer Chapter 11

Other risk factors, mainly smoking, are responsible for the high 

incidence of bladder cancer in other countries in the region. The 

economic burden of the disease is greater in Arab populations, 

particularly Egypt, where the median age of diagnosis is younger 

than in the West. Efforts toward smoking control and respecting 

the rights of nonsmokers must be intensified. Smoking rates appear 

to be higher in the Middle East region than in the United States, 

although the amount of cigarettes smoked in the Middle East may be 

lower. 

A prospective study could be of value to document the change in the 

bladder cancer profile in Egypt during the current post-schistosomal 

control era, with transition from schistosome-related SCC to the 

smoking-related TCC common in Western countries. 

REFERENCES

[1] Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al. 

Radical cystectomy in the treatment of invasive bladder cancer: long-term 

results in 1,054 patients. J Clin Oncol 2001;19:666-75.

[2] Sengupta N, Siddiqui E, Mumtaz FH. Cancers of the bladder. J R Soc 

Health 2004;124:228-9.

[3] Messing EM, Young TB, Hunt VB, Gilchrist KW, Newton MA, Bram LL, 

et al. Comparison of bladder cancer outcome in men undergoing hematuria home screening versus those with standard clinical presentations. 

Urology 1995;45:387-96.

[4] El Sebaie M, Zaghloul MS, Howard G, Mokhtar A. Squamous cell 

carcinoma of the bilharzial and non-bilharzial urinary bladder: a review 

of etiological features, natural history, and management. Int J Clin Oncol 

2005;10:20-5.

Table 11.6. Bladder Cancer: Age-Standardized Incidence Rates,* by Histological Type and Sex, in Cyprus, Israel (Jews and Arabs), 

Egypt, Jordan, and US SEER − 1996-2001†

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER‡

1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Transitional Cell Carcinoma

Total rate 10.7 19.5 3.2 13.5 24.6 4.5 7.6 14.3 1.7 9.3 16.4 2.4 6.9 12.1 1.5 11.5 19.8 5.0

<40 y 0.6 1.0 0.3 0.5 0.8 0.2 0.3 0.5 0.1 0.1 0.2 - 0.3 0.5 0.1 0.3 0.4 0.2

40-59 y 12.8 22.3 3.4 15.5 26.8 5.0 8.6 16.1 1.2 15.9 26.8 4.5 10.0 17.2 2.3 11.6 18.3 5.2

60-69 y 46.3 85.0 12.3 67.7 126.4 19.3 42.7 77.3 12.7 50.3 88.7 13.8 38.1 63.9 8.5 58.1 95.5 25.3

70+ y 109.3 205.2 34.7 127.9 239.1 47.6 63.9 130.0 10.6 58.2 110.7 11.9 48.9 92.5 9.2 120.6 224.9 50.9

Squamous Cell Carcinoma

Total rate 3.7 5.1 2.3 0.2 0.2 0.1

<40 y 0.1 0.1 - 0.0 - 0.0

40-59 y 7.5 10.2 4.7 0.2 0.2 0.2

60-69 y 21.0 31.6 10.8 0.7 0.8 0.6

70+ y 14.3 16.8 12.2 1.9 2.6 1.4

*Rates are per 100,000, and rates for the broad age groups are age-standardized to the World Standard Million.

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
 110 MECC Monograph 

Urinary Bladder Cancer Chapter 11

[5] Peterson RO, editor. Urologic pathology, second edition. Philadelphia (PA): 

J.B. Lippincott; 1992.

[6] Mackay J and Eriksen M. The tobacco atlas. Geneva (Switzerland): World 

Health Organization; 2002.

[7] Vaishnav VP. Schistosomiasis induced squamous cell carcinoma of the 

urinary bladder. Indian J Pathol Microbiol 2003;46:148-9.

[8] Higashi GI, Aboul-Enein MI. Diagnosis and epidemiology of schistosoma 

haematobium infections in Egypt. In: El-Bolkainy MN, Chu E, editors. 

Detection of bladder cancer associated with schistosomiasis. Cairo (Egypt): 

Al-Ahram Press; 1992. p. 47-69.

[9] Badr MM. The history of urology in ancient Egypt. J Int Coll Surg 

1963;39:404-13.

[10] Badr MM. Schistosomiasis in ancient Eqypt. In: El-Bolkainy MN, Chu E, 

editors. Detection of bladder cancer associated with schistosomiasis. Cairo 

(Egypt): Al-Ahram Press; 1992. p. 124-8.

[11] Mostafa MH, Sheweita SA, O’Connor PJ. Relationship between schistosomiasis and bladder cancer. Clin Microbiol Rev 1999;12:97-111.

[12] Ministry of Health and Population. Prevalence of schistosomiasis on Egypt. 

Report of the Department of Endemic Disease (personal communication). 

(Egypt): Ministry of Health and Population; 2002.

[13] Cheever AW. Schistosomiasis and neoplasia. J Natl Cancer Inst 

1978;61:13-8.

[14] Badawi AF, Mostafa MH, Probert A, O’Connor PJ. Role of schistosomiasis 

in human bladder cancer: evidence of association, aetiological factors, and 

basic mechanisms of carcinogenesis. Eur J Cancer Prev 1995;4:45-59.

[15] World Health Organization. Evaluation of carcinogenic risk to humans: 

schistosomes, liver flukes and Helicobactor pylori. IARC Monograph 

1994;61:45-119.

[16] Shokeir AA. Squamous cell carcinoma of the bladder: pathology, diagnosis 

and treatment. BJU Int 2004;93:216-20.

[17] Gordon O, Carel RS, Kordish E. The role of occupational exposures in the 

etiology of bladder cancer [Hebrew]. Harefuah 2004;143:772-4, 840.

[18] Travis LB, Curtis RE, Glimelius B, Holowaty EJ, van Leeuwen FE, Lynch 

CF, et al. Bladder and kidney cancer following cyclophosphamide therapy 

for non-Hodgkin’s lymphoma. J Natl Cancer Inst 1995;87:524-30.

[19] Cohen SM, Shirai T, Steineck G. Epidemiology and etiology of premalignant 

and malignant urothelial changes. Scand J Urol Nephrol Suppl 2000;105-15.

[20] Negri E, La Vecchia C. Epidemiology and prevention of bladder cancer. Eur 

J Cancer Prev 2001;10:7-14.

[21] Gonzalez-Zulueta M, Shibata A, Ohneseit PF, Spruck CH, III, Busch C, 

Shamaa M, et al. High frequency of chromosome 9p allelic loss and CDKN2 

tumor suppressor gene alterations in squamous cell carcinoma of the bladder. 

J Natl Cancer Inst 1995;87:1383-93.

[22] Pycha A, Mian C, Posch B, Haitel A, El Baz M, Ghoneim MA, et al. 

Numerical aberrations of chromosomes 7, 9 and 17 in squamous cell and 

transitional cell cancer of the bladder: a comparative study performed by 

fluorescence in situ hybridization. J Urol 1998;160:737-40.

[23] Khaled HM, Aly MS, Magrath IT. Loss of Y chromosome in bilharzial bladder cancer. Cancer Genet Cytogenet 2000;117:32-6.

[24] Weintraub M, Khaled HM, Abdel-Rahman Z, Bahnasi A, Eissa S, Venzon DJ, et al. p53 mutations in Egyptian bladder cancer. Int J Oncol 

1995;7:1269-74.

[25] Osman I, Scher HI, Zhang ZF, Pellicer I, Hamza R, Eissa S, et al. Alterations 

affecting the p53 control pathway in bilharzial-related bladder cancer. Clin 

Cancer Res 1997;3:531-6.

[26] Fujita J, Nakayama H, Onoue H, Rhim JS, el Bolkainy MN, el Aaser AA, et 

al. Frequency of active ras oncogenes in human bladder cancers associated 

with schistosomiasis. Jpn J Cancer Res 1987;78:915-20.

[27] El-Mawla NG, El-Bolkainy MN, Khaled HM. Bladder cancer in Africa: 

update. Semin Oncol 2001;28:174-8.

[28] Habuchi T, Takahashi R, Yamada H, Ogawa O, Kakehi Y, Ogura K, et al. 

Influence of cigarette smoking and schistosomiasis on p53 gene mutation in 

urothelial cancer. Cancer Res 1993;53:3795-9.

[29] Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in 

five continents, volume VIII. IARC Scientific Publication No. 155. Lyon 

(France): International Agency for Research on Cancer; 2002.
 MECC Monograph 111

Brain and Other Central Nervous System Cancer Chapter 12

PETER D. INSKIP, ELAINE RON

BACKGROUND

Brain and other central nervous system (CNS) cancers include a 

variety of histopathologic subtypes, but the most common, by far, 

are gliomas. These tumors, which arise from the glial cells that 

surround and support neurons, include astrocytoma, glioblastoma, 

oligodendroglioma, oligoastrocytoma, and ependymoma. 

Medulloblastoma, another neuroepithelial cancer, is relatively 

common in children but rare in adults. Brain cancers in children 

typically arise in the cerebellum, whereas brain cancers in adults are 

more likely to occur in the cerebral hemispheres [1]. In adults, older 

age at diagnosis of brain cancer is associated with higher tumor 

grade and poorer prognosis. Indeed, glioblastoma is among the 

most lethal of all cancers. Molecular studies of brain cancers reveal 

still greater heterogeneity of tumor types than is apparent based on 

histopathology, and efforts are underway to develop a molecular 

classification of brain cancer.

Very little is known about the etiology of brain and other CNS 

cancers [2-4]. These cancers occur in association with several rare 

familial cancer syndromes, such as neurofibromatosis type 1 and 

Li-Fraumeni syndrome [5-8], but genetic predisposition related to 

such syndromes is unlikely to account for more than a few percent 

of brain cancers [9]. The only clearly established environmental risk 

factor is ionizing radiation, particularly for exposures to therapeutic 

doses during childhood [10-15]. Risks related to modern diagnostic 

radiography probably are very small. Unlike ionizing radiation, there 

is little evidence that non-ionizing radiation from electric power 

lines, appliances, or cellular telephones causes brain or other CNS 

cancers [16,17].

Recorded brain cancer incidence rates increased over the past 

several decades in most developed countries, particularly in the 

elderly, but this is generally thought to be due more to improved 

diagnosis than to a real increase in incidence [18,19]. Incidence of 

glioma is positively associated with socioeconomic status [20,21]. 

In the United States, incidence is highest in Whites, intermediate for 

Blacks, and lowest for Asians; however, incidence rates for brain 

cancer exhibit less international variation than do most cancers, 

particularly when probable differences in completeness of diagnosis 

are taken into account [2,22]. Cancer of the brain and other CNS 

is more common in males than females [23]. A possible role of 

steroid sex hormones has been hypothesized, and a recent report 

noted reduced risk of glioma associated with early age at menarche 

and early age at first live birth [24]. Several studies have indicated 

a reduced risk of glioma among persons with a history of allergies 

or certain infections, possibly indicating a role for immune factors 

[25-30]. A recent report noted an inverse association between use of 

nonsteroidal anti-inflammatory drugs and glioblastoma [31].

The blood-brain barrier is effective at keeping many potentially 

toxic agents in the bloodstream from reaching the glial cells that 

give rise to most brain cancers [32]. In studies with experimental 

animals, the most potent known chemical neurocarcinogens are 

nitrosamides, such as nitrosoureas, which can cross the bloodbrain barrier [33-36]. Such compounds can be formed in the 

stomach from nitrites and amides in the diet. Whether they are 

important carcinogens in humans is an unresolved issue [2,37,38]. 

Experimental studies indicate that the developing nervous system is 

more susceptible to carcinogens than is the mature nervous system 

[33,34,36]. The suggestion of a higher radiation-related brain 

cancer risk for children compared with adults is consistent with this 

observation [14,15].
 112 MECC Monograph 

Brain and Other Central Nervous System Cancer Chapter 12

RESULTS

Overall Incidence

The number of brain and other CNS cancers available for analysis 

in the Middle East Cancer Consortium (MECC) ranged from a low 

of 150 in Cypriots to a high of 1,690 in Israeli Jews (Table 12.1). 

Brain and other CNS cancers accounted for 4.8% of all cancers 

in Jordanians, 3.4% in Israeli Arabs, 3.1% in Egyptians, 2.4% in 

Cypriots, 1.6% in Israeli Jews, and 1.4% in US SEER (see Table 

1.6). In each country, a large majority of cancers were located in the 

brain, but the proportion varied from 85.2% in Egyptians to 94.5% 

in Israeli Arabs. The rank order in age-standardized incidence rates 

(ASRs) for brain/CNS cancer for males and females combined 

was, in descending order, Israeli Jews, Cypriots, Jordanians, Israeli 

Arabs, and Egyptians. US SEER rates were similar to those for 

Israeli Jews (Table 12.1). The high incidence of brain and other 

CNS cancers in Israeli Jews is of note because an earlier analysis of 

data from the Israel Cancer Registry found a statistically significant 

increase in meningioma incidence rates among Israeli Jews born 

in either North Africa or the Middle East between 1940 and 1954. 

This observation is thought to be related to the considerable number 

of individuals in these 2 cohorts who received radiation therapy as 

children for treatment of tinea capitis [39]. While incidence rates 

for malignant brain tumors also increased among persons irradiated 

for tinea capitis, the risks were substantially smaller, and therefore 

the radiation exposure may not be a contributing factor in the high 

incidence of malignant brain tumors in Israeli Jews seen in Table 

12.1. 

The ASR for brain cancer was higher in males than females for each 

country, but the male-female incidence rate ratio varied from 1.08 

in Cypriots and 1.10 in Egyptians to a high of 1.64 in Israeli Arabs. 

The rates of other CNS cancer were similar between sexes in most 

countries. Figure 12.1 extends the comparison of incidence rates to 

other countries in the region and worldwide. ASRs in the MECC 

countries were lower than those in the United States (Whites), 

northern Europe, and Australia, but higher than in Asia. Kuwait 

showed rates intermediate to those of MECC countries, whereas 

rates were decidedly lower in Oman, but this may be partly due to 

some under-ascertainment of cases [23]. Incidence among Blacks 

in the United States was more similar to that of populations in Arab 

countries than it was to Whites in the United States. The ranking of 

the countries by incidence in females is similar, but not identical, to 

that based on males.

Basis of Diagnosis

As shown in Table 12.2, the proportion of brain and other CNS 

cancers with microscopic confirmation was 94.7% in Jordanians, 

87.5% in US SEER, 83.0% in Israeli Arabs, 80.0% in Cypriots, 

79.1% in Israeli Jews, and 65.7% in Egyptians. In Cypriots, the 

proportion was higher in females than in males, whereas the reverse 

was true for the other populations (data not shown).

Subsites 

Among brain cancers, the proportion coded to “Brain, not otherwise 

specified (NOS)” was far higher in the MECC countries than in the 

United States. This is reflected in the percentages in the category 

“Other/Unspecified” (shown in Table 12.1), which mostly consists 

of those cancers coded to “Brain, NOS.” Whether this is related to 

the quality of medical records, less frequent use of MRI and CT, 

tumor registration practices, or other factors is unclear. Although 

the percentage of microscopically confirmed brain cancers was 

lower in Cypriots, Israeli Jews and Arabs, and Egyptians than in US 

SEER, this is not correlated with the proportion of brain cancers 

with unspecified location. MECC data showed that in Jordan, 94.7% 

of the brain cancers were microscopically confirmed, but 52% had 

unspecified location; in Egypt, although as few as 65.7% of the brain 

cancers were microscopically confirmed, only 33% had unspecified 

location. (Note that the percentage of the “Other/Unspecified” 

category shown in Table 12.1 is just over 50% for both Jordan and 

Egypt. However, whereas for Jordan almost all of this category 
 MECC Monograph 113

Brain and Other Central Nervous System Cancer Chapter 12

Table 12.1. Brain and Other Central Nervous System (CNS) Cancer: Number of Cases, Site Distribution, and Age-Standardized Incidence Rates, by Subsite 

and Sex, in Cyprus, Israel (Jews and Arabs), Egypt, and Jordan − 1996-2001*

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 150 79 71 1,690 939 751 200 122 78 324 165 159 875 506 369 7,060 3,964 3,096

Primary Site (Distribution)

Brain/Other CNS combined‡ 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

 Brain 87.3% 86.1% 88.7% 94.4% 95.4% 93.2% 94.5% 95.1% 93.6% 85.2% 86.1% 84.3% 92.3% 93.1% 91.3% 93.6% 94.9% 92.1%

 Other CNS 12.7% 13.9% 11.3% 5.6% 4.6% 6.8% 5.5% 4.9% 6.4% 14.8% 13.9% 15.7% 7.7% 6.9% 8.7% 6.4% 5.1% 7.9%

Detailed Primary Site (Distribution)

Brain/Other CNS combined‡ 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

 Cerebrum 34.0% 34.2% 33.8% 39.9% 40.4% 39.4% 29.0% 27.9% 30.8% 19.8% 21.2% 18.2% 24.0% 23.7% 24.4% 55.9% 57.8% 53.6%

 Cerebellum 4.7% 6.3% - 3.1% 3.4% 2.8% 7.0% 6.6% 7.7% 11.4% 11.5% 11.3% 12.2% 13.4% 10.6% 6.0% 6.4% 5.5%

 Ventricles 0.0% 0.0% 0.0% 2.6% 2.7% 2.5% 4.0% 5.7% - 0.9% - - 1.9% 1.6% 2.4% 2.1% 2.1% 2.0%

