Linkage

National Cancer Institute

Division of Can c er E p i d emiology an d G eneti c s

U.S. Department 

of Health and

Human Services

National Institutes

of Health

At the December meeting of NCI’s National Cancer Advisory Board (NCAB), 

three DCEG investigators presented recent findings demonstrating the impact 

that occupational and environmental epidemiology has on public policy. Joseph F. 

Fraumeni, Jr., M.D., Division Director, began the report with an overview of the 

Division’s occupational and environmental research portfolio. He explained that 

epidemiology allows researchers to discover carcinogens that are difficult to find 

using experimental approaches. Of particular importance are studies of workplace 

exposures, which are usually greater, more frequent, and longer in duration than 

exposures in the general population. Occupational studies allow researchers to discover mechanisms of carcinogenicity by integrating epidemiology, toxicology, and 

genetics. Noting that such studies have uncovered many established or probable 

human carcinogens, Dr. Fraumeni described some of the benefits of the studies: 

occupational groups can act as sentinels for risks from lower-level exposures in 

the general population, and the occupational setting affords special opportunities 

for primary prevention. Some of the DCEG studies have been conducted in highincidence areas detected by the U.S. cancer mortality atlases published by DCEG 

scientists. These and other studies have informed public policy measures, including the setting of environmental regulations.

To illustrate the 

role of epidemiology in public 

policy, Nathaniel 

Rothman, M.D., 

M.P.H., M.H.S., 

Occupational and 

Environmental 

Epidemiology 

Branch (OEEB), 

spoke on “Benzene 

exposure and risk 

of leukemia and 

lymphoma.” For 

more than 20 years, 

DCEG investigators 

have collaborated 

with the Chinese 

Public Policy Impact of Occupational and 

Environmental Epidemiology

March 2010 • Number 38

In This Issue:

D-FARE Winners, 4

Joseph Gastwirth 

Honored, 5

Margaret Spitz Joins 

DCEG, 5

Visiting Scholars 

Laurence Kolonel and 

Elizabeth Fontham, 6

DCEG Annual Town 

Meeting, 8

Profile of Rachael 

StolzenbergSolomon, 10

Profile of Rose Yang, 12

HREB Distinguished 

Lecturer Jack Cuzick, 14

Consortium Studies 

Lung Cancer in Asia, 15

Sallie Rosen Kaplan 

Fellow, 15 

Update on InterLymph 

Consortium, 16

Cohort Consortium 

Annual Meeting, 17

Scientific Highlights, 18

Major Editorials, 

Commentaries, and 

Reviews, 24

DCEG People in the 

News, 26

Comings...Goings, 29

30 Years of U.S.–China 

Cancer Research, 32

NCAB Presenters: Joseph Fraumeni, Qing Lan, Laura Beane Freeman, and 

Nathaniel Rothman with OEEB Chief Debra Silverman (center).
DCEG Linkage 2

DCEGLinkage

DCEG Linkage is a publication of the Division 

of Cancer Epidemiology and Genetics, National 

Cancer Institute. The newsletter is available 

online at http://www.dceg.cancer.gov.

Joseph F. Fraumeni, Jr., Director

Shelia Hoar Zahm, Deputy Director

Co-managing Editors

Samantha Nhan (nhans@mail.nih.gov)

Cherie M. Vitartas (vitartascm@mail.nih.gov)

Scientific Highlights Editor

Patricia Madigan (madiganp@mail.nih.gov)

DCEG Linkage Reporters

Epidemiology and Biostatistics Program

Sarah Del Castillo (delcastillos@mail.nih.gov)

Biostatistics Branch

Prisca Fall-Keita (fallpn@mail.nih.gov)

Clinical Genetics Branch

June A. Peters (petersju@mail.nih.gov)

Genetic Epidemiology Branch

Barbara Rogers (rogersb2@mail.nih.gov)

Hormonal and Reproductive Epidemiology Branch

Patricia Madigan (madiganp@mail.nih.gov)

Infections and Immunoepidemiology Branch

Cindy Chang (changcm@mail.nih.gov)

Laboratory of Translational Genomics

Tammy Yeager (yeagerta@mail.nih.gov)

Nutritional Epidemiology Branch

Alison Mondul (mondulam@mail.nih.gov)

Occupational and Environmental Epidemiology Branch

Gabriela Cadena (cadenag@mail.nih.gov)

Radiation Epidemiology Branch

Jenna Nober (noberj@mail.nih.gov)

DCEG Committee of Scientists

Katherine A. McGlynn (mcglynnk@mail.nih.gov)

DCEG Representatives to the NIH Women Scientists 

Advisory Group

Patricia Hartge (hartgep@mail.nih.gov)

Mary Ward (wardm@mail.nih.gov)

DCEG Representative to the NIH Tenure-track 

Investigators Committee

Sam Mbulaiteye (mbulaits@mail.nih.gov)

DCEG Representatives to the NIH Staff Scientists/Staff 

Clinicians Organization

Dalsu A.N. Baris (barisd@mail.nih.gov)

Mark J. Roth (rothm@mail.nih.gov)

DCEG Representatives to the NIH Fellows Committee

Mercy Guech-Ongey (guechome@mail.nih.gov)

Gila Neta (netagil@mail.nih.gov)

Palladian Partners, Inc. 

Elaine Garber (egarber@palladianpartners.com)

Center for Disease Control and Prevention on studies of occupational exposure 

to benzene that have greatly increased 

our understanding of the carcinogenic 

risks of benzene and helped set standards for benzene exposure in the United 

States and abroad. In the largest cohort 

study to establish a link between benzene 

exposure and acute non-lymphocytic 

leukemia (ANLL) and myelodysplastic 

syndrome, the group reported in 1997 

that increased risk of ANLL and 

myelodysplastic syndrome was present 

at exposures lower than 10 parts per 

million. Benzene was also linked to 

other forms of leukemia and to suggestive excesses of non-Hodgkin lymphoma 

(NHL) and lung cancer. Researchers 

followed up on these findings by conducting molecular epidemiology studies that used a panel of biomarkers to 

identify the underlying mechanisms of 

benzene-related leukemia, including 

precursor conditions and susceptibility 

states. Hematologic toxicity was found to 

occur at lower levels of benzene exposure 

than generally appreciated, inspiring a 

larger study that uncovered hematotoxicity among workers exposed to less than 

1 part per million in the air, the current 

U.S. occupational standard. Further analyses identified several genetic variants 

associated with a decrease in white blood 

cell counts among exposed workers.

The findings from these studies led to a 

lower occupational standard in China 

and greatly informed the risk assessment 

process for environmental exposures 

in the United States. In addition, they 

helped prompt the U.S. Environmental 

Protection Agency (EPA) to establish a 

rule limiting the benzene content in gasoline and to adopt controls on passenger 

vehicles and portable fuel containers to 

reduce the emission of hazardous air 

pollutants. In October 2009, the International Agency for Research on Cancer 

(IARC) used the NCI and other data 

to conclude that, in addition to ANLL, 

there is limited evidence that benzene 

causes acute and chronic lymphocytic 

leukemia, NHL, and multiple myeloma. 

“The decision by the IARC working 

group provides support for the hypothesis that benzene may be associated with 

one or more subtypes of lymphoma, a 

finding that is currently being followed 

up by DCEG investigators and other 

research groups,” Dr. Rothman noted. 

Investigators in OEEB and the Radiation 

Epidemiology Branch (REB), along with 

Martha S. Linet, M.D., M.P.H., Chief 

of REB, are pursuing the cancer risks of 

different levels of benzene exposure and 

searching for carcinogenic mechanisms, 

including markers of genetic susceptibility. DCEG investigators also are collaborating with Stephen J. Chanock, M.D.,

Director of the Core Genotyping Facility 

and Chief of the Laboratory of Translational Genomics, on a genome-wide 

scan of benzene-induced hematotoxicity.

In the next presentation, Laura Beane 

Freeman, Ph.D. (OEEB), spoke on 

“Formaldehyde exposure and the risk of 

nasopharyngeal cancer and leukemia.” 

In 1995, the Occupational Safety and 

Health Administration estimated that 

2.1 million U.S. workers were exposed 

to formaldehyde. A substantially larger 

number in the general population are 

exposed to lower levels of formaldehyde 

through pressed-wood products, glues 

and adhesives, paper product coatings, 

insulation materials, cigarette smoke, 

automobile emissions, and unvented 

fuel-burning appliances. In the early 

1980s, Aaron E. Blair, Ph.D., M.P.H., 

scientist emeritus of OEEB, established 

a cohort of workers in formaldehydeproducing and formaldehyde-using 

plants. Investigators found an increased 

risk of nasopharyngeal cancer and a 

possible excess of lymphohematopoietic 

malignancies. In the most recent analysis 

of lymphohematopoietic malignancies, 

which included follow-up through 2004, 

Dr. Beane Freeman found that the excess 
March 2010 3

risk was most pronounced for myeloid 

leukemia. In addition, DCEG studies 

of professional groups exposed to formaldehyde, such as pathologists, anatomists, and embalmers, showed excess 

mortality from lymphohematopoietic 

malignancies, particularly leukemia. 

To follow up on these findings, DCEG 

scientists updated a study of funeral 

industry workers that revealed a threefold increased risk of myeloid leukemia associated with longest duration 

of embalming, greatest number of 

embalmings performed, and highest 

cumulative exposure to formaldehyde.

To investigate the biological plausibility 

of leukemia-associated risks from formaldehyde exposure, NCI investigators 

turned to the multidisciplinary research 

approach used in the benzene studies. 

They teamed with colleagues at the 

Guangdong Poison Control Center and 

the University of California, Berkeley, 

to conduct a cross-sectional molecular 

epidemiology study of Chinese workers 

exposed to formaldehyde. The results 

showed significantly lowered peripheral 

blood cell counts among formaldehydeexposed workers and leukemia-specific 

chromosome changes in myeloid progenitor cells.

Dr. Beane Freeman emphasized that 

“epidemiologic studies combined with 

emerging molecular technologies are 

essential in addressing important scientific questions, the answers to which 

have implications for protecting the 

public’s health” and described the risk 

assessment process that has taken place 

in the evaluation of formaldehyde. In 

2004, IARC classified formaldehyde 

as a human carcinogen because of its 

association with nasopharyngeal cancer 

in humans and nasal cancer in rodents 

and found strong but not sufficient 

evidence for leukemia. In 2009, using 

additional epidemiological and mechanistic evidence provided by NCI and 

other groups, an IARC working group 

determined that sufficient evidence was 

found to link formaldehyde to leukemia, 

particularly myeloid leukemia. Also in 

2009, the National Toxicology Program 

convened an outside expert panel for its 

Report on Carcinogens that cited sufficient evidence for leukemia as well as 

nasopharyngeal and sinonasal cancers. 

The EPA is updating its risk assessment 

of formaldehyde, which will be used to 

determine regulatory standards.

Qing Lan, M.D., Ph.D., M.P.H. (OEEB), 

concluded the NCAB session with a 

talk on “Indoor air pollution from coal 

combustion and risk of lung cancer.” For 

more than a decade, DCEG researchers 

have collaborated with Chinese scientists 

on studies of indoor air pollution from 

solid fuel use in Xuanwei County, China. 

This type of pollution is the eighth largest risk factor for global disease. Half 

of the world’s population is exposed to 

smoke from cooking or heating with 

solid fuels, and the greatest exposures 

occur in developing countries. 

“The Xuanwei region provides a unique 

opportunity to study lung cancer associated with environmental pollution,” 

Dr. Lan said. “It has the highest prevalence of lung cancer in China, and the 

attributable risk of lung cancer from 

unvented smoky coal burning is greater 

than 90 percent. Also, the lung cancer 

mortality rates for men and women are 

similar, yet nearly all women and few 

men cook, whereas most men and nearly 

no women smoke tobacco.”

In addition to linking indoor air pollutants to lung cancer, two studies have 

demonstrated a reduction in lung cancer 

risk associated with stove improvements. 

The first study, published in 2002 by 

Dr. Lan and colleagues at the EPA and 

the Chinese Academy of Preventive 

Medicine, showed that use of vented 

stoves lowered lung cancer risk by 41 

percent in men and 46 percent in women 

and that installing a vented stove could 

cut indoor levels of air pollution by 

more than 65 percent. The second study, 

published in 2008, found that replacing 

The International Agency for Research on Cancer (IARC) monographs—a series of scientific 

reviews that evaluates chemical, physical, and micro-agents for their potential carcinogenic 

risks to humans—have been published annually since 1971 and have involved more than 1,000 

scientists from more than 50 countries. This year, IARC takes pride in releasing its 100th volume, 

which reviews and updates evidence on the human carcinogens identified to date. For each agent, 

the volume provides a general description of exposure data; a summary of epidemiologic studies 

on cancer risk among humans; a summary of the experimental data, including animal bioassays; 

mechanistic and other relevant data; and an overall evaluation and rationale used to classify 

each agent for its carcinogenic potential.

To produce Volume 100, IARC convened a series of interdisciplinary working group meetings 

to evaluate the evidence of carcinogenicity for each agent. Several DCEG investigators participated 

in the reviews. Mark Schiffman, M.D., M.P.H., Clinical Genetics Branch, served on the expert 

panel evaluating biological agents; Dr. Kenneth P. Cantor, formerly of the Occupational and 

Environmental Epidemiology Branch (OEEB), participated in the review of evidence for metals, 

arsenic, dust, and fibers; Michael C.R. Alavanja, Dr.P.H., and Qing Lan, M.D., Ph.D., M.P.H., 

both of OEEB, were members of the working group on lifestyle risk factors; and Laura Beane 

Freeman, Ph.D., and Nathanial Rothman, M.D., M.P.H., M.H.S., both of OEEB, evaluated 

chemical agents and related occupations. 

—Alexandra Ekblom, M.P.H.

IARC Produces Its 100th Monograph 
DCEG Linkage 4

indoor stoves with portable stoves, 

which are filled with coal, lighted once 

daily outdoors, and brought indoors 

after visible smoke has diminished 

substantially, was associated with a 

reduction in lung cancer mortality risk 

of 38 percent in men and 59 percent in 

women. Replacing indoor stoves with 

portable stoves is a cost-effective intervention that could substantially improve 

health in developing countries.

In studies analyzing risks according 

to the type of coal used, Dr. Lan and 

colleagues showed that coal emissions that contained the highest levels 

of polycyclic aromatic hydrocarbons 

(PAHs) were associated with the highest 

lung cancer risk. In studies of geneenvironment interactions, Dr. Lan 

reported a twofold increase in the risk 

of developing lung cancer among people 

who carried a homozygous deletion in 

the GSTM1 gene, which codes for an 

enzyme that detoxifies PAHs. Based 

largely on DCEG’s research on indoor 

air pollution, IARC classified indoor 

emissions from household combustion of coal as carcinogenic to humans. 

DCEG’s findings are also being used to 

develop the World Health Organization Guidelines for Indoor Air Quality 

and to encourage improved home 

ventilation and replacement of coal 

with cleaner sources of energy for heating and cooking.

Dr. Lan discussed plans to evaluate the 

environmental and genetic determinants 

of lung cancer among women in Asia. 

An international consortium involving 

several Asian countries has been developed and will include a genome-wide 

association study (GWAS) of lung cancer 

with a special emphasis on reasons for 

the excess incidence of lung adenocarcinoma among females who have never 

smoked.

Dr. Lan concluded, “These collaborative 

efforts will help to better estimate doseresponse relationships between lung 

cancer and coal-combustion products; 

the effects of other indoor pollutants, 

such as cooking oil volatiles from hightemperature wok cooking; and the interactions with inherited genetic variants.” 

Dr. Lan hopes that these studies will lead 

to a more comprehensive understanding of the causal factors in lung cancer 

and ultimately help shape public health 

measures to reduce the incidence of this 

lethal cancer around the world. n

—Cherie M. Vitartas, M.P.H.

DCEG Fellows Award for Research Excellence 

The DCEG Fellows Award 

for Research Excellence 

(D-FARE) recognizes fellows 

who have made exceptional 

contributions to scientific 

research projects. Their 

contributions may include 

formulating the research idea, 

developing the study design, 

conducting fieldwork analysis, 

or interpreting the results, and 

the fellow must have had a 

major role in drafting a manuscript. Special consideration is 

given to projects in which fellows demonstrate growth beyond the discipline of their previous training. Awardees receive funding 

to present their research at a scientific meeting.

The D-FARE program was established because attendance at scientific meetings is integral to 

the fellowship experience. The awards enable a greater number of fellows to participate in 

scientific meetings, where they are exposed to new scientific developments and can establish 

vital connections with other scientists. 

Recipients were announced at the DCEG Town Meeting in October, and funds must be used by 

the end of the 2010 fiscal year. 

The 2009 D-FARE recipients are: 

H. Dean Hosgood, III, Ph.D., Occupational and Environmental Epidemiology Branch (OEEB): 

Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study.

Stella Koutros, Ph.D. (OEEB): Pesticide exposure modifies the association between variants 

on chromosome 8q24 and prostate cancer.

Huilin Li, Ph.D., Biostatistics Branch: Using cases to strengthen inference on the association between 

single nucleotide polymorphisms and a secondary phenotype in genome-wide association studies.

Alison Mondul, Ph.D., Nutritional Epidemiology Branch: Serum retinol and risk of prostate cancer 

in the ATBC.

Meredith Shiels, Ph.D., Infections and Immunoepidemiology Branch: Age at cancer diagnosis 

among those with AIDS compared to the general population.