 Brain stem 2.0% 0.0% 4.2% 2.5% 2.8% 2.1% 5.0% 6.6% - 4.0% 3.6% 4.4% 3.1% 2.8% 3.5% 4.2% 3.7% 4.9%

 Meninges 2.0% - - 2.4% 2.0% 2.9% 2.0% - - - 0.0% - 2.2% 2.6% 1.6% 1.8% 1.1% 2.6%

 Spinal cord 8.0% 7.6% 8.5% 1.7% 1.8% 1.5% 1.5% - - 4.0% 3.6% 4.4% 2.4% 1.8% 3.3% 2.9% 2.5% 3.4%

 Cranial nerves - - 0.0% 0.7% - 1.2% 0.0% 0.0% 0.0% - - - 0.5% - 0.8% 0.9% 0.9% 1.0%

 Other/Unspecified 48.0% 48.1% 47.9% 47.1% 46.8% 47.5% 51.5% 50.8% 52.6% 58.6% 58.8% 58.5% 53.7% 54.0% 53.4% 26.2% 25.6% 27.0%

Detailed Primary Site (Rates)§

Brain/Other CNS combined 4.9 5.2 4.6 5.2 6.1 4.3 3.9 4.8 3.0 3.7 3.8 3.5 4.0 4.4 3.6 5.2 6.2 4.4

 Brain 4.1 4.3 4.0 4.9 5.8 4.0 3.6 4.6 2.8 3.2 3.3 3.0 3.7 4.1 3.3 4.9 5.8 4.0

 Other CNS 0.8 0.9 0.6 0.3 0.3 0.3 0.2 0.2 0.2 0.5 0.5 0.5 0.3 0.3 0.3 0.4 0.3 0.4

Cerebrum 1.5 1.6 1.4 2.0 2.4 1.7 1.3 1.6 0.9 0.8 0.8 0.7 1.2 1.3 1.0 2.8 3.4 2.2

Cerebellum 0.3 0.4 - 0.2 0.2 0.2 0.2 0.2 0.1 0.3 0.3 0.3 0.3 0.4 0.3 0.4 0.5 0.4

Ventricles 0.0 0.0 0.0 0.2 0.2 0.1 0.1 0.2 - 0.0 - - 0.1 0.1 0.1 0.1 0.2 0.1

Brain stem 0.1 0.0 0.3 0.2 0.2 0.1 0.1 0.2 - 0.1 0.1 0.1 0.1 0.1 0.1 0.3 0.3 0.3

Meninges 0.1 - - 0.1 0.1 0.1 0.1 - - - 0.0 - 0.1 0.1 0.1 0.1 0.1 0.1

Spinal cord 0.5 0.5 0.5 0.1 0.1 0.1 0.1 - - 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2

Cranial nerves - - 0.0 0.0 - 0.1 0.0 0.0 0.0 - - - 0.0 - 0.0 0.1 0.1 0.1

Other/Unspecified 2.3 2.5 2.1 2.4 2.8 2.0 2.1 2.5 1.7 2.3 2.4 2.2 2.2 2.4 1.9 1.3 1.5 1.0

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Percentages should sum over a column to 100% (with some rounding). However, where a percentage has been suppressed because it is based on only 1 or 2 cases, the remaining percentages will not sum to 100%.

§Rates are per 100,000 and are age-standardized to the World Standard Million.
 114 MECC Monograph 

Brain and Other Central Nervous System Cancer Chapter 12

US SEER (Whites)

 Australia: NSW

 Sweden

 Scotland

Israel (Jews)

 Czech Republic

Cyprus

Israel (Arabs)

Jordan

Kuwait

US SEER (Blacks)

Eygpt

 India: Bombay

 Singapore

Oman

 Japan: Hiroshima

7 6 5 4 3 2 1 0 1 2 3 4 5 6 7 0

Male

Female

Figure 12.1. Brain and Central Nervous System Cancer: Age-Standardized Incidence

Rates* by Country

Age-Standardized Incidence Rate per 100,000

*Rates are per 100,000 and are age-standardized to the World Standard Million.

Sources: Data for non-MECC populations are taken from: Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in five continents, volume VIII. IARC

Scientific Publication No. 155. Lyon (France): International Agency for Research on Cancer; 2002. Data for MECC populations are taken from the MECC database.
 MECC Monograph 115

Brain and Other Central Nervous System Cancer Chapter 12

consisted of tumors of unspecified location, for Egypt about 40% 

of this category consisted of “overlapping lesions,” the remaining 

having unspecified location.) The ratio of the number of tumors 

occurring in the cerebellum to the number occurring in the cerebrum 

was higher in Egypt and Jordan than in the other countries. This 

reflects the young age structures of populations in these countries 

(see Figure 1.1) and the tendency of pediatric brain cancers to occur 

in the cerebellum. Comparison of subsite-specific incidence rates 

must be made with caution in light of the variable proportions with 

unspecified location.

Age

Age-specific incidence rates in the different countries were quite 

similar through middle age, with the major differences emerging 

at older ages (Figure 12.2). Small peaks in incidence rates were 

apparent for young children in some, but not all, MECC countries. 

Rates typically were lowest in the second or third decade of life and 

increased markedly beginning in the 40s or early 50s. A leveling 

off or decrease in incidence at the oldest ages was seen in most 

countries. This might reflect differences in the completeness of 

diagnosis. The age distribution of cases varied dramatically among 

Table 12.2. Brain and Other Central Nervous System Cancer: Number of Cases Microscopically Confirmed and Proportions of Microscopic Confirmation, by 

Histology and Sex, in Cyprus, Israel (Jews and Arabs), Egypt, and Jordan − 1996-2001*

Cyprus

1998-2001

Israel (Jews)

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases microscopically confirmed 120 61 59 1,337 759 578 166 105 61 213 109 104 829 485 344 6,175 3,556 2,619

Microscopically confirmed 80.0% 77.2% 83.1% 79.1% 80.8% 77.0% 83.0% 86.1% 78.2% 65.7% 66.1% 65.4% 94.7% 95.9% 93.2% 87.5% 89.7% 84.6%

Distribution of Microscopically Confirmed Cases

Histologic distribution‡ 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Tumours of neuroepithelial tissue 93.3% 91.8% 94.9% 93.6% 94.3% 92.7% 93.4% 91.4% 96.7% 94.4% 94.5% 94.2% 91.0% 91.3% 90.4% 95.5% 96.3% 94.5%

 Gliomas 87.5% 86.9% 88.1% 87.7% 87.9% 87.5% 81.9% 80.0% 85.2% 81.7% 83.5% 79.8% 76.1% 74.0% 79.1% 90.3% 90.7% 89.8%

 Astrocytic tumours 76.7% 78.7% 74.6% 70.7% 69.8% 71.8% 63.3% 63.8% 62.3% 67.6% 70.6% 64.4% 60.3% 59.6% 61.3% 69.8% 71.1% 68.0%

 Oligodendroglial/Mixed gliomas - - 0.0% 11.1% 11.6% 10.6% 10.8% 10.5% 11.5% 3.3% 2.8% 3.8% 4.3% 3.7% 5.2% 13.1% 12.7% 13.7%

 Ependymal tumours 4.2% - 5.1% 3.3% 3.4% 3.1% 6.6% 4.8% 9.8% 8.0% 6.4% 9.6% 4.9% 3.9% 6.4% 4.4% 3.9% 5.1%

 Gliomas of uncertain origin 5.0% - 8.5% 2.6% 3.0% 2.1% - - - 2.8% 3.7% - 6.5% 6.8% 6.1% 3.0% 3.1% 2.9%

 Embryonal tumours 5.8% 4.9% 6.8% 5.5% 6.1% 4.8% 10.8% 10.5% 11.5% 12.7% 11.0% 14.4% 14.7% 17.1% 11.3% 5.0% 5.3% 4.5%

 Medulloblastoma 2.5% - - 4.3% 4.9% 3.5% 9.0% 9.5% 8.2% 10.3% 9.2% 11.5% 11.2% 13.4% 8.1% 3.4% 3.9% 2.8%

 Other 3.3% - 5.1% 1.3% 1.2% 1.4% 1.8% - - 2.3% - 2.9% 3.5% 3.7% 3.2% 1.6% 1.5% 1.7%

Unspecified tumours - 0.0% - 0.8% 0.4% 1.4% - - 0.0% 0.0% 0.0% 0.0% 2.1% 2.1% 2.0% 0.6% 0.6% 0.7%

Other specified types 5.8% 8.2% - 5.5% 5.3% 5.9% 5.4% 6.7% - 5.6% 5.5% 5.8% 7.0% 6.6% 7.6% 3.8% 3.1% 4.9%

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡The histologic types are included if they are higher than 1% in total in any of the MECC registries; percentages should sum over a column to 100% (with some rounding). Where a percentage has been suppressed because it is based on only 1 or 2 cases, the 

remaining percentages may not sum to 100%.
 116 MECC Monograph 

Brain and Other Central Nervous System Cancer Chapter 12

Figure 12.2. Malignant Brain and Other Central Nervous System Cancer: Age-Specific Incidence 

Rates by Country

Males and Females, 5-Year Age Groups

0

5

10

15

20

25

<5

5-9

10--14

15-19

20-24

25-29

30-34

35-39

40-44

45-4950-54

55-59

60-64

65-69

70-74

75+

Age (Yrs)

Incidence Rate per 100,000

Males, 10-Year Age Groups

0

5

10

15

20

25

30

5-14 15-24 25-34 35-44 45-54 55-64 65-74 75+

Age (Yrs)

Incidence Rate per 100,000

Females, 10-Year Age Groups

0

5

10

15

20

25

30

5-14 15-24 25-34 35-44 45-54 55-64 65-74 75+

Age (Yrs)

Incidence Rate per 100,000

US SEER

Israel (Jews)

Israel (Arabs)

Cyprus

Jordan

Egypt
 MECC Monograph 117

Brain and Other Central Nervous System Cancer Chapter 12

Table 12.3. Brain and Other Central Nervous System Cancer: Number of Cases, Age Distribution, and Age-Standardized Incidence Rates, by 

Age and Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001*

Cyprus

1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

1996-2001

Egypt

1999-2001

Jordan 

1996-2001

US SEER†

1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 150 79 71 1,690 939 751 200 122 78 324 165 159 875 506 369 7,060 3,964 3,096

Age Groups (Distribution)

<20 y 17.3% 15.2% 19.7% 13.2% 12.7% 13.8% 35.5% 37.7% 32.1% 21.6% 20.0% 23.3% 33.7% 34.8% 32.2% 13.9% 13.6% 14.2%

20-49 y 22.0% 25.3% 18.3% 24.3% 26.9% 20.9% 28.0% 26.2% 30.8% 44.8% 41.2% 48.4% 35.9% 36.4% 35.2% 28.1% 28.9% 27.0%

50-69 y 40.0% 40.5% 39.4% 36.9% 36.5% 37.3% 27.5% 27.0% 28.2% 28.7% 35.2% 22.0% 26.3% 23.9% 29.5% 31.1% 33.0% 28.8%

70+ y 20.7% 19.0% 22.5% 25.7% 23.9% 28.0% 9.0% 9.0% 9.0% 4.9% 3.6% 6.3% 4.1% 4.9% 3.0% 26.9% 24.5% 29.9%

Age Groups (Rates)‡

Total rate 4.9 5.2 4.6 5.2 6.1 4.3 3.9 4.8 3.0 3.7 3.8 3.5 4.0 4.4 3.6 5.2 6.2 4.4

<20 y 3.4 2.9 4.0 2.3 2.3 2.2 2.0 2.5 1.5 1.4 1.3 1.5 1.9 2.3 1.6 3.0 3.2 2.8

20-49 y 2.7 3.3 2.1 3.4 4.3 2.6 2.2 2.6 1.8 3.5 3.3 3.7 3.3 3.7 2.9 3.6 4.1 3.0

50-69 y 11.5 12.8 10.4 13.4 15.9 11.3 10.2 12.5 8.1 8.8 11.1 6.6 10.1 10.1 10.0 11.2 14.0 8.7

70+ y 15.1 17.0 13.6 18.9 23.2 15.8 13.6 18.8 9.5 8.1 6.1 9.7 7.8 11.3 4.5 20.2 25.6 16.4

*“[Numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Rates are per 100,000 and are age-standardized to the World Standard Million.

countries (Table 12.3), again owing to the striking differences in age 

structures of the populations. Approximately two-thirds of cases in 

Jordanians, Egyptians, and Israeli Arabs occurred among persons 

younger than 50 years of age, and less than 10% occurred among 

persons 70 years or older among these populations. The majority 

of cases in Cypriots, Israeli Jews, and US SEER occurred among 

persons older than 50 years. The incidence rates in males relative 

to females varied by age, with a higher rate in females for ages 

less than 20 years in Cyprus and Egypt (Table 12.3). However the 

numbers of cases were small.

Histology 

As seen in Table 12.2, astrocytic tumors were the most common type 

of brain and other CNS cancers in all MECC countries and in US 

SEER. Embryonal tumors (primarily medulloblastoma) accounted 

for higher proportions of all brain/CNS cancers in Jordanians, 

Egyptians, and Israeli Arabs than in the other populations. 

Oligodendroglioma and mixed glioma accounted for higher 

proportions of all CNS cancers among Israeli Jews and Arabs and in 

US SEER than in other countries. 
 118 MECC Monograph 

Brain and Other Central Nervous System Cancer Chapter 12

SUMMARY AND CONCLUSIONS 

Incidence rates in the MECC countries are in the mid-range of 

those represented in a worldwide sampling of cancer registries, with 

Israeli Jews closer to the high end and Egyptians, Israeli Arabs, and 

Jordanians toward the lower end [23]. Because so little is known 

about the etiology of brain/CNS cancer, it is difficult to interpret 

results in terms of known risk factors. One factor that may influence 

the incidence rate in these countries is the known trend for incidence 

to increase with increasing socioeconomic status. World Bank 

statistics indicate that Israel has a much higher GNP than either 

Jordan or Egypt (data for Cyprus were not available) and, within 

Israel, Jews have a higher socioeconomic status than Arabs [40].

What is clear is that brain/CNS cancer affects different age groups in 

these Middle Eastern countries. In Jordanians, Egyptians, and Israeli 

Arabs, it is primarily a disease of children and young adults. In 

Cypriots and Israeli Jews, as in the US SEER population, it is more 

often a disease of middle or old age. This is overwhelmingly due 

to differences in population age structure, rather than to underlying 

incidence rates. Differences in tumor subsite and histology mirror 

the age differences, as childhood cancers are much more likely to 

be infratentorial and embryonal or ependymal. Other interesting 

epidemiologic patterns include variable male-to-female ratios in 

incidence by country and age, and the general similarity of agespecific incidence rates at young and middle ages. A surprising 

finding was the high proportion of brain cancers with unspecified 

subsite. Although there has been progress in treating some types of 

brain cancer, the fatality rate for most types is still high [41]. This 

analysis did not address differences in survival by country. 

While these data are limited both by the relatively small number of 

cases and the short time period, they do provide new understanding 

about brain and other CNS tumors in the Middle East. Some of the 

patterns appear to be related to variation in the age distribution, and 

possibly access to medical care, of the 5 Middle Eastern populations. 

The heavy burden that brain cancers put on patients, their families, 

and society suggests that collection of additional data would be 

worthwhile. 

REFERENCES

[1] Russell DS, Rubenstein LJ. Pathology of tumours of the nervous system. 

Baltimore (MD): Williams and Wilkins; 1989.

[2] Inskip PD, Linet MS, Heineman EF. Etiology of brain tumors in adults. 

Epidemiol Rev 1995;17:382-414.

[3] Preston-Martin S, Mack WJ. Neoplasms of the nervous system. In: Schottenfeld D, Fraumeni JF, Jr., editors. Cancer epidemiology and prevention. 

New York (NY): Oxford University Press; 1996. p. 1231-81.

[4] Wrensch M, Minn Y, Chew T, Bondy M, Berger MS. Epidemiology 

of primary brain tumors: current concepts and review of the literature. 

Neuro-Oncol 2002;4:278-99.

[5] Malkin D, Jolly KW, Barbier N, Look AT, Friend SH, Gebhardt MC, 

et al. Germline mutations of the p53 tumor-suppressor gene in children 

and young adults with second malignant neoplasms. N Engl J Med 

1992;326:1309-15.

[6] Hisada M, Garber JE, Fung CY, Fraumeni JF, Jr., Li FP. Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 

1998;90:606-11.

[7] Eng C, Maher ER. Dominant genes and phakomatoses associated with 

multiple primary cancers. In: Neugut AI, Meadows AT, Robinson E, editors. Multiple primary cancers. Philadelphia (PA): Williams and Wilkins; 

1999. p. 165-95.

[8] Nichols KE, Malkin D, Garber JE, Fraumeni JF, Jr., Li FP. Germ-line p53 

mutations predispose to a wide spectrum of early-onset cancers. Cancer 

Epidemiol Biomarkers Prev 2001;10:83-7.

[9] Narod SA, Stiller C, Lenoir GM. An estimate of the heritable fraction of 

childhood cancer. Br J Cancer 1991;63:993-9.

[10] Ron E, Modan B, Boice JD, Jr., Alfandary E, Stovall M, Chetrit A, et al. 

Tumors of the brain and nervous system after radiotherapy in childhood. 

N Engl J Med 1988;319:1033-9.
 MECC Monograph 119

Brain and Other Central Nervous System Cancer Chapter 12

[11] Neglia JP, Meadows AT, Robison LL, Kim TH, Newton WA, Ruymann 

FB, et al. Second neoplasms after acute lymphoblastic leukemia in childhood. N Engl J Med 1991;325:1330-6.