Hannah P. Yang, Ph.D., Sc.M., Hormonal and Reproductive Epidemiology Branch: Common 

genetic variation in the sex hormone metabolic pathway and endometrial cancer risk: Pathwaybased evaluation of candidate genes.

D-FARE Winners: (front) Meredith Shiels, Hannah Yang, and Huilin Li; 

(back) Alison Mondul, Dean Hosgood, and Stella Koutros.
March 2010 5

to increase efficiency. Dr. Pfeiffer led 

the resulting work that described how 

to estimate joint allele frequencies at two 

loci, as well as a linkage disequilibrium 

parameter, in the presence of pooled 

assay misclassification. 

While at BB, Dr. Gastwirth became 

interested in the measurement of health 

disparities and proposed the PetersBelson method of regression adjustment. 

In this method, a large population, such 

as white males, is used to fit a regression model for a health-related event, 

such as colorectal cancer screening. 

This model is then used to estimate the 

expected values for a small subgroup, 

such as black males. A comparison is 

then made between the regression predictions and the observed health events 

in the subgroup. Barry I. Graubard, 

Ph.D. (BB), and former BB fellow Dr. R. 

Sowmya Rao led work that showed how 

the Peters-Belson method could be used 

to interpret disparities in cancer screening rates and how the method could be 

adapted for data from complex surveys. 

Dr. Gastwirth’s other collaborative 

projects include power calculations for 

genotype- and allele-based score tests in 

association studies centered on families, 

trend tests for association with good 

power regardless of the mode of genetic 

inheritance, and modeling risk with 

percentiles of exposure. n

—Mitchell H. Gail, M.D., Ph.D.

Joseph Gastwirth Honored

J

oseph L. Gastwirth, Ph.D., an 

adjunct investigator in the Biostatistics 

Branch (BB), was honored at a symposium sponsored by George Washington 

University in August. The symposium 

highlighted Dr. Gastwirth’s contributions to statistical theory, statistics for 

economics and law, and biostatistics. 

Two Festschrifts were published from 

the symposium as special issues of the 

journals Statistics and Its Interface and

Law, Probability and Risk. 

Dr. Gastwirth was a visiting scientist in 

BB from 1999 to 2000 and has continued 

to collaborate with several Branch members. In a project with Ruth M. Pfeiffer, 

Ph.D. (BB), he proposed pooling DNA 

samples as a means to protect confidentiality in dealing with genetic data and 

Margaret R. Spitz, M.D., M.P.H., 

professor and former chair of the 

Department of Epidemiology at The University of 

Texas M.D. Anderson Cancer Center, joined DCEG 

as a visiting advisor in September. Dr. Spitz is a 

luminary in molecular epidemiology and is internationally noted for her work on tobacco-related 

cancers. Her research focuses on interindividual 

variation in susceptibility to the development of 

lung and other tobacco-related cancers in addition 

to the construction of predictive risk models for 

determining high-risk subgroups of smokers. She 

co-led one of the first genome-wide association 

studies (GWAS) of lung cancer, identifying 

a region of the long arm of chromosome 15 as 

the “top hit.” She has led and participated in 

Specialized Programs of Research Excellence 

(SPOREs) for lung, prostate, and head and neck 

cancers as well as international consortia to 

advance epidemiologic research on lung cancer. 

Dr. Spitz has developed risk prediction models 

for lung cancer using epidemiologic- , clinical- , 

Margaret Spitz addresses DCEG staff at the Division’s 

Annual Town Meeting.

Margaret Spitz Joins DCEG as a Visiting Advisor

and molecular-based biomarkers. She also published a seminal article advancing “integrative epidemiology,” a concept that links genetic and other 

biomarkers to the study of high-risk behaviors and 

disease risk as well as disease progression, prognosis, and response to treatment. 

Dr. Spitz, using her extensive experience and 

breadth of knowledge, will advise on strategies 

for DCEG research programs on genetic and 

environmental factors related to cancer etiology, 

including the genetics of lung cancer and nicotine 

dependence. She also will advise on the development and expansion of research platforms for 

future initiatives, including plans for an integrative epidemiology program that incorporates new 

initiatives in the area of pharmacogenomics. In 

addition, Dr. Spitz will help foster intramural and 

extramural collaborations, including large-scale 

consortial activities, and will also be available 

for mentoring junior investigators and providing 

guidance on existing fellowship programs.

“We are honored that Dr. Spitz has agreed to 

work part-time in DCEG, where her wisdom and 

strategic advice will be invaluable in helping us to 

develop research directions for the future,” stated 

Joseph F. Fraumeni, Jr., M.D., Division Director. 
DCEG Linkage 6

DCEG Welcomes Visiting Scholars Drs. Kolonel and Fontham

DCEG welcomed two leading epidemiologists in the fall of 2009 as 

part of its Visiting Scholars Program. 

In September, Dr. Laurence N. Kolonel, 

Deputy Director of the Cancer Research 

Center of Hawaii, was recognized for his 

leadership and vision in epidemiology, 

particularly in the areas of racial and 

ethnic health disparities. In December, 

Dr. Elizabeth Fontham, a professor of 

epidemiology and Dean of the Louisiana 

State University (LSU) School of Public 

Health, was honored for her contributions to cancer epidemiology and public 

health. Initiated in 2004, the Visiting 

Scholars Program promotes intramuralextramural scientific collaboration and 

idea-sharing through intensive two-day 

visits that include a keynote seminar, 

scientific roundtables and discussions, 

one-on-one meetings, and sessions with 

DCEG fellows and women scientists.

Dr. Kolonel received an M.D. from 

Harvard Medical School and, following 

an internship at the University of California, San Francisco Medical Center 

at Mt. Zion Hospital, he obtained an 

M.P.H. and Ph.D. in epidemiology at 

the University of California, Berkeley. 

After serving as an epidemiologist in 

the United States Air Force, Dr. Kolonel 

joined the Cancer Research Center 

of Hawaii in 1974 and developed a 

comprehensive research program 

on the role of diet and nutrition in 

cancer etiology. Many of his studies 

were designed to clarify reasons for 

the disparities in cancer incidence 

among the ethnic and racial groups in 

Hawaii as well as explain the changing patterns of cancer among migrant 

populations from Asia. 

For the past 16 years, Dr. Kolonel has 

been a principal investigator of the NCIsupported Multiethnic Cohort Study. 

This landmark study, established in 

Hawaii and Los Angeles, California 

during 1993 to 1996, is composed of 

more than 215,000 men and women, 

including those of African, Asian, 

Latino, Native Hawaiian, and Caucasian ancestry. It is unique among existing population cohort studies in its 

ethnic diversity and representation 

of minorities. 

In his Visiting Scholar seminar titled 

“Prostate cancer etiology: What do we 

really know?” Dr. Kolonel outlined the 

epidemiologic characteristics of prostate 

cancer, including the rising incidence 

with advancing age; the tendency to 

familial occurrence; the extraordinarily 

high incidence of latent tumors; and the 

striking racial variation, with relatively 

high rates in African Americans and 

low rates in Asian Americans. The available evidence for dietary risk factors 

was a particular focus of his lecture, but 

attention was also given to recent results 

from genome-wide association studies 

(GWAS) and the role of inflammation and metabolic changes as etiologic 

mechanisms. He concluded his talk by 

stressing the importance of looking at 

gene-environment interactions through 

molecular epidemiology. 

During the remainder of his visit, which 

was hosted by Rashmi Sinha, Ph.D., 

Nutritional Epidemiology Branch 

(NEB), Dr. Kolonel attended a series of 

discussions focusing on the nutritional 

epidemiology of cancer, epigenetic 

variation in mediating cancer risk, risk 

factors for prostate cancer, the association between meat consumption and 

the risks for certain cancers, and the 

future of multiethnic and minoritybased cohort studies. These sessions 

were moderated, respectively, by DCEG 

scientists Arthur Schatzkin, M.D., 

Dr.P.H. (NEB), Mitchell H. Gail, M.D., 

Ph.D., Biostatistics Branch (BB), 

Christian C. Abnet, Ph.D., M.P.H.

(NEB), Lee E. Moore, Ph.D., Occupational and Environmental Epidemiology 

Branch (OEEB), Demetrius Albanes, 

M.D. (NEB), Ann W. Hsing, Ph.D., 

Hormonal and Reproductive Epidemiology Branch, Amanda J. Cross, Ph.D. 

(NEB), Rachael Stolzenberg-Solomon, 

Ph.D., M.P.H., R.D. (NEB), and Robert 

N. Hoover, M.D., Sc.D., Director of the 

Epidemiology and Biostatistics Program. Dr. Kolonel also participated in 

a meeting of DCEG Women Scientists, 

where principal investigators, staff scientists/clinicians, and fellows discussed 

topics related to mentoring and career 

advancement. 