[12] Karlsson P, Holmberg E, Lundell M, Mattsson A, Holm LE, Wallgren A. 

Intracranial tumors after exposure to ionizing radiation during infancy: 

a pooled analysis of two Swedish cohorts of 28,008 infants with skin hemangioma. Radiat Res 1998;150:357-64.

[13] Little MP, de Vathaire F, Shamsaldin A, Oberlin O, Campbell S, Grimaud 

E, et al. Risks of brain tumour following treatment for cancer in childhood: modification by genetic factors, radiotherapy and chemotherapy. Int 

J Cancer 1998;78:269-75.

[14] Preston DL, Ron E, Yonehara S, Kobuke T, Fujii H, Kishikawa M, et al. 

Tumors of the nervous system and pituitary gland associated with atomic 

bomb radiation exposure. J Natl Cancer Inst 2002;94:1555-63.

[15] Sadetzki S, Chetrit A, Freedman L, Stovall M, Modan B, Novikov I. 

Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for tinea capitis. Radiat Res 2005;163:424-32.

[16] Inskip PD, Tarone RE, Hatch EE, Wilcosky TC, Shapiro WR, Selker 

RG, et al. Cellular-telephone use and brain tumors. N Engl J Med 

2001;344:79-86.

[17] Kleinerman RA, Linet MS, Hatch EE, Tarone RE, Black PM, Selker RG, 

et al. Self-reported electrical appliance use and risk of adult brain tumors. 

Am J Epidemiol 2005;161:136-46.

[18] Modan B, Wagener DK, Feldman JJ, Rosenberg HM, Feinleib M. Increased mortality from brain tumors: a combined outcome of diagnostic 

technology and change of attitude toward the elderly. Am J Epidemiol 

1992;135:1349-57.

[19] Legler JM, Ries LA, Smith MA, Warren JL, Heineman EF, Kaplan RS, 

et al. Brain and other central nervous system cancers: recent trends in 

incidence and mortality. J Natl Cancer Inst 1999;91:1382-90.

[20] Preston-Martin S. Descriptive epidemiology of primary tumors of the 

brain, cranial nerves and cranial meninges in Los Angeles County. Neuroepidemiology 1989;8:283-95.

[21] Inskip PD, Tarone RE, Hatch EE, Wilcosky TC, Fine HA, Black PM, et 

al. Sociodemographic indicators and risk of brain tumours. Int J Epidemiol 2003;32:225-33.

[22] Lutz WK, Fekete T. Endogenous and exogenous factors in carcinogenesis: 

limits to cancer prevention. Int Arch Occup Environ Health 1996;68:120-

5.

[23] Parkin DM, Whelan SL, Ferlay J, Teppo L, editors. Cancer incidence in 

five continents, volume VIII. IARC Scientific Publication No. 155. Lyon 

(France): International Agency for Research on Cancer; 2002.

[24] Hatch EE, Linet MS, Zhang J, Fine HA, Shapiro WR, Selker RG, et al. 

Reproductive and hormonal factors and risk of brain tumors in adult 

females. Int J Cancer 2005;114:797-805.

[25] Wrensch M, Lee M, Miike R, Newman B, Barger G, Davis R, et al. 

Familial and personal medical history of cancer and nervous system 

conditions among adults with glioma and controls. Am J Epidemiol 

1997;145:581-93.

[26] Schlehofer B, Blettner M, Preston-Martin S, Niehoff D, Wahrendorf J, 

Arslan A, et al. Role of medical history in brain tumour development. 

Results from the international adult brain tumour study. Int J Cancer 

1999;82:155-60.

[27] Wrensch M, Weinberg A, Wiencke J, Miike R, Barger G, Kelsey K. Prevalence of antibodies to four herpesviruses among adults with glioma and 

controls. Am J Epidemiol 2001;154:161-5.

[28] Brenner AV, Linet MS, Fine HA, Shapiro WR, Selker RG, Black PM, et 

al. History of allergies and autoimmune diseases and risk of brain tumors 

in adults. Int J Cancer 2002;99:252-9.

[29] Wiemels JL, Wiencke JK, Sison JD, Miike R, McMillan A, Wrensch M. 

History of allergies among adults with glioma and controls. Int J Cancer 

2002;98:609-15.

[30] Wiemels JL, Wiencke JK, Patoka J, Moghadassi M, Chew T, McMillan A, 

et al. Reduced immunoglobulin E and allergy among adults with glioma 

compared with controls. Cancer Res 2004;64:8468-73.

[31] Sivak-Sears NR, Schwartzbaum JA, Miike R, Moghadassi M, Wrensch 

M. Case-control study of use of nonsteroidal antiinflammatory drugs and 

glioblastoma multiforme. Am J Epidemiol 2004;159:1131-9.

[32] Pardridge WM. Introduction to the blood-brain barrier. Methodology, 

biology and pathology. Cambridge (MA): Cambridge University Press; 

1998.
120 MECC Monograph 

Brain and Other Central Nervous System Cancer Chapter 12

[33] Druckrey H. Specific carcinogenic and teratogenic effects of ‘indirect’ 

alkylating methyl and ethyl compounds, and their dependency on stages 

of ontogenic developments. Xenobiotica 1973;3:271-303.

[34] Kleihues P, Lantos PL, Magee PN. Chemical carcinogenesis in the nervous system. Int Rev Exp Pathol 1976;15:153-232.

[35] Magee PN, Montesano R, Preussmann R. N-nitroso compounds and 

related carcinogens. In: Searle CE, editor. Chemical carcinogens, ACS 

monograph 173. Washington (DC): American Chemical Society; 1976. p. 

491-625.

[36] Kleihues P, Aguzzi A, Wiestler OD. Cellular and molecular aspects of 

neurocarcinogenesis. Toxicol Pathol 1990;18:193-203.

[37] Preston-Martin S, Henderson BE. N-nitroso compounds and human intracranial tumours. IARC Sci Publ 1984;887-94.

[38] Preston-Martin S. Epidemiological studies of perinatal carcinogenesis. 

In: Napalkov NP, Rice JM, Tomatis L, Yamasaki H, editors. Perinatal and 

multigenerational carcinogenesis. Lyon (France): International Agency for 

Research on Cancer; 1989. p. 289-314.

[39] Sadetzki S, Modan B, Chetrit A, Freedman L. An iatrogenic epidemic of 

benign meningioma. Am J Epidemiol 2000;151:266-72.

[40] Finfacts Ireland. Finfacts Reports/Services: global income per capita 

- published 2005. 2005. Available at: http://www.finfacts.com/biz10/globalworldincomepercapita.htm. [Last Accessed: 1/06].

[41] Kleihues P, Cavenee WK. Pathology and genetics of the nervous system. 

Lyon (France): International Agency for Research on Cancer; 1997.
 MECC Monograph 121

Thyroid Cancer Chapter 13

CÉCILE RONCKERS, ELAINE RON

BACKGROUND

Malignancies of the thyroid gland are relatively rare worldwide, but 

incidence has steadily increased over the last few decades. Among 

US females, thyroid cancer accounts for about 3% of all cancers and 

is the eighth most common malignancy [1]. In contrast, in Kuwait, 

thyroid cancer ranks second, comprising 8% of all female cancers, 

and similar findings have been reported for other countries in the 

Gulf region [2]. Thyroid cancer is less common among males, with 

a female-to-male ratio ranging from 2:1 to 5:1 in most populations 

[3]. The age distribution of thyroid malignancies differs from most 

other malignancies, with thyroid tumors occurring at an earlier age 

[4]. 

The majority of thyroid cancers are differentiated carcinomas of the 

papillary or follicular type, which typically have a good prognosis 

and 5-year survival rates close to or higher than 90% [4]. The 

major risk factor for differentiated papillary carcinoma is radiation 

exposure in childhood, as has been shown among children who had 

radiotherapy for benign or malignant conditions [5], survivors of 

the Japanese atomic bombings [6], and persons exposed to radiation 

from nuclear testing [7,8] or the Chernobyl disaster [9]. A history of 

benign thyroid conditions, most notably thyroid nodules and goiter, 

also appears to be a risk factor for both papillary and follicular 

thyroid cancer [10]. Other suggested etiologic factors include female 

hormonal and reproductive characteristics [2,11,12] and cruciferous 

vegetable intake (protective) [13]. Thyroid cancer incidence varies 

according to dietary iodine levels. Iodine deficiency and endemic 

goiter are related to increased risk of follicular thyroid cancer, 

whereas an iodine-rich diet is possibly associated with increased 

risk of papillary thyroid cancer [14]. In a large pooled analysis, fish 

intake was associated with decreased risk of thyroid cancer among 

iodine-deficient populations [15]. Smokers have a decreased risk of 

thyroid cancer, although the biologic mechanism of this finding is 

unclear [16]. Familial occurrences of papillary thyroid cancer have 

been described in rare instances [17], as well as the joint occurrence 

of papillary thyroid cancer and colon cancer in families affected by 

familial adenomatous polyposis [17]. Follicular thyroid cancer and 

breast cancer occur in families with Cowden disease [18].

Medullary thyroid cancers arise from the C-cells, and they account 

for 5%-10% of all thyroid cancers. Up to 25% of medullary cancers 

are thought to be genetically determined, as part of 3 family cancer 

syndromes: familial medullary thyroid cancer, multiple endocrine 

neoplasia (MEN) 2a, and MEN 2b, all of which have been related 

to specific mutations in the RET proto-oncogene [19]. Certain 

medical conditions, including thyroid nodules, were associated with 

increased risk of medullary thyroid cancer in a recent international 

pooled analysis [20].

Anaplastic thyroid cancers are very rare (usually <15% of all thyroid 

cancers), aggressive, metastatic, and rapidly growing tumors that 

are among the most lethal human malignancies, with few patients 

surviving diagnosis beyond a year [21]. These cancers typically 

are diagnosed later in life than other thyroid malignancies, and a 

large proportion are thought to arise from untreated differentiated 

cancers. Due to the rarity of anaplastic thyroid cancers, few etiologic 

investigations have been conducted; nevertheless, radiation exposure 

and thyroid disorders have been reported as risk factors [21].

RESULTS

Overall Incidence

Thyroid cancer age-standardized incidence rates (ASRs) vary 

considerably across the globe, as shown for selected countries in 

Figure 13.1. The overall incidence of thyroid cancer in the Middle 
122 MECC Monograph 

Thyroid Cancer Chapter 13

East Cancer Consortium (MECC) countries from the period 1996 to 

2001 was distributed across the international spectrum, with high 

rates for Israeli Jews and low rates for Egyptians. Only Icelanders 

had higher rates than Israeli Jews (Figure 13.1). 

As shown in Figure 13.1, thyroid cancer ASRs among females were 

lowest in Bombay, India (2.0). Rates among females in MECC 

countries were intermediate – 2.7 for Egyptians, 4.5 for Jordanians, 

6.5 for Israeli Arabs, and 8.6 for Cypriots – except for the very 

high rates for Israeli Jews (11.2). On an additive scale, the rates 

among males had a tighter range, i.e., from 0.8 in Bombay to 4.3 in 

Iceland. From a multiplicative point of view, however, the difference 

was less pronounced: 6.3-fold and 5.7-fold for females and males, 

respectively. Level of medical care and surveillance practices are 

thought to contribute to international variation, because thyroid 

malignancies can remain indolent and undetected for many years. 

In all countries, the ASRs for females were at least twice as high as 

those for males, with ratios lower than 3 in Egypt and Jordan, and 

above 3 in Israel and Cyprus; these findings are similar to those 

from an earlier case series of Israeli Arabs [22]. 

The especially high thyroid cancer ASRs observed among Israeli 

Jews is of interest because high rates also were observed in some 

[23-25], though not all, epidemiologic studies [26] of Jewish 

communities in the United States. These findings may indicate a 

role for genetic factors, as has been seen for breast cancer [27], 

although none have been identified so far. A possible effect of 

medical radiation exposure is discussed in more detail under “Age.” 

McCredie et al. [28] compared Middle Eastern immigrants in 

Australia to native Australians and found higher rates of thyroid 

cancer, but lower rates of smoking-, alcohol-, and Western dietrelated cancers among the immigrants. Although smokers usually 

have lower rates of thyroid cancer than nonsmokers [16], the 

opposite was observed in a recent case-control study in Kuwait [14].

Age

Thyroid cancer contributed a small proportion of all cancers 

diagnosed annually in the MECC populations, ranging from 1.5% 

in Egyptians to 3.8% in Israeli Arabs, although the proportion was 

almost always higher than in the US SEER registries (1.7%) (see 

Table 1.6). This pattern may be related to differences in the age 

structure of the populations. Although the burden of thyroid cancer 

relative to other malignancies was small in the MECC countries, 

there was considerable variation in incidence by age. Table 13.1 

shows the proportion of cases by age for each country and in 

the United States. In all Middle Eastern countries as well as the 

United States, patients aged 30-49 years at diagnosis contributed a 

substantial proportion of thyroid cancers, ranging from more than 

30% to nearly 50% of all cases. Over 70% of thyroid cancers among 

female Cypriots, Israeli Arabs, and Jordanians occurred among 

patients younger than 50 years, compared with approximately 50% 

among female Israeli Jews and Egyptians. Likewise, among males, 

patients younger than 50 years contributed approximately 70% of 

cases among Israeli Arabs and Jordanians. In Cypriots, Israeli Jews, 

and Egyptians, from 40% to a little more than 50% of the cases in 

males occurred before age 50 years. 

These distributions partly reflect the typical younger age at 

diagnosis of thyroid cancer compared with other cancers, but also 

the age structure of the underlying populations. Approximately 

90% of Jordanians, Egyptians, and Israeli Arabs were younger 

than 50 years of age in 1996-2001 (see Figure 1.1). However, the 

contribution of those under age 50 to the total thyroid cancer cases 

was lower for Egyptians compared with Jordanians and Israeli 

Arabs. Other case series have shown that thyroid cancer is, on 

average, diagnosed at a younger age in the Middle East compared 

with the average age of 45 years in the United States [1]; e.g., the 

mean ages were 32 years in Israeli Arabs [22], 35 years in Kuwaitis 

[2], and 38 years in Yemenites [29]. This variation in age at 

diagnosis could be entirely due to the much younger age structure of 

the populations in these countries, compared with the United States 
 MECC Monograph 123

Thyroid Cancer Chapter 13

Figure 13.1 Thyroid Cancer: Age-Standardized Incidence 

 Rates* by Country†

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Iceland

Israel (Jews)

Japan: H iro shima

USA : H awaii (Whites)

C yprus

USA : SEER (Whites)

Kuwait (Kuwaitis)

Israel (A rabs)

A ustralia: N ew So uth Wales

Singapo re (C hinese)

Oman

Jo rdan

C zech R epublic

USA : SEER (B lacks)

Sweden

Egypt

UK: Sco tland

India: B o mbay

Female

M ale

Age-Standardized Incidence Rate 

*Rates are per 100,000 and are age-standardized to the World Standard Million.

†Data for most countries listed are for 1993-1997 and are from: Parkin DM, Whelan SL, Ferlay J, Teppo L, 

editors. Cancer incidence in five continents, volume VIII. IARC Scientific Publication No. 155. Lyon (France):

International Agency for Research on Cancer; 2002. However, data for the following countries are taken

from this monograph: Egypt (1999-2001); Israel (Arabs and Jews) and Jordan (1996-2001).
124 MECC Monograph 

Thyroid Cancer Chapter 13

Table 13.1. Thyroid Cancer: Number of Cases, Age Distribution, and Age-Standardized Incidence Rates, by Age and Sex, in Cyprus, Israel (Jews and Arabs), 

Egypt, Jordan, and US SEER − 1996-2001*

Cyprus Israel (Jews) Israel (Arabs) Egypt Jordan US SEER†

1998-2001 1996-2001 1996-2001 1999-2001 1996-2001 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 179 40 139 2,404 546 1,858 227 45 182 154 45 109 617 172 445 8,684 2,152 6,532

Age Groups (Distribution)

<20 y 4.5% 0.0% 5.8% 2.2% 2.6% 2.2% 4.0% 0.0% 4.9% 4.5% 6.7% 3.7% 7.1% 7.6% 7.0% 2.3% 1.9% 2.4%

20-29 y 15.1% 15.0% 15.1% 11.1% 7.5% 12.1% 25.1% 26.7% 24.7% 9.1% - 11.9% 22.0% 19.2% 23.1% 10.9% 6.9% 12.2%

30-39 y 25.7% 20.0% 27.3% 12.1% 11.2% 12.4% 28.2% 24.4% 29.1% 18.8% 11.1% 22.0% 26.3% 24.4% 27.0% 20.2% 15.7% 21.7%

40-49 y 20.1% 12.5% 22.3% 21.8% 18.9% 22.7% 19.8% 20.0% 19.8% 20.8% 33.3% 15.6% 16.5% 19.2% 15.5% 23.7% 22.6% 24.1%

50-59 y 19.0% 30.0% 15.8% 20.2% 20.3% 20.2% 11.0% 8.9% 11.5% 20.1% 22.2% 19.3% 12.3% 14.0% 11.7% 19.3% 22.9% 18.1%

60+ y 15.6% 22.5% 13.7% 32.5% 39.6% 30.4% 11.9% 20.0% 9.9% 26.6% 24.4% 27.5% 15.7% 15.7% 15.7% 23.5% 30.0% 21.3%

Age Groups (Rates)‡ 

Total rate 5.6 2.6 8.6 7.5 3.5 11.2 4.1 1.8 6.5 2.0 1.2 2.7 3.0 1.7 4.5 6.2 3.2 9.2

<20 y 0.8 0.0 1.6 0.5 0.3 0.8 0.3 0.0 0.6 0.1 0.1 0.1 0.3 0.2 0.4 0.5 0.2 0.9

20-29 y 6.8 3.1 10.2 5.9 1.8 10.1 4.5 1.9 7.3 0.8 - 1.5 2.4 1.1 4.0 5.6 1.7 9.7

30-39 y 11.2 4.0 17.9 8.1 3.4 12.6 6.7 2.3 11.3 2.0 0.7 3.3 4.9 2.5 7.5 9.3 3.5 15.1

40-49 y 9.5 2.7 16.2 14.1 5.7 22.0 8.1 3.4 12.8 2.9 2.7 3.3 5.4 3.5 7.3 11.6 5.6 17.6

50-59 y 11.3 8.0 14.6 18.6 8.9 27.6 7.2 2.3 12.1 4.9 3.2 6.7 5.3 3.2 7.5 13.3 8.1 18.3

60+ y 6.7 4.9 8.2 18.1 10.9 24.0 7.9 5.7 9.9 6.6 3.9 9.2 7.4 4.0 10.8 12.5 8.9 15.4

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Rates are per 100,000 and are age-standardized to the World Standard Million.

(see Figure 1.1). It is important to note that fewer than 200 thyroid 

cancer cases were observed in Egypt and in Cyprus, which can cause 

considerable imprecision in the incidence estimates, particularly 

when evaluating sex- and age-specific subgroups (Table 13.1).

Analyses of age-specific incidence rates, standardized to the world 

population, provided a better comparison across populations, 

irrespective of the age structure of the underlying populations (Table 

13.1 and Figures 13.2 and 13.3). In most populations, the incidence 

of thyroid cancer rose with increasing age up to 45-55 years and then 

reached a plateau. There was some variation in this pattern across 

individual countries at ages 60 and older; e.g., there seemed to be 

a decrease in Cyprus, which may be due to the fine stratification 

and thus very small number of cases (only 28 cases in persons older 

than 60 years) available for that analysis. Among females, the most 

striking pattern appears for Israeli Jews, with incidence rates among 

younger individuals comparable to the US and Cypriot populations, 

but with the highest rate of any subgroup studied (24-27) for those 
 MECC Monograph 125

Thyroid Cancer Chapter 13

0

5

10

15

20

25

30

35

0-04 05-09 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75+

Age

Israel (Jews)

Jordan

US SEER*

Israel (Arabs)

Egypt

Cyprus

Incidence Rate per 100,000

Figure 13.2. Thyroid Cancer: Age-Specific Incidence Rates for Females in Cyprus, Israel (Jews and

Arabs), Egypt, Jordan, and US SEER – 1996-2001

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
126 MECC Monograph 

Thyroid Cancer Chapter 13

0

2

4

6

8

10

12

14

0-04 05-09 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75+

Age

Israel (Jews)

Jordan

US SEER*

Israel (Arabs)

Egypt

Cyprus

Incidence Rate per 100,000

Figure 13.3. Thyroid Cancer: Age-Specific Incidence Rates for Males in Cyprus, Israel

(Jews and Arabs), Egypt, Jordan, and US SEER � 1996-2001

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
 MECC Monograph 127

Thyroid Cancer Chapter 13

older than 50 years (Table 13.1). This effect was slightly less 

pronounced among older Israeli Jewish males, although their rates 

also were higher than in most of the other countries. 

The marked peak among 50-year-old Israeli Jews (Figure 13.3), 

compared with the smooth comparable age-specific curve from 

the US SEER registry, is thought provoking. This group of Israeli 

Jews includes those who received x-ray treatments for tinea capitis 

as children in the 1950s and are consequently known to be at 

substantially increased risk of thyroid cancer [30]. Although the 

number of exposed Israelis is estimated to be approximately 20,000, 

this number may be too small to have much influence on national 

rates. An increase in Israeli national rates of brain meningioma 

attributable to this radiation treatment was discernible, however 

[31]. In the future, Israeli thyroid cancer incidence patterns should 

be studied by country of origin because the large majority of 

irradiated individuals or their families immigrated to Israel from 

North Africa.

Histology

Microscopic confirmation for thyroid cancer was very high: over 

99% in Cyprus, Jordan, and the United States, and between 93% and 

95% in the other MECC countries (Table 13.2). These percentages 

represent a clear strength of the data presented in this chapter. 

Analyses limited to microscopically confirmed cases allowed for 

stratification by histologic type. Differentiated carcinoma (papillary 

and follicular subtypes) made up 90% to 94% of all thyroid cancers 

in Cyprus, Israel, Jordan, and the United States. The exception was 

Egypt, where only 73% of the thyroid cancers were differentiated. 

Some larger differences among countries emerged when more 

detailed histology was evaluated. Papillary carcinoma made up 80% 

or more of the thyroid cancers in Cypriots, Israeli Arabs and Jews, 

and the US population, whereas its contribution was considerably 

lower in Jordanians (77%) and Egyptians (62%). Medullary and 

anaplastic thyroid cancers were rare and contributed only 1% to 4%, 

except for Egypt, where 14% of all thyroid cancers were anaplastic. 

Earlier case series in Middle Eastern countries reported lower 

proportions of papillary carcinoma – e.g., 66% among Israeli Arabs 

in Northern Israel in the 1990s [22], and 58% in Kuwaitis in the 

1970s [32]. These differences may be related to improved diagnostic 

tools and the change in the classification of the follicular variant of 

papillary carcinoma, which used to be classified as a separate entity, 

but is now considered papillary thyroid cancer [33]. Moreover, the 

earlier series were not population based and therefore were less 

reliable than current estimates. Historical comparisons for these 

MECC cancer registries were not possible because an earlier report 

did not include results for thyroid cancer [34].

After appropriate adjustment for the age structure of the populations, 

the incidence rates for each histologic type of thyroid cancer were 

very low. Annual papillary cancer rates varied from 1.0 in Egyptians 

to 5.9 in Israeli Jews, whereas follicular cancer rates varied from 

0.2 in Egyptians to 0.6 in Israeli Arabs and Jews, as well as in US 

SEER. The ratio of papillary to follicular thyroid cancers varied 

from around 5.0 among Israeli Arabs, Egyptians, and Jordanians, 

to 8.2 among Americans, 9.8 among Israeli Jews, and 12.2 among 

Cypriots. Countries with the lower ratio of papillary cancer to 

follicular cancer tended to be those with young populations and 

generally lower socioeconomic status, but it is difficult to draw 

conclusions because the small numbers of cases make the rates 

unstable. The female-to-male ratios were close to 3:1 for both 

types of cancer, except for follicular cancer among Israeli Arabs, 

which had a ratio of 10:1. In accordance with the high proportion of 

anaplastic cases mentioned earlier, the incidence rate of anaplastic 

thyroid cancer was much higher in Egypt (0.3) than in the other 

countries (0.0-0.1), which might reflect differences in access to 

medical care. Unpublished MECC data on disease stage have shown 

a pattern of more advanced stage at diagnosis in Egypt compared 

with other MECC countries for several other malignancies (Laurence 

Freedman, e-mail message to author, March 1, 2005), lending 

credibility to this hypothesis. Alternatively, the high incidence of 

anaplastic thyroid cancer in Egypt might be due to other, currently 

unknown factors. It is interesting to note that premenopausal breast 
128 MECC Monograph 

Thyroid Cancer Chapter 13

Table 13.2. Thyroid Cancer: Number of Cases, Proportions of Microscopic Confirmation and Histologic Type, and Age-Standardized Incidence Rates for 

Histologic Types, by Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001*

Cyprus Israel (Jews) Israel (Arabs) Egypt Jordan US SEER†

1998-2001 1996-2001 1996-2001 1999-2001 1996-2001 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Microscopically confirmed 100.0% 100.0% 100.0% 93.8% 94.3% 93.6% 95.2% 97.8% 94.5% 92.9% 88.9% 94.5% 100.0% 100.0% 100.0% 99.5% 99.2% 99.6%

Total cases microscopically 

confirmed 179 40 139 2,254 515 1,739 216 44 172 143 40 103 617 172 445 8,642 2,134 6,508

Distribution of Microscopically Confirmed Cases

Histologic distribution 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Carcinoma 98.9% 97.5% 99.3% 99.0% 99.0% 99.0% 99.5% 100.0% 99.4% 96.5% 97.5% 96.1% 99.0% 98.3% 99.3% 99.7% 99.6% 99.8%

 Follicular carcinoma 7.3% 7.5% 7.2% 8.7% 10.3% 8.2% 12.5% - 14.5% 11.2% 12.5% 10.7% 13.5% 10.5% 14.6% 9.5% 11.0% 9.0%

 Papillary carcinoma 86.6% 85.0% 87.1% 82.7% 74.8% 85.0% 81.0% 88.6% 79.1% 62.2% 60.0% 63.1% 76.8% 74.4% 77.8% 83.4% 79.1% 84.8%

 Medullary carcinoma 1.7% - - 3.1% 6.2% 2.2% 4.2% 6.8% 3.5% 2.8% 7.5% - 2.4% 4.7% 1.6% 0.8% 1.4% 0.7%

 Anaplastic carcinoma 2.8% - 2.9% 2.0% 2.7% 1.8% 0.0% 0.0% 0.0% 14.0% 12.5% 14.6% 1.8% - 2.0% 1.2% 1.6% 1.1%

 Other specified carcinoma - 0.0% - 1.7% 3.3% 1.2% - 0.0% - 5.6% - 5.8% 1.6% 2.9% 1.1% 4.0% 5.7% 3.5%

 Unspecified carcinoma 0.0% 0.0% 0.0% 0.8% 1.7% 0.6% - 0.0% - - 0.0% - 2.9% 4.7% 2.2% 0.7% 0.8% 0.7%

Sarcoma - 0.0% - - - 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.2% 0.0%

Unspecified cancer - - 0% 0.9% 0.6% 1.0% - 0.0% - 3.5% - 3.9% 1.0% 1.7% 0.7% 0.2% 0.1% 0.2%

Rates‡

Total rate 5.6 2.6 8.6 7.0 3.3 10.5 4.0 1.8 6.2 1.8 1.0 2.5 3.0 1.7 4.5 6.2 3.1 9.2

Carcinomas 5.6 2.5 8.5 7.0 3.3 10.5 3.9 1.8 6.1 1.7 1.0 2.4 3.0 1.7 4.4 6.2 3.1 9.1

 Follicular carcinoma 0.4 0.2 0.6 0.6 0.3 0.8 0.6 - 1.0 0.2 0.1 0.3 0.4 0.2 0.7 0.6 0.3 0.8

 Papillary carcinoma 4.9 2.2 7.5 5.9 2.5 9.1 3.1 1.5 4.7 1.0 0.5 1.4 2.3 1.2 3.4 5.2 2.5 7.9

 Medullary carcinoma 0.1 - - 0.2 0.2 0.2 0.2 0.2 0.2 0.0 0.1 - 0.1 0.1 0.1 0.1 0.0 0.1

 Anaplastic carcinoma 0.1 - 0.2 0.1 0.1 0.1 0.0 0.0 0.0 0.3 0.2 0.5 0.1 - 0.1 0.1 0.0 0.1

 Other specified carcinoma - 0.0 - 0.1 0.1 0.1 - 0.0 - 0.1 - 0.2 0.1 0.1 0.1 0.2 0.2 0.3

 Unspecified carcinoma 0.0 0.0 0.0 0.0 0.0 0.0 - 0.0 - - 0.0 - 0.1 0.1 0.1 0.0 0.0 0.1

Sarcoma - 0.0 - - - 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0

Unspecified cancer - - 0.0 0.1 0.0 0.1 - 0.0 - 0.1 - 0.1 0.0 0.0 0.0 0.0 0.0 0.0

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Rates are per 100,000 and are age-standardized to the World Standard Million.
 MECC Monograph 129

Thyroid Cancer Chapter 13

cancer in Egypt has been found to be unusually aggressive compared 

with other countries [35,36].

SUMMARY AND CONCLUSIONS

In this comparative analysis of patterns of thyroid cancer incidence, 

MECC countries shared many features, with a few notable 

exceptions. ASRs were distributed across the international spectrum, 

ranging from 2.0 for Egyptians to 7.5 for Israeli Jews. Thyroid 

cancer contributed 1.5% to 3.8% of all cancers diagnosed in the 

MECC countries annually, which was generally higher than the 

proportion in the United States (1.6%). In all these countries, the 

rates for females were at least twice as high as those for males, 

and patients 30-49 years of age at diagnosis contributed the largest 

proportion of cases, ranging from 30% to nearly 50% of all cases, 

depending on the age structure of the underlying population. In most 

countries, the incidence of thyroid cancer rose with increasing age 

up to ages 45-55 years, and then reached a plateau. ASRs among 

Israeli Jewish females older than 50 years of age were particularly 

high – approximately 50% higher than in the United States. The 

microscopic confirmation percentages for thyroid cancer were 

excellent, from 93% to over 99%. Finally, differentiated carcinoma 

accounted for 90%-94% of all thyroid cancers, with the exception 

of Egypt (73%). Also in Egypt, 14% of all thyroid cancers were 

anaplastic, compared with less than 3% in all other MECC countries 

and the United States. 

Further research is indicated, including (1) an analysis of thyroid 

cancer rates by country of origin for Israeli Jews, to address 

the hypothesis that radiation treatment for tinea capitis among 

immigrants from North Africa contributed to the high rates among 

older Israeli Jews; and (2) an evaluation of possible explanations for 

the unfavorable stage distribution for thyroid and other malignancies 

in Egypt.

REFERENCES

[1] American Cancer Society. Cancer facts and figures 2005. Atlanta, GA: 

American Cancer Society; 2005.

[2] Memon A, Darif M, Al Saleh K, Suresh A. Epidemiology of reproductive and hormonal factors in thyroid cancer: evidence from a case-control 

study in the Middle East. Int J Cancer 2002;97:82-9.

[3] Parkin DM, Whelan SL, Ferlay J, Teppo L, eds. Cancer incidence in five 

continents, volume VIII. IARC Scientific Publication No. 155. Lyon 

(France): International Agency for Research on Cancer; 2002.

[4] Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, et 

al. SEER cancer statistics review. 2003. Available at: http://seer.cancer.

gov/csr/1975_2000/. [Last Accessed: 12/05].

[5] Ron E, Lubin JH, Shore RE, Mabuchi K, Modan B, Pottern LM, et al. 

Thyroid cancer after exposure to external radiation: a pooled analysis of 

seven studies. Radiat Res 1995;141:259-77.

[6] Thompson DE, Mabuchi K, Ron E, Soda M, Tokunaga M, Ochikubo S, 

et al. Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 

1958-1987. Radiat Res 1994;137:S17-S67.

[7] Kerber RA, Till JE, Simon SL, Lyon JL, Thomas DC, Preston-Martin S, 

et al. A cohort study of thyroid disease in relation to fallout from nuclear 

weapons testing. JAMA 1993;270:2076-82.

[8] Hamilton TE, van Belle G, LoGerfo JP. Thyroid neoplasia in Marshall 

Islanders exposed to nuclear fallout. JAMA 1987;258:629-35.

[9] Cardis E, Kesminiene A, Ivanov V, Malakhova I, Shibata Y, Khrouch V, 

et al. Risk of thyroid cancer after exposure to 131I in childhood. J Natl 

Cancer Inst 2005;97:724-32.

[10] Franceschi S, Preston-Martin S, Dal Maso L, Negri E, La Vecchia C, 

Mack WJ, et al. A pooled analysis of case-control studies of thyroid cancer. IV. Benign thyroid diseases. Cancer Causes Control 1999;10:583-95.

[11] Negri E, Dal Maso L, Ron E, La Vecchia C, Mark SD, Preston-Martin S, 

et al. A pooled analysis of case-control studies of thyroid cancer. II. Menstrual and reproductive factors. Cancer Causes Control 1999;10:143-55.

[12] La Vecchia C, Ron E, Franceschi S, Dal Maso L, Mark SD, Chatenoud 

L, et al. A pooled analysis of case-control studies of thyroid cancer. III. 
130 MECC Monograph 

Thyroid Cancer Chapter 13

Oral contraceptives, menopausal replacement therapy and other female 

hormones. Cancer Causes Control 1999;10:157-66.

[13] Bosetti C, Negri E, Kolonel L, Ron E, Franceschi S, Preston-Martin S, 

et al. A pooled analysis of case-control studies of thyroid cancer. VII. 

Cruciferous and other vegetables (International). Cancer Causes Control 

2002;13:765-75.

[14] Memon A, Varghese A, Suresh A. Benign thyroid disease and dietary 

factors in thyroid cancer: a case-control study in Kuwait. Br J Cancer 

2002;86:1745-50.

[15] Bosetti C, Kolonel L, Negri E, Ron E, Franceschi S, Dal Maso L, et al. 

A pooled analysis of case-control studies of thyroid cancer. VI. Fish and 

shellfish consumption. Cancer Causes Control 2001;12:375-82.

[16] Mack WJ, Preston-Martin S, Dal Maso L, Galanti R, Xiang M, Franceschi 

S, et al. A pooled analysis of case-control studies of thyroid cancer: cigarette smoking and consumption of alcohol, coffee, and tea. Cancer Causes 

Control 2003;14:773-85.