Joseph F. Fraumeni, Jr., M.D., DCEG 

Director, applauded Dr. Kolonel’s contributions to cancer research and for 

his service on important national and 

international committees, including 

the NCI Board of Scientific Counselors. 

About his visit, Dr. Kolonel commented, 

“It was a great pleasure to meet with 

NCI colleagues to discuss the common 

issues we face and the priorities for 

future research in cancer epidemiology 

and prevention.”

Laurence Kolonel discusses the epidemiology of 

prostate cancer.
March 2010 7

Elizabeth Fontham with Michael Alavanja and Joseph Fraumeni.

DCEG Visiting Scholar Dr. Fontham 

received a doctorate in epidemiology 

at Tulane University’s School of Public 

Health and later joined the Department of Pathology at the LSU School 

of Medicine, where she rose to the 

rank of professor. Since 2004, she has 

been dean of the LSU School of Public 

Health. She has led research on a broad 

range of cancer risk factors, making 

major contributions to genetic and environmental epidemiology. Her current 

work focuses on etiologic studies of gastric cancer, a multicenter study of prognostic indicators of prostate cancer in 

African American and Caucasian men, 

and genetic and environment interactions influencing pancreatic cancer. She 

serves as the Immediate Past President 

of the American Cancer Society, is on 

the board of the Louisiana Cancer and 

Health Foundation, and has had many 

leadership positions in professional 

organizations. “The combination of 

research, education, and service that 

Dr. Fontham has provided has been 

extremely important to this country 

and the world,” Dr. Fraumeni stated. 

The topic of her Visiting Scholar Seminar was “Association of Helicobacter 

pylori infection and the cancers of 

specific organs.” 

Dr. Fontham began the lecture with 

a history of H. pylori research and its 

relationship to gastric cancer as a 

“co-carcinogenic” factor. H. pylori infection is prevalent among 50 percent of 

the world’s population and is linked to 

socioeconomic status. It is characterized 

by person-to-person transmission, especially among young children in crowded 

living situations. She pointed out the 

many questions about the risks associated with non-cardia gastric cancers and 

MALT lymphoma as well as possible 

relationships to esophageal, hepatocellular, pancreatic, and colorectal cancers. 

She stressed that bacterial virulence, 

genetic susceptibility, and inflammatory 

responses play major roles in cancer 

risk. Dr. Fontham indicated areas for 

further research, including epidemiologic and mechanistic questions about 

the potential association with nongastric cancers. 

During the remainder of her visit, 

which was hosted by Michael C.R. 

Alavanja, Dr.P.H. (OEEB), and Debra 

T. Silverman, Sc.D., Chief of OEEB, 

Dr. Fontham met with investigators 

from DCEG and participated in a series 

of roundtable discussions. H. Dean 

Hosgood, III, Ph.D. (OEEB), and Dr. 

Alavanja moderated a session on recent 

developments in lung cancer epidemiology. Catherine Schairer, Ph.D. (BB), 

led a roundtable discussion of data 

related to recommendations for breast 

mammography screening for women 

ages 40–49. This was followed by a 

discussion led by William F. Anderson, 

M.D., M.P.H. (BB), on cancer surveillance and Surveillance, Epidemiology, 

and End Results (SEER) registries. Dr. 

Fontham also met with the Upper G.I. 

Working Group in a discussion led 

by Neal D. Freedman, Ph.D., M.P.H. 

(NEB). Dr. Fontham spoke about the 

carcinogenicity of nitrates and other 

environmental pollutants in a meeting hosted by Mary H. Ward, Ph.D. 

(OEEB). Dr. Stolzenberg-Solomon 

hosted a discussion on pancreatic cancer, including its relation to ABO blood 

type, H. pylori, and environmental and 

nutritional risk factors. Dr. Fontham 

also met with DCEG fellows during a 

brown-bag lunch hosted by Jackie 

Lavigne, Ph.D., M.P.H., Chief of 

DCEG’s Office of Education, and participated in an OEEB fellows’ roundtable 

hosted by Gabriella Andreotti, Ph.D. 

(OEEB). In addition, the DCEG Women 

Scientists Advisors hosted a lunch with 

Dr. Fontham, where the discussion centered on the topic of leadership development of mid- and senior-level women 

scientists.

Dr. Fontham concluded her visit by 

thanking DCEG staff and scientists. 

“It’s been a pleasure to meet with the 

special mix of scientists gathered in 

DCEG. It has been nice to see old 

friends and familiar faces.”

Following each Visiting Scholar Seminar, Dr. Fraumeni presented Dr. Kolonel 

and Dr. Fontham with DCEG Visiting 

Scholar Awards in recognition of their 

major scientific accomplishments. n

—Alexandra Ekblom, M.P.H.
DCEG Linkage 8

DCEG Annual Town Meeting

Last October, DCEG held its Annual 

Town Meeting to celebrate the 

accomplishments of Division members during the past year. Joseph F. 

Fraumeni, Jr., M.D., Division Director, 

welcomed the staff and featured speaker 

Margaret R. Spitz, M.D., M.P.H., a 

special advisor to DCEG and professor 

of epidemiology at The University of 

Texas M.D. Anderson Cancer Center. 

Shelia Hoar Zahm, Sc.D., DCEG Deputy 

Director, opened the meeting with an 

overview of the Division’s breadth of 

research and a summary of significant 

DCEG scientific publications, including 

new findings generated from genomewide association studies (GWAS). She 

also summarized increased activity at 

the Core Genotyping Facility, the DNA 

Extraction and Staging Laboratory, the 

biorepositories, and other infrastructure 

operations. Dr. Zahm concluded with a 

review of the honors and awards received 

by DCEG investigators, staff additions 

and departures, training activities, 

and other special events of 2009. 

Dr. Fraumeni introduced Dr. Spitz to 

the Division, remarking, “Her exceptional scientific career and leadership 

in epidemiologic research place Dr. 

Spitz in a class by herself. She will be 

an asset to the Division and NCI as an 

advisor and mentor to junior and senior 

investigators and through her ability 

to promote intramural and extramural 

collaborations.” 

In her presentation “Evolution of molecular epidemiologic research: Where will 

epidemiology go in the 21st century?” 

Dr. Spitz outlined the progression of 

the field of epidemiology from classical approaches to integrative molecular 

epidemiology and hypothesized about 

the promise that GWAS may hold for 

epidemiologic research. Using lung 

cancer as an example, Dr. Spitz illustrated how integrating molecular and 

genetic information with environmental 

exposures and lifestyle risk factors has 

not only led to a more comprehensive 

understanding of disease causation 

and progression but has also provided 

a means for improved prevention and 

treatment. She also described the added 

value genetic analysis may have for 

improving predictors of outcome. Dr. 

Spitz concluded her talk by outlining 

future directions that could incorporate 

genomic and molecular technologies 

into epidemiologic study designs, stating, 

“This is an exciting time to be a molecular epidemiologist.” Following her presentation, Dr. Spitz answered questions 

from the audience. 

Dr. Zahm then led the annual awards 

ceremony recognizing scientific contributions and outstanding service during 

the past year. The ceremony began with 

the Fellowship Achievement Awards, 

which honor fellows who have excelled 

during their time at DCEG and provide 

stipend increases at the next appointment 

renewal. Awards were given to Porcia 

Bradford, M.D., Genetic Epidemiology 

Branch; H. Dean Hosgood, III, Ph.D., 

Occupational and Environmental 

Epidemiology Branch (OEEB); Stella 

Koutros, Ph.D. (OEEB); Idan Menashe, 

Ph.D., Biostatistics Branch (BB); and 

Lisa Mirabello, Ph.D., Clinical 

Genetics Branch.

DCEG Special Appreciation and Recognition Awards were given to Dr. 

Christine Berg, Division of Cancer 

Prevention, for her dedicated efforts on 

behalf of the Prostate, Lung, Colorectal 

and Ovarian (PLCO) Cancer Screening 

Trial; Dr. Kenneth P. Cantor, formerly of 

Award Recipients with Joseph Fraumeni 

(top to bottom): Outstanding Research Paper 

by a Staff Scientist/Clinician Award recipients Joanne 

Colt and Alice Sigurdson; Outstanding Mentor Award 

recipients Christian Abnet and Ruth Pfeiffer; and 

Exemplary Service Award recipient Mark Sherman. 

(Photograph credit: Bill Branson)
March 2010 9

OEEB, for his career-long contributions 

to the research and training programs 

in environmental epidemiology; Amy 

Hutchinson, M.S., Director of Operations of the Core Genotyping Facility, 

for her outstanding contributions; Dr. 

Timothy Sheehy, SAIC-Frederick, Inc., 

for his work to add sample handling and 

Identifiler assays to the services available 

through the DNA Extraction and Staging Laboratory; and Monique St. Louis, 

NIH Office of Human Resources, for 

her superb and speedy work on the 

Division’s personnel actions.

Christian C. Abnet, Ph.D., M.P.H., 

Nutritional Epidemiology Branch, and 

Ruth M. Pfeiffer, Ph.D. (BB), received 

DCEG Outstanding Mentor Awards in 

recognition of their exceptional commitment to the growth and productivity of junior scientists. Dr. Abnet was 

described as “an exceptional scientist 

with wide-ranging expertise, strong 

quantitative skills, and an infectious 

excitement for science.” Dr. Pfeiffer was 

commended for her mentorship, which 

“extends far beyond the invaluable statistical expertise for which she is known.”

The DCEG Exemplary Service Award 

was given to Mark E. Sherman, M.D., 

Hormonal and Reproductive Epidemiology Branch, for his sustained research 

accomplishments and integration of 

cutting-edge pathology components 

into epidemiologic studies. His work has 

included determining whether unique 

methods exist to subdivide tumors 

into etiologically distinct subgroups 

and finding ways to measure novel tissue markers. Recognizing that DCEG’s 

archive of fixed and frozen pathology 

specimens was growing and that appropriate support was needed to examine 

tumors by molecular subtype and build 

tissue microarrays, Dr. Sherman developed a proposal for a specialized laboratory to provide oversight and improve 

quality control. He then worked to make 

the NCI Applied Molecular Pathology 

Laboratory a reality. Tissue samples from 

the Polish breast, endometrial, and ovarian cancer study, on which he has served 

as a co-investigator, are being used as the 

initial test specimens for this laboratory. 

This new resource combines the expertise of scientists from DCEG and the 

Center for Cancer Research and will be 

a critical component of future research 

in molecular epidemiology.

The spring 2009 winners of DCEG 

Intramural Research Awards, which 

were announced earlier in the year, 

also received plaques at the Annual 

Town Meeting. The entire event was 

coordinated by Samantha Nhan,

Office of Communications and 

Special Initiatives. n

Awards for Outstanding 

Research Paper by a Fellow 

or a Staff Scientist/Clinician

Six papers published in 2008 were selected for the 

Outstanding Research Paper by a Fellow Award, 

and two papers were selected for the Outstanding 

Research Paper by a Staff Scientist/Clinician Award. 

The Division’s Senior Advisory Group judged the 

competition based on the papers’ impact, innovation, and clarity of thought and language. 

The 2008 winning papers by fellows are: 

Jiyoung Ahn, Ph.D., Nutritional Epidemiology 

Branch (NEB): “Variation in KLK genes, prostatespecific antigen and risk of prostate cancer,” 

Nature Genetics

Sonja I. Berndt, Pharm.D., Ph.D., Occupational 

and Environmental Epidemiology Branch (OEEB): 

“Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk,” Human 

Molecular Genetics

Anil K. Chaturvedi, Ph.D., Infections and 

Immunoepidemiology Branch: “Incidence trends 

for HPV-related and HPV-unrelated oral squamous 

cell carcinomas in the U.S.,” Journal of Clinical 

Oncology

Neal D. Freedman, Ph.D., M.P.H. (NEB): 

“Cigarette smoking and subsequent risk of 

lung cancer in men and women: Analysis of a 

prospective cohort study,” Lancet Oncology

H. Dean Hosgood, III, Ph.D. (OEEB): “Portable 

stove use is associated with lower lung cancer 

mortality risk in lifetime smoky coal users,” 

British Journal of Cancer

James Li, Ph.D., Biostatistics Branch: “Improved 

correction for population stratification in GWAS by 

identifying hidden population structures,” Genetic 

Epidemiolgy

Winning papers by staff scientists are: 

Joanne S. Colt, M.P.H., M.S. (OEEB): “Organochlorine exposure, immune gene variation, and risk 

of NHL,” Blood

Alice J. Sigurdson, Ph.D., Radiation Epidemiology Branch: “Routine diagnostic X-ray examinations and increased frequency of chromosome 

translocation among U.S. radiologic technologists,” Cancer Research

Recipients of the Outstanding Research Paper by a Fellow Award with Joseph Fraumeni: Neal Freedman, 

Anil Chaturvedi, Joseph Fraumeni, Sonja Berndt, and Dean Hosgood. (Not Shown: Jiyoung Ahn and James LI.) 

(Photograph credit: Bill Branson)
DCEG Linkage 10

Rachael Stolzenberg-Solomon Seeks Answers to Pancreatic Cancer

Rachael Stolzenberg-Solomon, 

Ph.D., M.P.H., R.D., of the 

Nutritional Epidemiology Branch 

(NEB), attributes her long-standing 

research interest in pancreatic cancer 

to both inspiration and serendipity. 

The inspiration to study nutrition and 

cancer came from her father, a reproductive physiologist who conducted 

toxicology research. “Through discussions with my father, I grew up aware 

of the concept that mutagens and other 

exposures in food could contribute 

to cancer,” Dr. Stolzenberg-Solomon 

recalled. The serendipity came in the 

1990s, when she was working as a 

registered dietitian at Johns Hopkins 

Hospital. Dr. Stolzenberg-Solomon 

provided nutritional counseling and 

support to pancreatic cancer patients 

undergoing surgical resection of their 

tumors. “Patients with pancreatic cancer came from all over the country to 

be treated at Hopkins, so we saw many 

patients with this type of cancer,” 

Dr. Stolzenberg-Solomon said. “I was 

intrigued, because pancreatic cancer 

is so devastating and, yet, we had 

little understanding about its causes, 

other than a link to smoking.” She 

began noticing that many of the newly 

diagnosed patients suffered from macrocytic anemia, which may be caused by 

folate deficiency—an observation she 

went on to study as part of her doctoral 

dissertation work at the Johns Hopkins 

Bloomberg School of Public Health. 

Ultimately, Dr. Stolzenberg-Solomon’s 

research interests led her to NCI—

first as a predoctoral fellow in the 

Cancer Prevention Studies Branch 

of the former Division of Cancer 

Prevention and Control, later the 

Center for Cancer Research, and then 

as a postdoctoral fellow in the Division 

of Cancer Prevention and DCEG. She 

became a tenure-track investigator in 

NEB in 2002. 

Dr. Stolzenberg-Solomon’s epidemiologic work has focused on examining 

genetic, infectious, dietary, lifestyle, 

and other risk factors, including the 

presence of biomarkers, that may help 

reveal underlying mechanisms of carcinogenesis, particularly as they relate to 

pancreatic cancer. A primary approach 

of her research is using prospective data 

from cohort studies. Since 2006, Dr. 

Stolzenberg-Solomon’s efforts, in collaboration with other investigators at 

DCEG and extramurally, have focused 

on conducting and completing the first 

genome-wide association study (GWAS) 

for pancreatic cancer in a large-scale 

consortial effort (known as PanScan). 

The results of this GWAS, published 

in the September 2009 issue of Nature 

Genetics, showed a link between the 

gene for ABO blood type and pancreatic cancer. “We don’t understand the 

mechanism by which the ABO blood 

type influences pancreatic cancer 

risk, but the association is robust,” Dr. 

Stolzenberg-Solomon observed. The 

data are consistent with findings from 

small studies in the 1950s and 1960s 

and with recent data from the Nurses’ 

Health Study and Health Professionals’ 

Follow-Up Study indicating that subjects 

with type O blood have a lower risk of 

pancreatic cancer than subjects with 

other blood types. “The differing ABO 

blood group frequencies across populations may exist because of evolutionary 

processes,” Dr. Stolzenberg-Solomon 

noted. “In that regard, a specific blood 

type would suggest a selective advantage, 

such as resistance against infection.” The 

GWAS and its rapid replication included 

more than 4,000 cases and 4,000 controls from 12 cohort studies and 8 

case-control studies. “No cohort or 

case-control study could accomplish this 

alone,” Dr. Stolzenberg-Solomon stated. 

“PanScan is a multidisciplinary team 

effort that involves many investigators 

working together. Most epidemiologists 

interested in studying pancreatic cancer 

in the United States and Europe have 

contributed to this work.” 

Dr. Stolzenberg-Solomon has authored 

or co-authored 70 peer-reviewed manuscripts and mentors graduate students 

and postdoctoral fellows. Additionally, 

she serves on the editorial boards of the 

American Journal of Epidemiology and 

Cancer Epidemiology, Biomarkers & 

Prevention. Dr. Stolzenberg-Solomon 

also holds a position as an adjunct 

associate professor at the Yale School 

of Public Health and is a fellow of the 

American College of Epidemiology.

Within the Pancreatic Cancer Cohort 

Consortium, Dr. Stolzenberg-Solomon 

and her colleagues have conducted several studies and are planning several 

Rachael Stolzenberg-Solomon
March 2010 11

more. The group’s second GWAS on 

all of the participants recently identified susceptibility loci on chromosomes 

1q32.1, 13q22.1, and 5p15.33. The latter 

maps to a region that includes the TERT 

gene that has also been linked to other 

cancers, including brain, lung, and bladder cancers; melanoma; and leukemia. 