[17] Malchoff CD, Malchoff DM. The genetics of hereditary nonmedullary 

thyroid carcinoma. J Clin Endocrinol Metab 2002;87:2455-9.

[18] Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, et al. Germline 

mutations of the PTEN gene in Cowden disease, an inherited breast and 

thyroid cancer syndrome. Nat Genet 1997;16:64-7.

[19] Leboulleux S, Baudin E, Travagli JP, Schlumberger M. Medullary thyroid 

carcinoma. Clin Endocrinol (Oxf) 2004;61:299-310.

[20] Negri E, Ron E, Franceschi S, La Vecchia C, Preston-Martin S, Kolonel 

L, et al. Risk factors for medullary thyroid carcinoma: a pooled analysis. 

Cancer Causes Control 2002;13:365-72.

[21] Wiseman SM, Loree TR, Rigual NR, Hicks WL, Jr., Douglas WG, Anderson GR, et al. Anaplastic transformation of thyroid cancer: review of clinical, pathologic, and molecular evidence provides new insights into disease 

biology and future therapy. Head Neck 2003;25:662-70.

[22] Zidan J, Kassem S, Karen D, Kuten A, Robinson E. Differentiated thyroid 

cancer in Arabs in northern Israel [Hebrew]. Harefuah 1997;132:6-9, 72.

[23] Mack TM, Berkel J, Bernstein L, Mack W. Religion and cancer in Los 

Angeles County. Natl Cancer Inst Monogr 1985;69:235-45.

[24] Bross ID, Shimaoka K, Tidings J. Some epidemiological clues in thyroid cancer. Tonsillectomy, acne, allergy, ethnicity. Arch Intern Med 

1971;128:755-60.

[25] Shore RE, Hildreth N, Dvoretsky P, Andresen E, Moseson M, Pasternack 

B. Thyroid cancer among persons given X-ray treatment in infancy for an 

enlarged thymus gland. Am J Epidemiol 1993;137:1068-80.

[26] Ron E, Kleinerman RA, Boice JD, Jr., LiVolsi VA, Flannery JT, Fraumeni 

JF, Jr. A population-based case-control study of thyroid cancer. J Natl 

Cancer Inst 1987;79:1-12.

[27] Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, 

et al. The risk of cancer associated with specific mutations of BRCA1 and 

BRCA2 among Ashkenazi Jews. N Engl J Med 1997;336:1401-8.

[28] McCredie M, Coates M, Grulich A. Cancer incidence in migrants to New 

South Wales (Australia) from the Middle East, 1972-91. Cancer Causes 

Control 1994;5:414-21.

[29] Abdulmughni YA, Al Hureibi MA, Al Hureibi KA, Ghafoor MA, Al 

Wadan AH, Al Hureibi YA. Thyroid cancer in Yemen. Saudi Med J 

2004;25:55-9.

[30] Ron E, Modan B, Preston D, Alfandary E, Stovall M, Boice JD, Jr. 

Thyroid neoplasia following low-dose radiation in childhood. Radiat Res 

1989;120:516-31.

[31] Sadetzki S, Modan B, Chetrit A, Freedman L. An iatrogenic epidemic of 

benign meningioma. Am J Epidemiol 2000;151:266-72.

[32] El Ghamrawi KA, Khalifa MS. Thyroid cancer in Kuwait: review of 117 

cases. Br J Surg 1979;66:139-42.

[33] Hedinger C, Williams ED, Sobin LH, World Health Organization. Histological typing of thyroid tumors. Berlin: Springer-Verlag; 1988.

[34] Kahan E, Ibrahim AS, El Najjar K, Ron E, Al Agha H, Polliack A, et al. 

Cancer patterns in the Middle East – special report from the Middle East 

Cancer Society. Acta Oncol 1997;36:631-6.

[35] Richards MA, Coleman RE, Hamsa R, Khaled H, el Mawla MG, Kadry 

I, et al. Advanced breast cancer in Egyptian women: clinical features and 

response to endocrine therapy. The Anglo-Egyptian Health Agreement 

Collaborative Study. Eur J Surg Oncol 1992;18:219-23.

[36] el-A Helal T, Khalifa A, Kamel AS. Immunohistochemical expression 

of p53 and c-erbB2 proteins in breast cancer in Egypt. Anticancer Res 

2000;20:2145-50.
 MECC Monograph 131

Lymphoma and Leukemia Chapter 14

AMR S. SOLIMAN, PAOLO BOFFETTA

BACKGROUND

In recent years, a new classification of lymphoid and hematopoietic 

malignancies has been adopted, based upon the Revised EuropeanAmerican Lymphoma classification system [1] and the World Health 

Organization (WHO) classification [2]. The new classification 

includes lymphomas, leukemias, and multiple myeloma as one group 

of malignant diseases. 

Lymphomas encompass a diverse group of neoplasms with 

the common characteristic of originating from the cells of the 

lymphopoietic system. Traditionally, 2 main groups of lymphoma 

have been distinguished: Hodgkin Lymphoma (HL), characterized 

by large polynuclear (Reed-Sternberg) cells; and a diverse group of 

other lymphomas, defined as non-Hodgkin lymphomas (NHL). The 

new classification further divides NHL into T-cell NHL and B-cell 

NHL. Lymphocytic leukemias fall within the B-cell NHL group. 

However, in this chapter we will use the traditional classification, 

and lymphocytic leukemia will be counted as leukemia.

The classification of leukemias is complex and has seen several 

changes over the years [3]. The traditional classification, which we 

will use here, includes acute myeloid leukemia, chronic myeloid 

leukemia, acute lymphocytic leukemia, and chronic lymphocytic 

leukemia (CLL). Other types include acute monocytic leukemia, 

other myeloid/monocytic leukemias, other lymphocytic and acute 

leukemias, and aleukemic leukemia. 

Using the traditional classification, NHLs are estimated at 287,000 

new cases in the world annually, HLs at 62,000, and leukemias 

at 257,000. Together, these account for approximately 7% of all 

incident cancers worldwide [4]. 

In general, the etiology of lymphomas and leukemias is not well 

understood. Many studies show groups of risk factors associated 

with both malignancies. 

Etiology of Lymphoma

The risk factors for lymphoma can be classified into 3 groups: 

immunological function, infections, and lifestyle and occupational 

exposures. 

Immunological function. Strong evidence suggests that 

altered immunological function, either immunostimulation or 

immunosuppression, entails an increased risk of lymphoma. For 

example, renal transplant patients have a 30 times greater risk for 

developing lymphoma than the general population. Lymphomas that 

develop in immunosuppressed patients share common characteristics: 

They are generally high-grade B-cell lymphomas, and they are more 

likely to be extranodal and of worse prognosis [5]. Lymphomas have 

been reported for a variety of conditions that are either autoimmune 

in nature or that require immunosuppressive treatment. These include 

rheumatoid arthritis and Sjogrens syndrome [6,7]. An association with 

celiac disease and NHL of the intestinal tract has also been noted [8].

Infections. The biological agents associated with NHL are human 

immunodeficiency virus (HIV), human T-cell lymphotropic virus 1 

(HTLV-1), and Epstein Barr virus (EBV) [9-11]. Hepatitis C virus 

(HCV) [12,13] and human herpes virus 8 (HHV8) have also been linked 

to the development of NHL [10,14,15]. EBV has been shown to be 

particularly prominent in lymphomas developing in immunosuppressed 

patients [16]. EBV has also been implicated as a causal factor in the 

etiology of HL [17]. In addition, infection with Helicobacter pylori is a 

risk factor for gastric lymphoma [18]. 
132 MECC Monograph 

Lymphoma and Leukemia Chapter 14

and with exposure to benzene, synthetic fiber dust, radioactive 

materials, and toluene [22].

RESULTS

Overall Incidence 

Age-standardized incidence rates (ASRs) of NHL in the United 

States have been reported to be among the highest in the world [23]. 

Rates have been reported to be low in East Asia, intermediate in 

Africa and the Middle East, and high in Western Europe, Australia, 

and Canada. International variations reflect differences in exposure 

to risk factors or variable reporting [23].

As shown in Table 14.1, in MECC registries, multiyear averages 

showed very high ASRs for lymphoma among Israeli Jews (18.6) 

and Egyptians (16.3). These rates exceeded the US SEER incidence 

rate (15.3) – considered one of the highest in the world – as well 

as the rates of the other MECC populations. Rates of nodal NHL 

were also higher among Israeli Jews (11.6) and Egyptians (10.0) 

than in the other MECC populations and the US SEER rate (8.3), 

also considered one of the highest worldwide. Extranodal NHL rates 

among Israeli Jews and Egyptians were lower than US SEER, but 

higher than in other MECC populations. 

Among MECC registries, the ASR of HL was highest among Israeli 

Jews (3.4), followed by Cypriots (3.0). Egyptians had the lowest rate 

(2.1). The HL ASRs in US SEER, Jordan, and Israeli Arab registries 

were intermediate (Table 14.1).

For leukemia, the ASR was again the highest among Israeli Jews 

(8.6), a rate slightly lower than the US SEER rate (8.8). Rates 

in other MECC countries were approximately 75% of the rate 

reported among Israeli Jews (Table 14.1). Among the different 

types of leukemia, the most frequent was CLL, which showed the 

NHL is 80 times more frequent among HIV-infected persons 

worldwide than in the general population [19]. The type of HIV 

virus that is generally involved with the development of NHL is 

HIV-1 [5]. About 4% of persons with symptoms from their HIV 

infection develop an NHL each year [19], but this nevertheless 

represents a relatively modest contribution to the overall incidence 

of NHL in countries with a low prevalence of AIDS, such as those 

in the Middle East Cancer Consortium (MECC). The AIDS-related 

lymphomas tend to be high-grade B-cell lymphomas, and more than 

40% occur in uncommon sites such as the brain and heart [20]. 

Recently it has been shown that EBV can infect normal T 

lymphocytes [21]. The clinical manifestation of primary delayed 

EBV infection is infectious mononucleosis. EBV is associated with 

Burkitt’s lymphoma in endemic areas, nasopharyngeal carcinoma, 

and HL, and with NHL among immunosuppressed persons.

Lifestyle and occupational exposures. The third group of putative 

risk factors includes farming, exposure to pesticides and organic 

solvents, tobacco use, alcohol consumption, and sun exposure. 

However, despite extensive research, no conclusions can be drawn 

regarding the role of these factors in lymphomagenesis.

Etiology of Leukemia

The etiology of leukemia remains rather unclear. Ionizing radiation 

is a known cause of leukemia in humans. Other suspected risk 

factors include pesticides; medical conditions such as infectious 

mononucleosis, autoimmune diseases, and immunodeficiency; and 

tonsillectomy.

Except for HTLV-1 and a rare type of leukemia, no viruses or 

infections have been implicated in the etiology of leukemia. Adult 

leukemia has been associated with working in the chemical industry, 
 MECC Monograph 133

Lymphoma and Leukemia Chapter 14

Table 14.1. Lymphoma and Leukemia: Age-Standardized Incidence Rates in Cyprus, Israel (Jews and Arabs), Egypt, 

Jordan, and US SEER – 1996-2001*

Cyprus

 1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER†

 1999-2001

Lymphoma 10.6 18.6 12.9 16.3 8.9 15.3

 Non-Hodgkin lymphoma 7.6 15.2 10.2 14.2 6.4 12.9

 Nodal 5.2 11.6 7.8 10.0 4.7 8.3

 Extranodal 2.4 3.6 2.5 4.1 1.7 4.6

 Hodgkin lymphoma 3.0 3.4 2.7 2.1 2.5 2.4

Leukemia 6.9 8.6 6.4 6.0 6.3 8.8

 Chronic lymphocytic leukemia 1.8 3.0 1.3 1.3 1.1 2.2

*Rates are per 100,000 and are age-standardized to the World Standard Million.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

Table 14.2a. Lymphoma: Number of Cases and Age Distribution, by Sex, of Lymphoma, Hodgkin Lymphoma, and Non-Hodgkin Lymphoma, in Cyprus, Israel 

(Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001*

Cyprus Israel (Jews) Israel (Arabs) Egypt Jordan US SEER†

1998-2001 1996-2001 1996-2001 1999-2001 1996-2001 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases -- All lymphoma 357 194 163 6,638 3,371 3,267 615 346 269 1,316 820 496 1,733 1,042 691 23,698 12,913 10,785

Total cases -- Hodgkin lymphoma 83 37 46 1,030 521 509 166 99 67 218 151 67 639 383 256 3,099 1,706 1,393

Total cases -- Non-Hodgkin lymphoma 274 274 117 5,608 2,850 2,758 449 247 202 1,098 669 429 1,094 659 435 20,599 11,207 9,392

Age Groups (Distribution) for Lymphoma

<50 y 37.8% 37.6% 38.0% 29.9% 32.2% 27.5% 57.1% 60.7% 52.4% 55.2% 58.2% 50.4% 61.1% 63.1% 58.0% 28.0% 30.8% 24.6%

50-69 y 37.0% 38.7% 35.0% 34.2% 34.3% 34.2% 28.6% 26.0% 32.0% 37.2% 34.1% 42.1% 29.3% 28.9% 29.8% 32.7% 34.4% 30.8%

70+ y 25.2% 23.7% 27.0% 35.9% 33.5% 38.4% 14.3% 13.3% 15.6% 7.6% 7.7% 7.5% 9.6% 8.0% 12.2% 39.3% 34.8% 44.6%

Age Groups (Distribution) for Hodgkin Lymphoma

<50 y 84.3% 86.5% 82.6% 74.4% 74.1% 74.7% 83.7% 87.9% 77.6% 84.4% 82.8% 88.1% 83.9% 84.6% 82.8% 71.2% 70.9% 71.6%

50-69 y 15.7% 13.5% 17.4% 15.5% 17.3% 13.8% 12.7% 11.1% 14.9% 14.2% 15.2% 11.9% 12.5% 12.8% 12.1% 17.0% 18.5% 15.1%

70+ y 0.0% 0.0% 0.0% 10.1% 8.6% 11.6% 3.6% - 7.5% 1.4% 2.0% 0.0% 3.6% 2.6% 5.1% 11.8% 10.6% 13.3%

Age Groups (Distribution) for Non-Hodgkin Lymphoma

<50 y 23.7% 26.1% 20.5% 21.7% 24.6% 18.7% 47.2% 49.8% 44.1% 49.5% 52.6% 44.5% 47.8% 50.7% 43.4% 21.5% 24.7% 17.6%

50-69 y 43.4% 44.6% 41.9% 37.7% 37.4% 37.9% 34.5% 32.0% 37.6% 41.7% 38.4% 46.9% 39.0% 38.2% 40.2% 35.1% 36.8% 33.1%

70+ y 32.8% 29.3% 37.6% 40.6% 38.0% 43.3% 18.3% 18.2% 18.3% 8.8% 9.0% 8.6% 13.2% 11.1% 16.3% 43.4% 38.5% 49.3%

*The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
134 MECC Monograph 

Lymphoma and Leukemia Chapter 14

highest rates in Israeli Jews (3.0), compared with a range from 1.1 

(Jordanians) to 2.2 (US SEER) (Table 14.1).

It is interesting to note the high rates of NHL in Egyptians and 

Israeli Jews. Rates of NHL have increased dramatically in Western 

Europe and North America over the past 20 years, due in part to 

AIDS. However, NHL as a complication of AIDS does not occur 

in a sufficient proportion of AIDS cases to explain the full extent 

of the increase in NHL in Western countries. Furthermore, AIDS 

rates in Egyptians and Israeli Jews are not especially high (although 

they are thought to be rising, especially in Israel). Other possible 

explanations for the higher NHL rate in Egypt may be the high 

prevalence of HCV infections [9], HHV8 infections, other types of 

infections, or adverse environmental exposures and pollution in that 

country. It should be noted that lymphoid and hematopoietic cancers 

were recognized as being relatively common in Egypt [24], even 

before the high prevalence of HCV. Several studies have reported 

the possible role of infectious agents in the etiology of NHL. 

Cowgill et al. (2004) [25] reported in an Egyptian case-control 

study a statistically significant association of HCV RNA with NHL 

(OR = 2.9; 95% CI, 1.9-4.5), after adjustment for age, sex, rural 

versus urban birthplace, and rural versus urban residence. Iscovich 

and Parkin (1997) [26] reported large differences in NHL incidence 

rates among subpopulations in Israel, with relatively high rates in 

migrants from Asia and Africa. Those high rates persisted into the 

second generation, suggesting that inherited susceptibility may 

underlie some of the variation.

Age and Sex 

Tables 14.2a, 14.2b, and 14.3 show the age and sex distribution and 

specific rates for each registry for lymphoma and leukemia over 

broad age groups. 

As seen in these tables and Table 14.1, Egyptians and Israeli Jews 

showed the highest rates of lymphoma and NHL. Also, Israeli 

Jews showed the highest ASR for HL. Table 14.4 shows that the 

5-year age patterns of NHL and HL rates differed between these 2 

registries. Egyptians had higher rates for NHL and HL in age groups 

0-14 years than did Israeli Jews. 

Contrary to the observations of higher lymphoma rates in Egyptian 

children than in Israeli Jewish children, the age-specific rate among 

Egyptians over age 75 (41.9) was less than half the rate in their 

Israeli Jewish counterparts (104.4) (Table 14.4). The low reported 

rates of lymphoma in older patients in Egypt could be due to 

cultural factors such as reluctance of older persons to seek medical 

care. It also could be due to lack of diagnostic facilities for older 

populations in peripheral regions in Egypt. 