The scientists are conducting candidate 

gene pathway analyses using data from 

the two scans and are planning another 

GWAS that Dr. Stolzenberg-Solomon 

hopes will include an additional 1,500 

new cases from the NCI Cohort Consortium. Dr. Stolzenberg-Solomon also 

would like to further investigate the 

association of pancreatic cancer with 

folate deficiency, a topic of her dissertation work, in collaboration with the 

European Prospective Investigation into 

Cancer and Nutrition (EPIC) team.

Dr. Stolzenberg-Solomon has won 

several awards in recognition of her 

contributions to cancer research, 

including a 2008 NIH Merit Award 

for sustained and innovative work 

in elucidating nutritional, genetic, 

infectious, and other determinants 

of pancreatic cancer. 

Before obtaining her M.P.H. and Ph.D. 

degrees, she received a B.S. in dietetics 

from the University of California, 

Davis and an M.Ed. in nutrition from 

Vanderbilt University. She currently 

represents the Alpha-Tocopherol, 

Beta-Carotene Cancer Prevention 

(ATBC) Cohort Study for pancreatic 

cancer–related analyses in the Harvard 

Pooling Project on Prospective Studies 

of Diet and Cancer, and she serves on 

the steering committee for the cohort 

and case-control consortia on studies 

of pancreatic cancer.

Throughout her career at NCI—from 

predoctoral fellow to her current position as a tenure-track investigator—

Dr. Stolzenberg-Solomon has contributed enormously to pancreatic cancer 

research. She remains committed to 

finding answers to the many questions 

surrounding pancreatic cancer, while 

simultaneously maintaining a happy 

and fulfilling family life with her husband and two young children. n

—Maria Sgambati, M.D.

I

n October, DCEG members participated in 

the 22nd annual NIH Research Festival. This 

event features the achievements of intramural 

scientists at NIH and provides an opportunity for 

NIH-affiliated scientists to explore the breadth 

and depth of research conducted across the 

Intramural Research Program. 

Alisa M. Goldstein, Ph.D., Genetic Epidemiology Branch (GEB), chaired a symposium titled 

Finding Additional High-risk Susceptibility Genes: 

Problems and Solutions. At the symposium, 

Rose Yang, Ph.D., M.P.H. (GEB), presented 

“Identification of major susceptibility genes using 

combined linkage and array-CGH analyses.” 

Poster presentations included:

William F. Anderson, M.D., M.P.H., Biostatistics Branch (BB), Male breast cancer: A 

population-based comparison with female 

breast cancer 

DCEG Investigators Participate In the NIH Research Festival

Joseph Boland and Victor Lonsberry, both of 

the Core Genotyping Facility, Alternate multiplex 

process increases flexibility of the Fluidigm integrated fluidic circuits single nucleotide polymorphism genotyping platform

Porcia T. Bradford, M.D. (GEB), Increased 

risk of secondary primary cancers after diagnosis 

of melanoma

Charles Chung, Ph.D., Laboratory of Translational Genomics (LTG), Fine-mapping of the prostate cancer locus on chromosome 11q13 reveals 

three independent common variants in CGEMS 

(Cancer Genetic Markers of Susceptibility) 

Linda Dong, Ph.D., Occupational and Environmental Epidemiology Branch (OEEB), Urinary 

prostaglandin E2 metabolite and gastric cancer 

risk in the Shanghai Women’s Health Study 

Sara Karami, Ph.D. (OEEB), Family history of 

cancer and renal cell cancer risk in Caucasians 

and African Americans 

Idan Menashe, Ph.D. (BB), Pathway analysis 

of breast cancer genome-wide association study 

(GWAS) highlights three pathways and two 

canonical signaling cascades 

Hemang Parikh, Ph.D. (LTG), A comprehensive 

resequence analysis of the KLK15-KLK3-KLK2 

locus on chromosome 19q13.33 

Scott Quinlan, M.S., Infections and Immunoepidemiology Branch, Spectrum of hematologic 

malignancies associated with solid organ transplantation: Results of a U.S. population-based 

case-control study 

Figure 1. Manhattan plot of the p value results 

from the second pancreatic cancer GWAS 

(PanScan2) adjusted for sex, age, and population 

stratification.

Chromosome

12

10

8

7

6

5

4

3

2

1

0

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 1920 2122 X

–log10(p)

1q32

5p15 9q34

13q22
DCEG Linkage 12

“We have spent more than 10 

years searching for the genes 

implicated in familial chordoma,” stated 

Xiaohong Rose Yang, Ph.D., M.P.H., 

an investigator in DCEG’s Genetic Epidemiology Branch (GEB). Dr. Yang is 

the first author of an article published 

in the November 2009 issue of Nature 

Genetics that identifies the duplication 

of a specific gene as a major susceptibility factor for familial chordoma, a rare 

form of bone tumor. “New technology 

that complemented our traditional 

gene-mapping strategy enabled us to 

make this critical discovery.” 

Using this new technology—high-resolution array-based comparative genomic 

hybridization (array-CGH)—Dr. Yang 

and her colleagues analyzed the entire 

human genome of members of chordoma-affected families to identify unique 

variations in the number of gene copies 

present. The researchers found duplicated DNA in chromosome region 6q27 

in all chordoma-affected subjects among 

four chordoma families. The duplicated region contained only one known 

gene, T (brachyury), which is expressed 

specifically in cells from which chordoma 

is believed to originate. “We feel great 

satisfaction in having finally identified 

the gene after years of research,” Dr. Yang 

said. “Importantly, our study demonstrates that rare copy number variations 

(CNVs), in addition to small sequence 

changes, can play an important role in 

the development of cancer.”

Dr. Yang came to the United States 

to receive a Ph.D. in physiology from 

Georgetown University Medical Center 

after receiving an M.S. in cell biology at Beijing Normal University in 

China. Her interest in epidemiology led 

her to GEB as a postdoctoral fellow in 

2000, during which time she received 

an M.P.H. from the Johns Hopkins 

Bloomberg School of Public Health. 

Since 2006, Dr. Yang has been a tenuretrack investigator and has continued 

working on projects that expand on 

her postdoctoral research.

Dr. Yang believes that the identification of susceptibility genes for rare 

familial cancers, such as chordoma, 

might lead to the identification of 

new genes or pathways that play a role 

in more common cancers. Studying 

cancers with known hereditary links 

also helps researchers discern the 

differences between the contributions 

of genes and environment.

The genetic alteration that Dr. Yang 

found in chordoma has proven to be 

an interesting twist in cancer susceptibility. The discovery that an inherited 

duplication of a gene, rather than small 

sequence changes, is responsible for the 

development of a familial form of cancer is an important finding in the field. 

Dr. Yang said, “Although it is not clear 

how frequent and through what mechanism CNVs could influence cancer, it is 

possible that this type of variant is much 

more common in cancer than originally 

thought.”

Dr. Yang is applying the techniques 

successfully used in the study of chordoma to determine whether CNVs may 

contribute to susceptibility to other 

inherited cancers, such as cutaneous 

malignant melanoma. She is employing 

new technologies in addition to arrayCGH, such as exome sequencing, to 

enhance her search for genes linked 

to cancer susceptibility. 

Rose Yang Seeks and Finds Cancer Susceptibility Genes

Rose Yang

Patricia Hartge, Sc.D., Epidemiology and 

Biostatistics Program, and Mary H. Ward, 

Ph.D., Occupational and Environmental Epidemiology Branch, have been elected as DCEG’s new 

Women Scientists Advisor (WSA) and WSA-Alternate, respectively. They are replacing outgoing WSA 

Ann W. Hsing, Ph.D., Hormonal and Reproductive 

Epidemiology Branch. During her three-year term as 

WSA, Dr. Hsing led many special initiatives, including 

a time management course and brown bag meetings 

with visiting scientists. She served on DCEG’s Senior 

Advisory Group and on numerous search committees 

as well as worked with the Center for Cancer Research representatives to develop new WSA 

mentoring and leadership awards. DCEG Director Joseph F. Fraumeni, Jr., M.D., thanks Dr. Hsing 

for her dedicated service and welcomes Drs. Hartge and Ward in their new roles.

New WSA Representatives

New WSA Representatives: Patricia Hartge 

and Mary Ward.
March 2010 13

As part of her research portfolio, Dr. 

Yang works with scientists in other 

branches of the Division. For example, 

Dr. Yang and researchers in the Hormonal and Reproductive Epidemiology 

Branch are using tissue microarray 

analysis to study the etiologic heterogeneity of breast cancer. By analyzing data 

from a large, population-based casecontrol study of breast cancer, the team 

found that some risk factors for breast 

cancer differ by tumor subtypes. Dr. 

Yang is currently expanding this work 

by analyzing data pooled by the Breast 

Cancer Association Consortium from 

34 studies of breast cancer. 