The higher rates of lymphoma and NHL reported in Egyptians 

and Israeli Jews did not differ by sex. As shown in Table 14.5, 

lymphoma ASRs were higher for Egyptian and Israeli Jewish males, 

20.0 and 20.6, respectively, than for males in other registries. Also, 

lymphoma ASRs for females were higher in Egyptians (12.6) and 

Israeli Jews (16.9) than in other populations. NHL sex-specific rates 

were higher for Egyptian (11.3) and Israeli Jewish (13.6) females 

than for females in other registries. These data represent male-tofemale ratios of 1.6:1 for NHL in Egyptians and 1.2:1 for NHL in 

Israeli Jews. 

HL, which showed the highest rate in Israeli Jews (3.4), did not 

show a significant sex difference (3.5 in males; 3.3 in females) 

(Table 14.5).

The sex-specific rates of leukemia followed the same pattern as the 

overall rates (Table 14.1), with higher rates in US SEER and Israeli 

Jews than in the other registry populations (Table 14.5). 

Subsites

As shown in Table 14.6, extranodal NHL represented about onefourth to one-third of all NHL in the MECC registries, with the 

lowest proportion in Israeli Jews (23.2%) and the highest in Cypriots 
 MECC Monograph 135

Lymphoma and Leukemia Chapter 14

Table 14.2b. Lymphoma: Age-Standardized Incidence Rates,* by Age and Sex, for Lymphoma, Hodgkin Lymphoma, and Non-Hodgkin Lymphoma, in Cyprus, 

Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001†

Cyprus Israel (Jews) Israel (Arabs) Egypt Jordan US SEER‡

1998-2001 1996-2001 1996-2001 1999-2001 1996-2001 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Age Groups (Rates)* for Lymphoma

Total rate -- All lymphoma 10.6 12.1 9.3 18.6 20.6 16.9 12.9 14.4 11.4 16.3 20.0 12.6 8.9 10.3 7.4 15.3 18.3 12.6

<50 y 6.0 6.6 5.5 8.5 9.3 7.6 6.3 7.4 5.1 8.6 11.0 6.2 4.8 5.9 3.6 6.3 7.5 5.2

50-69 y 25.6 30.5 21.2 48.8 53.5 44.6 32.8 34.1 31.3 46.8 54.1 39.4 23.0 25.9 19.8 40.0 48.0 32.8

70+ y 42.4 49.4 36.9 100.4 113.7 90.8 65.4 76.3 56.7 48.5 64.9 34.1 35.3 37.0 33.8 95.3 117.1 80.5

Age Groups (Rates)* for Hodgkin Lymphoma

Total rate -- Hodgkin lymphoma 3.0 2.7 3.3 3.4 3.5 3.3 2.7 3.0 2.3 2.1 2.9 1.4 2.5 3.0 2.0 2.4 2.7 2.2

<50 y 3.2 3.0 3.5 3.3 3.4 3.3 2.3 2.9 1.7 2.0 2.7 1.4 2.2 2.7 1.7 2.3 2.4 2.1

50-69 y 2.5 1.9 3.0 3.5 4.1 2.9 3.8 3.9 3.7 2.9 4.3 1.6 3.5 4.1 2.9 2.7 3.3 2.0

70+ y 0.0 0.0 0.0 4.8 4.9 4.7 4.8 - 7.0 1.4 3.1 0.0 4.8 4.5 5.0 4.0 5.0 3.3

Age Groups (Rates)* for Non-Hodgkin Lymphoma

Total rate -- Non-Hodgkin lymphoma 7.6 9.4 6.0 15.2 17.1 13.6 10.2 11.4 9.1 14.2 17.1 11.3 6.4 7.3 5.4 12.9 15.7 10.5

<50 y 2.8 3.6 2.0 5.1 6.0 4.3 3.9 4.5 3.4 6.6 8.3 4.8 2.6 3.2 1.9 4.1 5.0 3.1

50-69 y 23.1 28.5 18.2 45.3 49.4 41.8 29.0 30.3 27.6 43.8 49.9 37.9 19.4 21.7 16.9 37.4 44.7 30.7

70+ y 42.4 49.4 36.9 95.6 108.8 86.1 60.7 74.3 49.7 47.1 61.8 34.1 30.5 32.5 28.8 91.3 112.1 77.2

*Rates are per 100,000 and are age-standardized to the World Standard Million.

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

(32.5%). Proportions of extranodal NHL were highest in US SEER 

(35.9%) (Table 14.6). Further analysis of the anatomical sites of 

extranodal NHL in our data showed there were no differences in 

the distribution of stomach extranodal NHL. Nevertheless, skin 

extranodal sites were higher in Israeli Jews (10.4%) and Israeli 

Arabs (10.5%) than in other MECC registries, where rates ranged 

between 1.6% and 2.2% of all extranodal lesions. The US SEER 

rate for skin NHL was 6.6%. The registry results did not support the 

previous impression of high prevalence of extranodal lymphoma 

in the small intestine previously reported in the Middle East in 

hospital-based studies [27,28]. 

HL did not vary greatly between MECC registries in relation to 

nodal and extranodal distribution (Table 14.6). Contrary to the 

large proportion of extranodal NHL (about one-third of all NHL 

tumors), extranodal HL represented no more than 5.3% of all HL. 

Hodgkin extranodal tumors represented 2.3% of Hodgkin tumors in 

the United States. Further analysis showed there was no major sex 

difference. 
136 MECC Monograph 

Lymphoma and Leukemia Chapter 14

Table 14.3. Leukemia: Number of Cases, Age Distribution, and Age-Standardized Incidence Rates, by Age and Sex, in Cyprus, Israel (Jews 

and Arabs), Egypt, Jordan, and US SEER – 1996-2001*

Cyprus Israel (Jews) Israel (Arabs) Egypt Jordan US SEER†

1998-2001 1996-2001 1996-2001 1999-2001 1996-2001 1999-2001

Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

Total cases 223 134 89 3,220 1,790 1,430 325 192 133 515 283 232 1,354 782 572 13,178 7,528 5,650

Age Groups (Distribution)

<40 y 27.4% 25.4% 30.3% 17.1% 18.1% 15.9% 51.4% 51.6% 51.1% 50.9% 51.6% 50.0% 59.5% 60.0% 58.9% 18.9% 18.7% 19.3%

40-59 y 25.1% 26.9% 22.5% 18.1% 19.7% 16.2% 23.4% 24.5% 21.8% 29.3% 25.1% 34.5% 20.6% 18.7% 23.3% 19.7% 20.5% 18.6%

60-69 y 19.7% 23.1% 14.6% 19.8% 19.9% 19.6% 9.5% 9.4% 9.8% 14.0% 16.3% 11.2% 12.3% 13.2% 11.2% 16.0% 17.6% 13.9%

70+ y 27.8% 24.6% 32.6% 45.0% 42.3% 48.3% 15.7% 14.6% 17.3% 5.8% 7.1% 4.3% 7.5% 8.2% 6.6% 45.3% 43.2% 48.1%

Age Groups (Rates) ‡

Total rate 6.9 8.5 5.5 8.6 10.5 6.9 6.4 7.8 5.1 6.0 6.7 5.3 6.3 7.1 5.5 8.8 11.0 6.9

<40 y 3.9 4.2 3.7 3.1 3.5 2.6 2.9 3.4 2.4 3.3 3.6 3.0 3.4 3.7 3.0 3.8 4.2 3.5

40-59 y 8.0 10.4 5.7 9.5 11.9 7.3 8.6 10.6 6.5 9.2 8.6 9.8 8.3 8.4 8.2 8.7 10.6 6.9

60-69 y 20.3 30.2 11.6 30.7 38.1 24.6 15.2 19.2 11.9 17.2 22.4 12.2 20.1 23.2 16.5 27.7 37.1 19.4

70+ y 28.4 32.7 25.2 59.3 74.3 48.6 38.4 47.9 31.1 14.4 20.9 8.7 21.4 28.3 15.1 59.5 83.6 43.4

*[Numeral]” (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

‡Rates are per 100,000 and are age-standardized to the World Standard Million.

CLL, which in the new classification is counted as a type of 

lymphoma, showed high rates (3.0) in Israeli Jews, with higher rates 

in males (3.8, compared with 2.3 in females), and a male-to-female 

ratio of 1.7:1. Rates of CLL ranged in other MECC registries and US 

SEER from 1.1 to 2.2, with male-to-female ratios ranging between 

1.25:1 and 2.2:1 (Table 14.5).

Basis of Diagnosis

Histopathological diagnostic rates were over 90% for most types 

of lymphomas and leukemias (see Table 1.2). However, it should 

be noted that available diagnostic facilities might not be available 

at peripheral remote medical centers, and patients may die before 

reaching cancer centers for correct diagnosis and management. This 

may be the case for myeloma in Egypt, where a pathologic diagnosis 

was observed for 100% of cases. The low incidence of myeloma and 

NHL in the older population in Egypt, and possibly other MECC 

registries, might be due to misdiagnosis or short life expectancy. It 

is difficult to know how much the age structure of the population 

and local factors in each country might influence access to medical 

care and interfere with the diagnostic facilities for diagnosis and 

management of hematopoietic malignancies. 
 MECC Monograph 137

Lymphoma and Leukemia Chapter 14

Table 14.4. Lymphoma: Age-Specific Incidence Rates* of Non-Hodgkin Lymphoma and Hodgkin 

Lymphoma, by Age and Sex, in Israel (Jews) and Egypt – 1996-2001†

Non-Hodgkin Lymphoma Hodgkin Lymphoma

Israel (Jews) Egypt Israel (Jews) Egypt

1996-2001 1999-2001 1996-2001 1999-2001

Age Group Total Male Female Total Male Female Total Male Female Total Male Female

0-4 y 1.0 1.1 0.8 2.6 3.6 1.5 0.2 0.4 - 0.6 0.7 -

5-9 y 1.6 2.3 0.8 2.3 3.2 1.3 0.8 1.4 0.2 2.3 4.0 0.5

10-14 y 1.0 1.4 0.6 1.9 3.1 0.6 1.6 1.6 1.5 1.7 2.4 1.0

15-19 y 2.1 2.2 2.0 1.6 2.0 1.1 6.0 5.5 6.5 1.9 2.7 1.1

20-24 y 3.4 3.2 3.7 4.1 3.8 4.5 6.1 5.7 6.6 2.7 2.5 2.9

25-29 y 4.1 4.7 3.6 4.6 7.2 2.3 6.9 5.8 8.0 1.8 2.8 1.0

30-34 y 7.5 8.4 6.6 7.8 10.7 4.9 4.5 4.2 4.8 1.2 1.6 0.8

35-39 y 8.7 11.0 6.6 10.8 13.7 8.0 3.9 4.1 3.6 1.5 2.0 1.1

40-44 y 13.9 16.2 11.7 16.4 22.0 10.6 3.3 4.3 2.3 3.2 5.3 1.0

45-49 y 18.8 22.2 15.7 26.9 29.4 24.0 2.4 3.0 1.8 4.6 3.8 5.5

50-54 y 30.0 30.9 29.2 37.7 36.7 38.6 3.5 4.1 3.0 3.3 6.1 -

55-59 y 39.8 46.6 33.6 39.7 48.4 30.5 2.7 3.4 2.2 3.0 4.3 -

60-64 y 51.9 54.7 49.5 50.6 59.6 42.5 4.1 4.3 4.0 2.0 - 2.3

65-69 y 69.4 77.0 63.4 50.6 60.8 40.4 3.4 5.1 2.0 3.5 4.6 -

70-74 y 86.9 98.2 78.4 52.3 70.8 35.7 6.3 6.2 6.4 - - 0.0

75+ y 104.4 119.5 93.8 41.9 52.8 32.5 3.3 3.6 3.1 - - 0.0

*Rates are per 100,000..

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

SUMMARY AND CONCLUSIONS

Analysis of the MECC registries yields the following interesting 

observations: (1) Lymphoma and NHL incidence rates in Egyptians 

and Israeli Jews were high; (2) NHL incidence rates in older 

Egyptians were relatively low, which could be due to lack of access 

to medical care in peripheral regions or short life expectancy; and 

(3) the high rate of CLL in Israeli Jews could be a component of the 

high lymphoma rate in that population. 

Geographic variations in incidence and age distribution of NHL 

might be a reflection of local environmental factors implicated in the 

etiology of the disease. Based on the different ethnicities, lifestyles, 

socioeconomic levels, and adverse environmental exposures among 

the countries of the Middle East, comparison of populations can 

provide the background for more sophisticated approaches for 

disentangling the risk factors for lymphoid and hematopoietic 

malignancies. Further exploration of potential etiologic risk factors 

should be the focus of future epidemiologic research. 
138 MECC Monograph 

Lymphoma and Leukemia Chapter 14

Table 14.5. Lymphoma and Leukemia: Age-Standardized Incidence Rates, by Sex, in 

Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001*

Cyprus

 1998-2001

Israel (Jews) 

1996-2001

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER†

 1999-2001

Lymphoma

Total rate 10.6 18.6 12.9 16.3 8.9 15.3

Male 12.1 20.6 14.4 20.0 10.3 18.3

Female 9.3 16.9 11.4 12.6 7.4 12.6

Non-Hodgkin Lymphoma

Total rate 7.6 15.2 10.2 14.2 6.4 12.9

Male 9.4 17.1 11.4 17.1 7.3 15.7

Female 6.0 13.6 9.1 11.3 5.4 10.5

Hodgkin Lymphoma 

Total rate 3.0 3.4 2.7 2.1 2.5 2.4

Male 2.7 3.5 3.0 2.9 3.0 2.7

Female 3.3 3.3 2.3 1.4 2.0 2.2

Leukemia

Total rate 6.9 8.6 6.4 6.0 6.3 8.8

Male 8.5 10.5 7.8 6.7 7.1 11.0

Female 5.5 6.9 5.1 5.3 5.5 6.9

Chronic Lymphocytic Leukemia

Total rate 1.8 3.0 1.3 1.3 1.1 2.2

Male 2.4 3.8 1.5 1.7 1.3 3.1

Female 1.2 2.3 1.2 0.9 0.8 1.4

*Rates are per 100,000 and are age-standardized to the World Standard Million.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
 MECC Monograph 139

Lymphoma and Leukemia Chapter 14

REFERENCES

[1] Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994;84:1361-

92.

[2] Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization classification of tumors. Pathology and genetics of tumors of 

hematopoietic and lymphoid tissues. Lyon (France): International Agency 

for Research on Cancer; 2001.

[3] Bain BJ. Routine and specialised techniques in the diagnosis of haematological neoplasms. J Clin Pathol 1995;48:501-8.

[4] Stewart BW, Kleihues P, editors. World cancer report. Lyon (France): 

International Agency for Research on Cancer; 2003.

[5] International Agency for Research on Cancer. IARC monographs on the 

evaluation of carcinogenic risks to humans, vol. 67. Human immunodeficiency viruses and human T-cell lymphotropic viruses. Lyon (France): 

International Agency for Research on Cancer; 1996.

[6] Baecklund E, Sundstrom C, Ekbom A, Catrina AI, Biberfeld P, Feltelius N, et al. Lymphoma subtypes in patients with rheumatoid arthritis: 

increased proportion of diffuse large B cell lymphoma. Arthritis Rheum 

2003;48:1543-50.

[7] Palacios E, Larusso G, Rojas R, Ramirez G. Lymphoma of the parotid 

gland in Sjogren’s syndrome. Ear Nose Throat J 2004;83:156.

[8] Smedby KE, Akerman M, Hildebrand H, Glimelius B, Ekbom A, Askling 

J. Malignant lymphomas in coeliac disease: evidence of increased risks 

for lymphoma types other than enteropathy-type T cell lymphoma. Gut 

2005;54:54-9.

[9] Mueller NE, Mohar A, Evans A. Viruses other than HIV and non-Hodgkin’s lymphoma. Cancer Res 1992;52:5479s-81s.

[10] Nagore E, Ledesma E, Collado C, Oliver V, Perez-Perez A, Aliaga A. 

Detection of Epstein-Barr virus and human herpesvirus 7 and 8 genomes in primary cutaneous T- and B-cell lymphomas. Br J Dermatol 

2000;143:320-3.

[11] Killebrew D, Shiramizu B. Pathogenesis of HIV-associated non-Hodgkin 

lymphoma. Curr HIV Res 2004;2:215-21.

Table 14.6. Lymphoma: Distribution of Non-Hodgkin Lymphoma and Hodgkin Lymphoma, by Nodal and 

Extranodal Status, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001*

Cyprus

 1998-2001

Israel (Jews)

 1996-2001

Israel (Arabs)

 1996-2001

Egypt

 1999-2001

Jordan

 1996-2001

US SEER†

 1999-2001

Non-Hodgkin lymphoma 

– Nodal 67.5% 76.8% 75.3% 70.5% 74.1% 64.1%

Non-Hodgkin lymphoma 

– Extranodal 32.5% 23.2% 24.7% 29.5% 25.9% 35.9%

Hodgkin lymphoma – Nodal 95.2% 98.4% 97.6% 96.3% 94.7% 97.7%

Hodgkin lymphoma 

– Extranodal 4.8% 1.6% 2.4% 3.7% 5.3% 2.3%

*[Numeral] (italic) = 0 or 3-15 cases.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
140 MECC Monograph 

Lymphoma and Leukemia Chapter 14

[12] Turner NC, Dusheiko G, Jones A. Hepatitis C and B-cell lymphoma. Ann 

Oncol 2003;14:1341-5.

[13] Matsuo K, Kusano A, Sugumar A, Nakamura S, Tajima K, Mueller NE. 

Effect of hepatitis C virus infection on the risk of non-Hodgkin’s lymphoma: a meta-analysis of epidemiological studies. Cancer Sci 2004;95:745-

52.

[14] Luppi M, Barozzi P, Maiorana A, Artusi T, Trovato R, Marasca R, et al. 

Human herpesvirus-8 DNA sequences in human immunodeficiency virusnegative angioimmunoblastic lymphadenopathy and benign lymphadenopathy with giant germinal center hyperplasia and increased vascularity. 

Blood 1996;87:3903-9.

[15] Blattner WA. Human retroviruses: their role in cancer. Proc Assoc Am 

Physicians 1999;111:563-72.

[16] Knowles DM. Immunodeficiency-associated lymphoproliferative disorders. Mod Pathol 1999;12:200-17.

[17] Bechtel D, Kurth J, Unkel C, Kuppers R. Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in 

the pathogenesis of Hodgkin and posttransplantation lymphomas. Blood 

2005;106:4345-50.

[18] Crowe SE. Helicobacter infection, chronic inflammation, and the development of malignancy. Curr Opin Gastroenterol 2005;21:32-8.

[19] AIDS.ORG. Lymphoma. 8-12-2004. Available at: http://www.aids.org/

factSheets/512-Lymphoma.html. [Last Accessed: 1/06].

[20] Levine AM. AIDS-related malignancies: the emerging epidemic. J Natl 

Cancer Inst 1993;85:1382-97.

[21] Pallesen G, Hamilton-Dutoit SJ, Zhou X. The association of Epstein-Barr 

virus (EBV) with T cell lymphoproliferations and Hodgkin’s disease: two 

new developments in the EBV field. Adv Cancer Res 1993;62:179-239.

[22] Adegoke OJ, Blair A, Shu XO, Sanderson M, Jin F, Dosemeci M, et 

al. Occupational history and exposure and the risk of adult leukemia in 

Shanghai. Ann Epidemiol 2003;13:485-94.

[23] Parkin DM, Ferlay M, Hamdi-Cherif M, Sitas F, Thomas J, Wabinga H, 

et al. Cancer in Africa: epidemiology and prevention. IARC scientific 

publication no. 153. Lyon (France): International Agency for Research on 

Cancer; 2003.

[24] Mokhtar A, editor. Cancer Pathology Registry (1985-1989). Cairo 

(Egypt): Cairo National Cancer Institute; 2001.

[25] Cowgill KD, Loffredo CA, Eissa SA, Mokhtar N, Abdel-Hamid M, Fahmy A, et al. Case-control study of non-Hodgkin’s lymphoma and hepatitis 

C virus infection in Egypt. Int J Epidemiol 2004;33:1034-9.

[26] Iscovich J, Parkin DM. Risk of cancer in migrants and their descendants 

in Israel: I. Leukaemias and lymphomas. Int J Cancer 1997;70:649-53.

[27] Isaacson PG. Middle Eastern intestinal lymphoma. Semin Diagn Pathol 

1985;2:210-23.

[28] Salem P, el Hashimi L, Anaissie E, Geha S, Habboubi N, Ibrahim N, et 

al. Primary small intestinal lymphoma in adults. A comparative study of 

IPSID versus non-IPSID in the Middle East. Cancer 1987;59:1670-6.
 MECC Monograph 141

Childhood Cancer Chapter 15

AYHAN O. ÇAVDAR, TEZER KUTLUK

BACKGROUND

There are marked differences between childhood and adult cancer. 

First, cancer is generally a rare disease among children. Annual 

incidence of all cancer in children under 5 years of age in developed 

countries is only 0.5%, according to a new report [1]. In European 

countries, 1% of all malignant neoplasms occur in patients 

younger than 20 years of age [2-4]. Second, childhood cancers are 

histologically variable, and embryonic tumors are the most common, 

while the majority of adult cancers are carcinomas [1,5,6]. Twelve 

types of malignant childhood tumors have been classified according 

to the International Classification of Childhood Cancer (ICCC) [1,7-

10]; however, pediatric cancers can also be divided into 3 subgroups 

[6]:

1. Embryonal tumors, which show early age peaks. Retinoblastoma, 

neuroblastoma, and hepatoblastoma have the highest incidence rate 

in the first year of life. 

2. Juvenile neoplasms, which are unique to younger age groups.

3. Adult-type tumors, which are rarely seen in children. 

Prenatal factors are considered to affect the incidence of tumors 

in children under the age of 5 years [11]. It is generally accepted 

that cancer results from genetic changes [1,12]. The carcinogenic 

process in children is much shorter than in adults. Infancy is the 

age when cancer incidence rates are the highest during childhood; 

therefore, it is reasonable to assume that many pediatric cancers 

result from aberrations in early developmental stages and in utero. 

An increased risk of childhood cancers has been described to be 

associated with certain genetic conditions or syndromes such as 

chromosomal abnormalities, DNA repair disorders, congenital 

anomalies, hereditary immune deficiency states, and other hereditary 

syndromes [1,6]. 

Racial differences have been observed in childhood tumors, 

even within Western countries [2,12]. A peak incidence in acute 

lymphocytic leukemia (ALL) usually occurs between the ages of 2 

and 3 years in White American children and 1 to 4 years in European 

children, but not among African Americans [1,2]. Ewing sarcoma 

is another well-established example of racial differences, with the 

lowest incidence rate in Black children (African or American) [1,6]. 

Furthermore, there are marked variations between populations in the 

incidence of specific types of childhood cancers. Nearly one-third 

of all childhood neoplasms are leukemias, with an age-standardized 

incidence rate (ASR) of 35-50 per million [1,7]. International 

variation occurs in the rate of ALL, and the higher incidence of 

ALL in early childhood has usually been associated with higher 

levels of socioeconomic status. This suggests that environmental 

factors play a role [1,9,13]. Although a considerable number of 

environmental or exogenous factors have been suggested as risk 

factors for childhood cancers, only a few have been proven, and they 

are mostly infectious agents, including Epstein-Barr virus, hepatitis 

B virus, human immunodeficiency virus, and human herpesvirus 

8. These infections are probably responsible for the international 

variation in the incidence of some childhood cancers, such as 

lymphoma, nasopharyngeal carcinoma, hepatic cancer, and Kaposi 

sarcoma [1,6,13,14]. In addition, some parasitic infections have 

been implicated, particularly malaria in tropical Africa, acting as 

a co-factor for Burkitt’s lymphoma, and schistosomiasis in Egypt, 

causing bladder cancer [1,11,15]. 
142 MECC Monograph 

Childhood Cancer Chapter 15

RESULTS

The total number of childhood cancers registered under 15 years 

of age varies greatly among the Middle East Cancer Consortium 

(MECC) registries, ranging from 102 in Cyprus to 1,339 in Jordan 

(Table 15.1). This is due both to different periods of registration 

in these countries and to variations in the size of their respective 

populations.

Table 15.2 shows the ASRs of all cancers and the main types of 

cancer, and Figure 15.1 shows the ASRs of all cancers, by sex, in 

children under 15 years of age in MECC countries. The most striking 

finding is that the highest incidence of childhood cancer occurred 

among female children in Cyprus (179.5). This rate was even higher 

than that found among females in the SEER data (146.3). Males had 

a higher incidence rate than females in all other MECC countries 

(ranging from 130.6 to 150.3). The lowest overall incidence was in 

Jordan (114.8). 

In terms of the type of malignancy, leukemia was the most common 

neoplasm in males in all MECC countries, with the exception 

of Egypt, where lymphoma in males exceeded the incidence of 

leukemia (56.7 vs. 33.6) (Table 15.2; Figures 15.2 and 15.3). The 

second highest lymphoma rate was in Israeli Arabs, with an ASR 

of 32.6 in males (Table 15.2 and Figure 15.3). The incidence rate 

of ALL was 38.2, 21.4, 15.9, 24.3, 27.8, and 39.7 in Cypriots, 

Israeli Jews, Israeli Arabs, Egyptians, Jordanians, and US SEER, 

respectively, whereas it was 12.7, 5.5, 6.4, 3.1, 5.7, and 7.3 for 

acute myeloid leukemia in the same countries. Interestingly, the 

rate of central nervous system (CNS) tumors was found to be the 

highest in females (55.6) in Cyprus (Table 15.2 and Figure 15.4). 

Although lymphomas were more common than CNS tumors in male 

Israeli Jews, male and female Israeli Arabs, male Egyptians, and 

male Jordanians, the opposite was true for the rest of the registries.

Sympathetic nervous system tumors were also higher in Cyprus 

than in the other MECC countries and the US SEER population, 

particularly in males (28.4). Jordan had the lowest incidence 

of sympathetic nervous system tumors. It is of interest that no 

retinoblastoma was diagnosed in Cyprus, even in the under-5-years 

age group. As far as renal tumors were concerned, incidence rates 

were again the highest in Cypriot children, particularly in females 

(14.6), compared with the other MECC countries (Table 15.2).

Table 15.1. Childhood Cancer: Number of Cases for All International Classification of Childhood Cancer Sites, by Age and Sex, in Cyprus, 

Israel (Jews and Arabs), Egypt, Jordan, and US SEER − 1996-2001

Cyprus Israel (Jews) Israel (Arabs) Egypt Jordan US SEER*

1998-2001 1996-2001 1996-2001 1999-2001 1996-2001 1999-2001

Age Group Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

<5 y 41 19 22 404 220 184 170 98 72 157 86 71 557 336 221 1,699 898 801

5-9 y 27 14 13 291 183 108 93 60 33 156 100 56 404 229 175 1,013 583 430

10-14 y 34 17 17 303 175 128 74 41 33 168 99 69 378 217 161 1,096 553 543

15-19 y 47 18 29 554 287 267 106 54 52 185 104 81 462 244 218 1,644 882 762

<15 y 102 50 52 998 578 420 337 199 138 481 285 196 1,339 782 557 3,808 2,034 1,774

<20 y 149 68 81 1,552 865 687 443 253 190 666 389 277 1,801 1,026 775 5,452 2,916 2,536

*SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
 MECC Monograph 143

Childhood Cancer Chapter 15

The total incidence of hepatic tumors ranged from 2.5 in Israeli 

Arabs to 1.1 in Jordanians (Table 15.2). 

The incidence of malignant bone tumors was slightly higher in 

Cypriot males (10.2) and Israeli Jewish males (9.5) as well as in 

female Egyptians (9.3), compared with other MECC countries. 

Interestingly, these tumors had the lowest ASR in Israeli Arabs, 

although it was found to be high (8.6) among Egyptian children 

(Table 15.2). 

Soft tissue sarcomas showed a slightly higher ASR among Israeli 

Arabs, particularly in females (14.7) and in male Israeli Jews (12.8) 

(Table 15.2).

Table 15.2. Childhood Cancer: Age-Standardized Incidence Rates* for International Classification of Childhood Cancer (ICCC) Sites, by Sex, in Children 

under Age 15 Years in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001†

Cyprus Israel (Jews) Israel (Arabs) Egypt Jordan US SEER‡

1998-2001 1996-2001 1996-2001 1999-2001 1996-2001 1999-2001

ICCC Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

All cancers 170.0 161.0 179.5 133.3 150.0 115.8 119.9 137.8 100.9 130.9 150.3 110.7 114.8 130.6 98.1 153.3 159.9 146.3

Leukemia 53.0 52.8 53.2 31.8 34.7 28.7 29.4 33.8 24.8 31.9 33.6 30.2 39.2 46.5 31.4 50.4 54.0 46.6

Lymphomas and

reticuloendothelial neoplasms 15.7 20.1 11.2 20.0 26.5 13.1 24.2 32.6 15.4 37.7 56.7 17.7 19.0 23.8 13.9 13.5 16.3 10.5

Central nervous system and 

miscellaneous intracranial and 

intraspinal neoplasms 40.1 25.3 55.6 24.2 25.9 22.4 16.5 22.7 10.1 16.9 15.7 18.1 18.9 21.5 16.2 32.5 34.6 30.3

Sympathetic nervous system 

tumors 22.3 28.4 15.8 15.8 16 15.5 12.0 12.4 11.7 9.5 11.8 7.0 6.1 7.0 5.2 11.2 10.3 12.1

Retinoblastoma 0.0 0.0 0.0 2.8 2.3 3.3 2.1 2.0 2.2 2.4 - 3.5 4.6 4.4 4.9 5.6 6.6 4.6

Renal tumors 11.3 - 14.6 6.9 8.4 5.3 5.7 4.1 7.3 5.4 4.4 6.4 5.1 4.4 5.8 9.2 8.0 10.3

Hepatic tumors - - 0.0 1.3 2.2 - 2.5 2.1 2.9 1.9 1.9 2.0 1.1 1.2 0.9 2.9 2.5 3.3

Malignant bone tumors 7.9 10.2 - 8.1 9.5 6.7 3.3 4.3 2.3 8.6 8.0 9.3 6.0 7.3 4.7 5.2 5.3 5.1

Soft tissue sarcomas 9.8 12.1 - 11.0 12.8 9.1 13.6 12.5 14.7 7.9 9.0 6.7 6.3 7.3 5.2 10.8 11.7 9.9

Germ cell, trophoblastic, and 

other gonadal neoplasms - 0.0 - 3.1 1.5 4.7 3.6 2.8 4.4 2.2 1.8 2.6 3.4 2.7 4.3 5.3 5.4 5.2

Carcinomas and other

malignant epithelial neoplasms 3.9 0.0 8.1 5.6 6.7 4.4 4.3 5.7 2.9 2.4 2.5 2.2 4.3 3.9 4.6 5.7 4.4 7.0

Other and unspecified 

malignant neoplasms 0.0 0.0 0.0 1.9 2.1 1.6 2.2 2.1 2.2 3.9 3.3 4.5 0.7 0.7 0.8 0.5 0.3 0.6

Not classified by ICCC - 0.0 - 1.0 1.3 - - - 0.0 - 0.0 - - 0.0 - 0.7 0.5 0.8

*Rates are per 1,000,000 and are age-standardized to the World Standard Million.

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
144 MECC Monograph 

Childhood Cancer Chapter 15

170

133

120

131

115

153

161

150

138

150

131

160

179

116

101

111

98

146

0 50 100 150 200

Cyprus

Israel (Jews)

Israel (Arabs)

Egypt

Jordan 

US SEER† 

Incidence Rates per Million

Total

Male

Female

Figure 15.1. Childhood Cancer: Age-Standardized Incidence Rates* of All Cancers for Children 

under Age 15 Years, by Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER –

1996-2001

*Rates are per 1,000,000 and are age-standardized to the World Standard Million.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

The incidence of germ cell tumors was slightly lower in all MECC 

countries than in US SEER data, with the lowest total ASR of 2.2 

noted in Egypt versus 5.3 in US SEER. In Cyprus, there were only 2 

cases, so the ASR could not be properly estimated.

The incidence rate of carcinomas and other malignant epithelial 

neoplasms was low in all MECC countries. Interestingly, no cases 

were registered in male Cypriots, whereas female Cypriots (8.1) and 

male Israeli Jews (6.7) had slightly higher rates (Table 15.2).

Other and unspecified malignant neoplasms were generally low 

in MECC countries. No such cases were reported from Cyprus 

(Table 15.2). 

Table 15.3 shows the incidence rates according to the ICCC site 

for children under 20 years of age. The total ASR of malignant 

tumors was again highest in Cyprus (178.6), and was also 

relatively high among Israeli Jews (154.2). 

Table 15.4 shows the ASRs of all malignant neoplasms in 5-

year age groups for males and females. In Cyprus, the incidence 

53

32

29

32

39

50

53

35

34

34

46

54

53

29

25

30

31

47

0 10 20 30 40 50 60

Cyprus

Israel (Jews)

Israel (Arabs)

Egypt

Jordan 

US SEER† 

Incidence Rates per Million

Total

Male

Female

Figure 15.2. Childhood Cancer: Age-Standardized Incidence Rates* of Leukemia for Children under 

Age 15 Years, by Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan and US SEER – 1996-2001

*Rates are per 1,000,000 and are age-standardized to the World Standard Million.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
 MECC Monograph 145

Childhood Cancer Chapter 15

rates of cancers under 5 years (199.2 in males; 241.8 in females) 

seemed again higher than in the other MECC countries and similar 

to the US SEER rates (210.4 and 196.9, respectively). The highest 

incidence rates in adolescents were in female Cypriots (262.0) and 

male and female Israeli Jews (226.2) (Table 15.4).

Comparing Other Childhood Cancer Registries with MECC 

Comparison of the rates reported by cancer registries in some 

European countries [2-4] with those of MECC countries is shown 

in Table 15.5. Analysis of the total ASRs of childhood cancer 

in MECC and European countries revealed the highest rates in 

Cyprus (170.0) and Italy (158.0). These 2 countries had almost the 

same incidence rate of leukemia (53.0 and 53.9, respectively). With 

the exception of Cyprus (53.0), MECC registries in general tended 

to have a lower incidence rate of leukemia (29.4 to 39.2) than in 

the European countries, where incidence of leukemia varied from 

41.0 to 53.9 [3]. In a previous study, the frequency of T-cell ALL 

was found to be high in Egypt [16]. Childhood leukemia rates were 

found to be higher in Jordanians than in Israeli Jews, according to a 

recent report [17].