Dr. Yang also leads a study—in collaboration with scientists in the Radiation 

Epidemiology Branch and the NCI Center 

for Cancer Research—on the characterization of genomic alterations in radiation-related breast cancer. Using samples 

collected from the Childhood Cancer 

Survivor Study, Dr. Yang seeks to better 

understand breast cancer among patients 

who received high-dose radiation as a 

treatment for childhood cancers.

Dr. Yang has received numerous awards, 

including the NCI Director’s Intramural 

Innovation Award in 2007 and 2009 

for supplemental funds to support 

highly creative research. She credits 

the work environment at DCEG as 

part of her success. “I feel fortunate 

to have outstanding colleagues here 

at DCEG,” Dr. Yang noted. “Many of 

them have served as mentors. They 

have assisted me in making connections 

for research collaborations and finding 

appropriate resources to carry out 

my research.” n

—Amber K. Boehm, Ph.D.

PDE10A

T

PRR18

SFT2D1

BRO44L

UCSC reference genes

0.600 Family 1 0.400

0.200

0.000

-0.200

-0.400

-0.600

0.600

0.400

0.200

0.000

-0.200

-0.400

-0.600

0.600

0.400

0.200

0.000

-0.200

-0.400

-0.600

0.600

0.400

0.200

0.000

-0.200

-0.400

-0.600

165,960,000

165,980,000

166,000,000

166,020,000

166,040,000

166,060,000

166,080,000

166,100,000

166,120,000

166,140,000

166,160,000

166,180,000

166,200,000

166,220,000

166,240,000

166,260,000

166,280,000

166,300,000

166,320,000

166,340,000

166,360,000

166,380,000

166,400,000

166,420,000

166,440,000

166,460,000

166,480,000

166,500,000

166,520,000

166,540,000

166,560,000

166,580,000

166,600,000

166,620,000

166,640,000

166,660,000

166,680,000

166,700,000

166,720,000

Family 3

Family 4

Family 8

CNVs

chr6

Chr6 12 13 q21 27

Figure 1. Duplications of region 6q27 in chordoma cases from four chordoma-affected families by array-comparative genomic hybridization. T is the only gene 

located within the duplicated region. There is no previously reported copy number variation, indicated as a red bar, in this region. 
DCEG Linkage 14

Jack Cuzick Visits as an HREB Distinguished Lecturer

The Hormonal and Reproductive Epidemiology Branch (HREB) hosted 

Dr. Jack Cuzick in December as an HREB 

Distinguished Lecturer. Dr. Cuzick is the 

John Snow Professor of Epidemiology at 

Wolfson Institute of Preventive Medicine 

at Queen Mary, University of London 

and head of the Centre for Epidemiology, 

Mathematics, and Statistics at Cancer 

Research UK in London. He is internationally recognized for his contributions 

to cervical cancer screening and breast 

cancer chemoprevention.

During his visit, Dr. Cuzick presented 

a seminar titled “Chemoprevention of 

breast cancer: Risk factors and potential 

agents.” He argued that mammographic 

density may be the most important target for breast cancer prevention and that 

the key to prevention is identifying both 

high-risk women and non-toxic, effective preventive agents. Dr. Cuzick summarized the chemopreventive effects of 

aromatase inhibitors, tamoxifen, and 

raloxifene in randomized trials. In addition, he described his recent findings 

from the International Breast Cancer 

Intervention Study (IBIS-I), a trial of 

tamoxifen for breast cancer prevention, 

which showed a change in mammographic density as a biomarker of risk 

reduction. Dr. Cuzick is currently leading IBIS-II, a large international breast 

cancer prevention trial that continues 

the work of IBIS-I. The trial, which is 

recruiting participants through 2011, 

will compare the aromatase inhibitor 

anastrozole with tamoxifen. Dr. Cuzick 

concluded his presentation by emphasizing that in addition to developing 

early detection technologies, future 

research should focus on prevention 

strategies that alter the natural history 

of breast cancer.

Following the seminar, Dr. Cuzick 

held a lunch discussion with DCEG 

fellows that focused on early career 

development. His advice for fellows 

was to: (1) become an expert in a single 

cancer, (2) try to answer the major 

health problems, even if it takes a long 

time, (3) identify and work in areas 

that are understudied, (4) acquire a 

specialist skill that is in short supply, 

and (5) strive to be the best. 

Dr. Cuzick also participated in a series 

of roundtable discussions moderated by 

HREB investigators. Mark E. Sherman, 

M.D., led a session on breast cancer 

precursors and pathology; Philip E. 

Castle, Ph.D., M.P.H., and Nicolas 

Wentzensen, M.D., Ph.D., facilitated 

a discussion related to cervical cancer 

screening for low- and high-resource 

settings; Ann W. Hsing, Ph.D., moderated a session on prostate cancer screening and etiologic research; and Gretchen 

L. Gierach, Ph.D., facilitated a session 

on mammographic density as a “breast 

biosensor.” n

—Gretchen L. Gierach, Ph.D.

Jack Cuzick receives HREB Distinguished Lecture poster 

from Branch Chief Louise Brinton.

DCEG researchers participated in the seventh international conference of the African 

Organisation for Research and Training in Cancer (AORTIC) held in Dar Es Salaam, 

Tanzania in November. The theme of the conference, Cancer in Africa – the New Reality, 

focused on all aspects of cancer care and management, from prevention and diagnosis to 

treatment and palliation. Special emphasis was given to cancers with unique incidence patterns, 

including HIV-associated cancers, cervical cancer, Kaposi sarcoma, and Burkitt’s lymphoma, 

as well as cancers that often are detected at unusually late stages in Africa, such as breast 

and prostate cancers. 

Approximately 700 people attended the conference, including representatives from 36 African 

and 16 non-African countries. Louise A. Brinton, Ph.D., Chief of the Hormonal and Reproductive Epidemiology Branch, participated in the Methods in Clinical Cancer Research Workshop, 

sponsored by the American Society of Clinical Oncology (ASCO), and gave a presentation 

entitled “Good ideas, poor outcomes: Avoiding the pitfalls of epidemiologic research.” Sam M. 

Mbulaiteye, M.D., Infections and Immunoepidemiology Branch, held a stakeholders’ meeting 

for NCI’s Epidemiology of Burkitt’s Lymphoma in East African Children or Minors (EMBLEM) study 

with collaborators from Tanzania and Kenya. 

—Louise A. Brinton, Ph.D., and Sam M. Mbulaiteye, M.D.

Investigators Meet to Discuss 

Cancer in Africa
March 2010 15

parallels findings from a recent GWAS 

in Caucasians reported by Maria 

Teresa Landi, M.D., Ph.D., and Neil E. 

Caporaso, M.D., of the Genetic Epidemiology Branch. H. Dean Hosgood, 

III, Ph.D. (OEEB), presented a metaanalysis suggesting that the GSTM1 

null genotype plays a role in lung cancer 

etiology in Asian populations exposed 

to indoor combustion products of coal 

used for cooking and heating; this contrasts with the inconsistent findings 

for this genotype reported in studies 

among Caucasians. Stephen J. Chanock, 

M.D., Director of the Core Genotyping 

Facility and Chief of the Laboratory of 

Translational Genomics, reported on 

the current and future outlook of GWAS 

research studies. The meeting then 

focused on finalization of the protocol 

for the GWAS effort. Agreement was 

reached to include smoking women in 

the GWAS as well as data on epidermal 

growth factor receptor (EGFR) mutation status of tumors and survival. Study 

investigators agreed to incorporate a 

core environmental exposure questionnaire into the many studies that are 

still enrolling subjects for use in future 

analyses of gene-environment interactions. A coordinating committee with 

representatives from each participating 

study was established to further the goals 

of the consortium. n

—Qing Lan, M.D., Ph.D., M.P.H.

Consortium Forms to Study Lung Cancer in Asia

Most cases of lung cancer among 

East Asian women occur among 

never smokers; this high cancer rate suggests that genetic/environmental risk 

factors are involved. Qing Lan, M.D., 

Ph.D., M.P.H., and Nathaniel Rothman, M.D., M.P.H., M.H.S., both of the 

Occupational and Environmental Epidemiology Branch (OEEB), hosted investigators from mainland China, Taiwan, 

Singapore, Japan, and the Republic of 

Korea at a meeting at NCI in December 

to develop research plans to study the 

etiology of lung cancer among neversmoking women in Asia. Joseph F. 

Fraumeni, Jr., M.D., Division Director, 

provided introductory comments at 

the meeting and described this multinational effort as “a study that will be 

viewed as a landmark event in lung 

cancer research.”