According to Table 15.5, the incidence of lymphoma tended 

to be higher in the MECC countries than in Europe, but Spain 

and Italy had a relatively high rate of this malignancy (19.3 and 

18.6, respectively). The highest rate of lymphoma within MECC 

16

20

24

38

19

14

20

27

33

57

24

16

11

13

15

18

14

10

0 10 20 30 40 50 60

Cyprus

Israel (Jews)

Israel (Arabs)

Egypt

Jordan 

US SEER† 

Incidence Rates per Million

Total

Male

Female

Figure 15.3. Childhood Cancer: Age-Standardized Incidence Rates* of Lymphoma and Reticuloendothelial

Neoplasms for Children under Age 15 Years, by Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US 

SEER – 1996-2001 

*Rates are per 1,000,000 and are age-standardized to the World Standard Million.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.

40

24

17

17

19

32

25

26

23

16

21

35

56

22

10

18

16

30

0 10 20 30 40 50 60

Cyprus

Israel (Jews)

Israel (Arabs)

Egypt

Jordan 

US SEER† 

Incidence Rates per Million

Total

Male

Female

Figure 15.4. Childhood Cancer: Age-Standardized Incidence Rates* of Malignant Central Nervous System and 

Miscellaneous Intracranial and Intraspinal Neoplasms for Children under Age 15 Years, by Sex, in Cyprus, 

Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001

*Rates are per 1,000,000 and are age-standardized to the World Standard Million.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
146 MECC Monograph 

Childhood Cancer Chapter 15

Table 15.3. Childhood Cancer: Age-Standardized Incidence Rates* for International Classification of Childhood Cancer (ICCC) Sites, by Sex, in Children 

under Age 20 Years in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001† 

Cyprus Israel (Jews) Israel (Arabs) Egypt Jordan US SEER‡

1998-2001 1996-2001 1996-2001 1999-2001 1996-2001 1999-2001

ICCC Site Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

All cancers 178.6 160.0 198.1 154.2 167.6 140.1 126.9 140.7 112.4 134.8 153.1 115.6 119.7 132.4 106.4 164.0 171.0 156.5

Leukemia 49.1 46.8 51.4 30.2 34.1 26.2 27.3 30.6 23.8 32.1 35.2 28.9 36.5 43.1 29.5 45.4 48.5 42.2

Lymphomas and

reticuloendothelial neoplasms 26.2 23.4 29.0 33.7 37.7 29.4 29.7 37.8 21.1 37.3 54.5 19.3 23.1 26.0 20.1 20.3 22.5 18.0

Central nervous system and

miscellaneous intracranial and 

intraspinal neoplasms 34.1 25.5 43.1 21.5 22.4 20.6 17.0 22.0 11.8 15.2 15.0 15.5 18.7 21.6 15.6 29.3 32.0 26.3

Sympathetic nervous system 

tumors 17.2 22.0 12.3 12.6 12.6 12.6 9.7 10.2 9.1 7.5 9.2 5.8 5.0 5.6 4.3 8.8 8.2 9.5

Retinoblastoma 0.0 0.0 0.0 2.2 1.8 2.6 1.6 1.6 1.7 1.9 - 2.7 3.6 3.4 3.8 4.4 5.1 3.6

Renal tumors 8.7 - 11.3 5.4 6.7 4.1 4.4 3.2 5.6 4.2 3.4 5.0 4.1 3.5 4.7 7.4 6.6 8.2

Hepatic tumors - - 0.0 1.1 1.7 - 2.2 1.6 2.9 1.9 1.8 1.9 0.9 1.1 0.7 2.5 2.2 2.9

Malignant bone tumors 14.1 19.7 8.3 10.6 13.8 7.3 5.2 5.9 4.4 10.6 11.1 10.1 8.7 10.0 7.2 6.9 8.1 5.6

Soft tissue sarcomas 8.6 11.3 - 12.8 13.7 11.9 14.7 13.5 16.0 9.7 9.1 10.4 6.1 6.7 5.5 12.4 13.6 11.0

Germ cell, trophoblastic, and other 

gonadal neoplasms 5.0 - 8.3 6.6 7.6 5.6 3.4 2.8 4.1 2.6 1.8 3.5 4.5 3.5 5.5 11.2 13.6 8.6

Carcinomas and other malignant 

epithelial neoplasms 13.0 0.0 26.6 14.3 12.4 16.3 8.8 8.1 9.5 6.9 6.5 7.3 7.9 7.4 8.5 14.2 9.7 18.9

Other and unspecified

malignant neoplasms 0.0 0.0 0.0 2.2 2.0 2.3 2.6 2.9 2.4 4.6 4.3 5.0 0.6 0.5 0.7 0.6 0.4 0.8

Not classified by ICCC - 0.0 - 1.0 1.2 0.9 - - 0.0 - 0.0 - - - - 0.6 0.5 0.7

*Rates are per 1,000,000 and are age-standardized to the World Standard Million.

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

‡SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
 MECC Monograph 147

Childhood Cancer Chapter 15

countries was in Egyptians (37.7), followed by Israeli Arabs 

(24.2). The recently established cancer registry in Turkey has also 

revealed a high incidence rate of lymphomas (19.6) among Turkish 

children [18,19]. 

CNS tumor rates were somewhat low in MECC countries (with 

the exception of 40.1 in Cyprus) as compared with European 

countries, where the highest rate of 42.8 was found in Sweden 

[19]. 

Table 15.5 shows that within MECC countries, the highest rate of 

neuroblastoma occurred in Cypriots (22.3); the rate was also high 

in Israeli Jews (15.8). In Europe, France and Italy showed high 

rates of this tumor (13.5 and 13.4, respectively). The incidence 

of retinoblastoma was low in general within MECC countries. 

Slightly higher incidence rates, ranging from 3.4 to 4.8, were 

found in Europe. Renal tumors again had the highest rate in 

Cyprus (11.3) within MECC countries, an ASR similar to 

that found in Sweden (10.2). The incidence of hepatic tumors 

in MECC registries was not grossly different from that in 

European countries; both showed low rates. The incidence rates 

of bone tumors were the highest in Egyptians (8.6), followed 

by Israeli Jews (8.1) and Cypriots (7.9). Among European 

countries, Spain (7.6) and Italy (7.5) had the highest rates.

Soft tissue sarcoma was most common in Israeli Arabs (13.6), 

whereas Sweden had the highest rate (10.5) among European 

countries. Germ cell tumors were lowest in Egypt and Cyprus 

within the MECC countries (Table 15.5). 

Table 15.4. Childhood Cancer: Age-Standardized Incidence Rates* for all International Classification of Childhood Cancer Sites, by Age and 

Sex, in Cyprus, Israel (Jews and Arabs), Egypt, Jordan, and US SEER – 1996-2001

Cyprus Israel (Jews) Israel (Arabs) Egypt Jordan US SEER†

1998-2001 1996-2001 1996-2001 1999-2001 1996-2001 1999-2001

Age Group Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female Total Male Female

<5 y 220.0 199.2 241.8 155.9 165.3 145.9 155.3 174.4 135.1 145.9 156.2 135.1 132.2 155.0 108.0 203.8 210.4 196.9

5-9 y 124.4 125.3 123.3 117.5 144.3 89.5 99.1 124.7 72.2 122.6 153.7 90.1 102.9 113.5 91.8 115.1 129.4 100.1

10-14 y 154.1 149.6 158.9 120.8 136.0 104.9 95.7 103.7 87.3 120.2 138.6 100.9 104.8 116.9 92.0 128.3 126.4 130.3

15-19 y 208.3 156.7 262.0 226.2 228.3 224.0 151.1 150.5 151.8 148.1 162.6 132.8 136.8 138.6 134.8 200.8 209.3 191.8

<15 y 170.0 161.0 179.5 133.3 150.0 115.8 119.9 137.8 100.9 130.9 150.3 110.7 114.8 130.6 98.1 153.3 159.9 146.3

<20 y 178.6 160.0 198.1 154.2 167.6 140.1 126.9 140.7 112.4 134.8 153.1 115.6 119.7 132.4 106.4 164.0 171.0 156.5

*Rates are per 1,000,000, and rates for the broad age groups are age-standardized to the World Standard Million.

†SEER 13 Registries, Public Use Data Set, from data submitted November 2004.
148 MECC Monograph 

Childhood Cancer Chapter 15

Interestingly, the total ASR of childhood tumors in Turkey (Izmir 

registry), 115.6, was quite low and similar to the rate (114.8) in 

Jordan (Table 15.5).

SUMMARY AND CONCLUSIONS 

The results of this analysis of MECC registries may be 

summarized as follows:

1. Among MECC countries, the total incidence of childhood 

tumors was highest in Cyprus (170.0).

2. Leukemia was the most common childhood malignancy in 

all MECC countries, with the exception of Egypt. However, 

the MECC ASR of leukemia was somewhat low compared with 

the European countries. The incidence of ALL was highest in 

Cyprus. 

3. The total ASR of lymphoma in Egypt (37.7) exceeded 

leukemia (31.9), with a very high rate among male children 

(56.7). Male Israeli Arabs also had a high rate of lymphoma. 

The incidence of lymphoma in MECC countries was generally 

high, compared with Europe (14.3) and the US SEER population 

(13.5). 

Table 15.5. Childhood Cancer: Comparison of Age-Standardized Incidence Rates* in MECC Countries, Some European Countries, and 

US SEER†‡

Country/Registry Total Rate Leukemia Lymphoma

CNS§

Tumors

NeuroblastomaRetinoblastomaRenal 

Tumors

Hepatic 

Tumors

Bone 

Tumors

Soft Tissue 

Sarcomas

Germ Cell 

Tumors

Europe 130.9 42.4 14.3 28.1 9.8 3.8 8.6 1.4 5.4 8.3 4.0

France 135.6 41.3 15.7 28.2 13.5 4.2 9.3 1.3 6.6 7.4 4.0

Italy 158.0 53.9 18.6 32.7 13.4 3.9 8.6 1.8 7.5 9.2 3.8

United Kingdom 121.0 41.0 11.1 27.6 8.6 4.0 7.7 1.1 4.9 8.0 3.7

Sweden 154.3 41.7 13.8 42.8 4.9 4.8 10.2 2.2 5.6 10.5 3.5

Turkey 115.6 41.4 19.6 16.8 7.6 3.3 6.7 1.1 3.9 7.6 4.1

Cyprus 170.0 53.0 15.7 40.1 22.3 0.0 11.3 - 7.9 9.8 -

Israel (Jews) 133.3 31.8 20.0 24.2 15.8 2.8 6.9 1.3 8.1 11.0 3.1

Israel (Arabs) 119.9 29.4 24,2 16.5 12.0 2.1 5.7 2.5 3.3 13.6 3.6

Egypt 130.9 31.9 37.7 16.9 9.5 2.4 5.4 1.9 8.6 7.9 2.2

Jordan 114.8 39.2 19.0 18.9 6.1 4.6 5.1 1.1 6.0 6.3 3.4

Germany 128.7 44.8 14.5 24.3 11.6 3.4 8.9 1.3 5.6 8.5 4.5

Spain 137.9 41.1 19.3 27.6 12.6 3.6 7.6 1.8 7.6 9.0 3.8

US SEER 153.3 50.4 13.5 32.5 11.2 5.6 9.2 2.9 5.2 10.8 5.3

*Rates are per 1,000,000 and are age-standardized to the World Standard Million.

†The symbols “-” = 1-2 cases; and “[numeral]” (italic) = 0 or 3-15 cases.

‡The period covered is different for each population and ranges from 1968-99. See http://www-dep.iarc.fr/accis.htm for details.

Sources: Data on Cyprus, Egypt, Israel, and Jordan are from the MECC data set, and US SEER data are from the SEER Program, National Cancer Institute. Data from other countries are from the Automated Childhood Cancer 

Information System (ACCIS), http://www-dep.iarc.fr/accis.htm.

§CNS refers to central nervous system.
 MECC Monograph 149

Childhood Cancer Chapter 15

4. CNS tumors were the second most common neoplasms after 

leukemia in Cyprus, particularly in females (55.6), with a total 

ASR of 40.1. 

Within the MECC registries, the pattern of rates in Cyprus 

showed a similarity to the Western world and somewhat differed 

from other MECC countries. This may be due to genetic 

differences between the Cypriots and Arabs and Jews, or to 

differences in environmental factors in these populations, and 

needs further investigation. The situation is similar to that in 

Uruguay, where the incidence and types of childhood tumors were 

found to be closer to those in North America and Western Europe 

than in Latin America [20].

5. The rates of other types of childhood tumors in MECC 

countries were not substantially different from those in the 

Western world. It is interesting to note the similar ASRs of total 

childhood tumors in Turkey (115.6) and Jordan (114.8). 

The MECC registration system has provided useful information 

about the incidence of childhood cancers in Middle Eastern 

countries and should be continued. The higher incidence rate of 

lymphoma in Egyptians and Israeli Arabs requires further studies 

from the environmental point of view, including viral (EBV) and 

nutritional factors. EBV infection has been found to be strongly 

associated with malignant lymphomas (Hodgkin and Burkitt’s 

lymphoma) serologically and at molecular levels in Turkish 

children [14,15], so should be investigated further. An important 

future addition to the registration program would be the collection 

of survival data for children with malignant disease. 

REFERENCES

[1] Stiller CA. Epidemiology and genetics of childhood cancer. Oncogene 

2004;23:6429-44.

[2] Steliarova-Foucher E, Stiller C, Kaatsch P, Berrino F, Coebergh JW, 

Lacour B, et al. Geographical patterns and time trends of cancer 

incidence and survival among children and adolescents in Europe 

since the 1970s (the ACCIS project): an epidemiological study. Lancet 

2004;364:2097-105.

[3] International Agency for Research on Cancer. ACCIS: automated childhood cancer information system. 2006. Available at: http://www-dep.

iarc.fr/accis.htm. [Last Accessed: 1/06].

[4] Gatta G, Corazziari I, Magnani C, Peris-Bonet R, Roazzi P, Stiller C. 

Childhood cancer survival in Europe. Ann Oncol 2003;14:v119-v127.

[5] Gurney JG, Bondy ML. Epidemiologic research methods and childhood 

cancer. In: Pizzo P, Poplack DG, editors. Principles and practice of pediatric oncology, fourth edition. Philadelphia (PA): Williams & Wilkins; 

2001. p. 13-20.

[6] Pinkerton CR, Cushing P, Sepion B. Epidemiology and aetiology of 

childhood cancer. In: Childhood cancer management: a practical handbook. London (UK): Arnold; 1994. p. 28-41.

[7] Parkin DM, Kramarova E, Draper GJ, Masuyer E, Michaelis J, Neglia J, 

et al. International incidence of childhood cancer. IARC publication no. 

144. Lyon (France): International Agency for Research on Cancer; 1998.

[8] Kramarova E, Stiller CA, Ferlay J, Parkin DM, Draper GJ, Michaelis J, 

et al. The international classification of childhood cancer. IARC technical report no. 29. Lyon (France): International Agency for Research on 

Cancer; 1997.

[9] Parkin DM, Stiller CA, Draper GJ, Bieber CA, Terracini B, Young JL, et 

al. International incidence of childhood cancer. IARC scientific publications no. 87. Lyon (France): International Agency for Research on 

Cancer; 1988.

[10] Parkin DM, Stiller CA, Draper GJ, Bieber CA. The international incidence of childhood cancer. Int J Cancer 1988;42:511-20.

[11] Pratt CB. Some aspects of childhood cancer epidemiology. Pediatr Clin 

North Am 1985;32:541-56.

[12] Stiller CA, Bunch KJ, Lewis IJ. Ethnic group and survival from childhood cancer: report from the UK Children’s Cancer Study Group. Br J 

Cancer 2000;82:1339-43.

[13] Parkin DM, Stiller CA. Childhood cancer in developing countries: environmental factors. Int J Ped Hemat Oncol 1995;2:411-7.
150 MECC Monograph 

Childhood Cancer Chapter 15

[14] Çavdar AO, Pamir A, Gozdasoglu S. Hodgkin’s disease in children: 

clinico-epidemiologic and viral (Epstein-Barr virus) analyses. Med 

Pediatr Oncol 1999;32:18-23.

[15] Çavdar AO, Yavuz G, Babacan E, Gozdasoglu S, Unal E, Ertem U, et 

al. Burkitt’s lymphoma in Turkish children: clinical, viral [EBV] and 

molecular studies. Leuk Lymphoma 1994;14:323-30.

[16] Kamel AM, Ghaleb FM, Assem MM, Hindawy DS, Jaffe ES, Magrath 

IT. Phenotypic analysis of T-cell acute lymphoblastic leukemia in 

Egypt. Leuk Res 1990;14:601-9.

[17] Freedman LS, Barchana M, Al Kayed S, Qasem MB, Young JL, Edwards BK, et al. A comparison of population-based cancer incidence 

rates in Israel and Jordan. Eur J Cancer Prev 2003;12:359-65.

[18] Kutluk T. First national pediatric cancer registry in Turkey: a Turkish pediatric oncology group study (abstract). Ped Blood & Cancer 

2004;43:452.

[19] Fidaner C, Eser SY, Parkin DM. Incidence in Izmir in 1993-1994: first 

results from Izmir Cancer Registry. Eur J Cancer 2001;37:83-92.

[20] Castillo L, Fluchel M, Dabezies A, Pieri D, Brockhorst N, Barr R. 

Childhood cancer in Uruguay: 1992-1994. Incidence and mortality. Med 

Pediatr Oncol 2001;37:400-4.