The meeting opened with a discussion 

of the first planned consortia project, a 

genome-wide association study (GWAS) 

of lung cancer among never-smoking 

Asian women. This work follows 

genome-wide scans that were recently 

completed in Caucasian populations, 

primarily among smokers, and will 

provide an opportunity to determine 

whether variants previously identified 

in Western populations are also present in this population. Additionally, a 

GWAS among never-smoking women in 

Asia has the potential to identify unique 

genetic variants in this population, 

where risk is driven partially by environmental factors other than tobacco, such 

as in-home solid fuel use and oil fumes 

from cooking. Following this discussion, 

Dr. Lan summarized an initial GWAS 

replication effort that found a region in 

the TERT-CLPTM1L locus on chromosome 5p15 to be associated with risk 

of lung adenocarcinoma among neversmoking women in Asia. This result 

Britton Trabert, Ph.D., recently joined the Hormonal 

and Reproductive Epidemiology Branch (HREB) as a 

Sallie Rosen Kaplan Postdoctoral Fellow. NCI awards the Sallie Rosen Kaplan Fellowship for Women Scientists in Cancer 

Research through an annual competition among postdoctoral 

fellows applying to train in the NCI Intramural Research Program. Made possible by a bequest from Ms. Kaplan to the 

Foundation for NIH, the women scientists receive a supplement to their first-year stipend.

Dr. Trabert comes to HREB from the University of Washington 

School of Public Health, where she earned a Ph.D. in epidemiology under the guidance of Dr. Victoria L. Holt. Her dissertation research sought to identify risk factors for endometriosis. Previously, Dr. Trabert completed 

an M.S.P.H. in epidemiology at the Emory University Rollins School of Public Health and an M.S. 

in biostatistics from the University of Michigan School of Public Health. Within DCEG, Dr. Trabert 

will continue to pursue her interests in reproductive and life-course epidemiology by focusing on 

hormone-related tumors in both men and women. She has begun working with Katherine A. 

McGlynn, Ph.D., a senior investigator in HREB, to examine hormonal and genetic influences on 

the etiology of testicular cancer and other conditions associated with testicular dysgenesis syndrome. Toward this end, Dr. Trabert is analyzing data from the Servicemen’s Testicular Tumor Environmental and Endocrine Determinants (STEED) Study and the NIH Collaborative Perinatal Project. 

Dr. Trabert has also begun working with Louise A. Brinton, Ph.D., Chief of HREB, to examine risk 

factors for endometrial cancer and the cancer risks associated with infertility treatments.

Britton Trabert

New Sallie Rosen Kaplan Fellow 
DCEG Linkage 16

An Update on the InterLymph Consortium

The InterLymph Consortium Eighth 

Annual Meeting was held in July 

at the University of British Columbia 

(UBC) in Vancouver. Formed in 2001, 

the InterLymph Consortium is an international group of investigators who conduct case-control studies of non-Hodgkin 

lymphoma (NHL). Consortium members 

discuss research, undertake projects that 

pool data across studies, and participate 

in collaborative research. This year’s 

meeting included sessions to develop specific collaborative projects, including new 

consortia for Hodgkin lymphoma (HL) 

and multiple myeloma (MM) research. 

Sixty-nine researchers from 13 countries 

attended meeting workshops. Martha S. 

Linet, M.D., M.P.H., Chief of the Radiation Epidemiology Branch, and Patricia 

Hartge, Sc.D., Epidemiology and Biostatistics Program, received awards for their 

outstanding service and their roles in 

founding the InterLymph Consortium. 

Nathaniel Rothman, M.D., M.P.H., 

M.H.S., Occupational and Environmental Epidemiology Branch, and Stephen 

J. Chanock, M.D., Director of the Core 

Genotyping Facility and Chief of the 

Laboratory of Translational Genomics, 

organized and cochaired a two-day 

meeting of researchers who are collaborating on a genome-wide association 

study (GWAS) of NHL. Discussions 

included whether to scan all cases versus histological subtypes, replication 

strategies, IRB requirements and NIH 

policies, DNA specifications, statistical 

approaches to analyses, and opportunities to leverage data on controls from 

previous GWAS scans. Participants 

agreed to supplement the etiologic study 

with a survival component. The group 

also established a GWAS Coordination 

Committee to include representatives 

from each participating NHL study as 

well as a publications subcommittee 

and an analysis working group. 

Working groups laid out plans for geneenvironment analyses to include evaluation of autoimmune factors, tobacco use, 

hair dye use, body mass index, height, 

familial occurrence, and occupational 

and environmental history as well as 

analyses of risk factors for rare NHL subtypes and survival. Dr. Christine Skibola 

of the University of California, Berkeley discussed InterLymph governance, 

including the project proposal and membership application process. Since the 

last InterLymph meeting in Australia, 

two major efforts were launched. First, 

a data coordinating center, established 

under the leadership of Dr. Susan Slager 

of the Mayo Clinic, provides centralized, 

well-documented approaches for combining datasets, creates a comprehensive 

data dictionary, develops core variables, 

and provides assistance and guidance on 

the more complex statistical analyses. 

Second, an InterLymph survey, for which 

Dr. Slager provided preliminary results, 

was conducted to provide information 

on cases with specific histopathological 

subtypes, genotyping efforts, specific 

genetic pathways, and variables from 

individual studies. 

The HL Working Group meeting—

co-led by Dr. Wendy Cozen of the 

University of Southern California, 

Dr. Sally Glaser of the Northern 

California Cancer Center, and Dr. 

Henrik Hjalgrim of the Statens Serum 

Institute—included presentations on a 

new susceptibility gene for HL, cytokine 

profiles in prediagnostic serum samples, 

and variations in methylation in twins 

discordant for HL. New studies are 

planned, and two pooling projects will 

soon be ending. The working group also 

plans to write a position paper on HL 

and Epstein-Barr virus. 

The MM Working Group, led by Dr. 

Brenda Birmann of Brigham and 

Women’s Hospital and Harvard Medical 

School, included presentations on the 

role of monoclonal gammopathy of 

undetermined significance and other 

risk factors. The working group also 

discussed plans for a member survey 

to ascertain data available for pooled 

collaborative studies to identify genetic 

susceptibility, lifestyle and environmental exposures, and gene-environment 

interactions.

Dr. John Spinelli, UBC, and Dr. Angela 

Brooks-Wilson, Simon Fraser University, 

organized the meeting. The next InterLymph Annual Meeting will be held in 

Washington, DC in April 2010. n

—Annelie M. Landgren, M.P.H. 

InterLymph Consortium Eighth Annual Meeting participants. (Photograph credit: Neil Edwardson, 

Arthur Edwardson Photography)
March 2010 17

Cohort Consortium Convenes Annual Meeting

I

nvestigators representing 39 cohort 

studies from the United States and 

abroad came together in Bethesda, 

Maryland in November for the NCI 

Cohort Consortium’s annual meeting. 

Joseph F. Fraumeni, Jr., M.D., DCEG 

Director, and Dr. Robert Croyle, Director of NCI’s Division of Cancer Control 

and Population Sciences (DCCPS), 

welcomed the participants and congratulated the group on 10 years of 

ground-breaking research that has combined the rapid advances in genomics 

with the power of rigorously designed 

cohort studies. Co-founder Robert N. 

Hoover, M.D., Sc.D., Director of the 

Epidemiology and Biostatistics Program 

(EBP), recognized outgoing chair Patricia Hartge, Sc.D. (EBP), for her years of 

leadership and service. He congratulated 

her successor, Dr. Michael Thun of the 

American Cancer Society, and welcomed 

new secretariat member Dr. Julie Buring of Brigham and Women’s Hospital 

and Harvard Medical School. He also 

thanked Geoffrey Tobias, Human 

Genetics Program, for his work as communications coordinator and welcomed 

Scott Rogers of DCCPS to the secretariat 

as NCI cohort liaison. 

Dr. Hartge provided an overview of 

the past year, citing the progress made 

in the consortium’s many initiatives, 

including the activities of four major 

projects: the Breast and Prostate Cancer 

Cohort Consortium (BPC3) identified 

genetic variants related to each cancer, 

published extensively, and launched a 

genome-wide association study (GWAS) 

of estrogen receptor–negative breast 

cancer and advanced prostate cancer; 

the Pancreatic Cancer Cohort Consortium (PanScan) identified variants in 

the ABO blood type gene and several 

other loci related to cancer risk, quantified risks associated with other factors, 

and explored the joint effects of genes 

and environment; the serum-based 

Vitamin D Pooling Project (VDPP) 

submitted results on six cancers for 

publication en bloc; and the results 

from the Obesity and Mortality Pooling Project will be submitted for publication shortly. 

Stephen J. Chanock, M.D., Director 

of the Core Genotyping Facility and 

Chief of the Laboratory of Translational 

Genomics, chaired a scientific panel 

discussion devoted to future directions in genomic studies. Presentations 

included a talk on integrated analyses 

of quantitative trait loci in neurological 

disease; an overview of the “ClinSeq” 

pilot project, which correlates genetic 

risk variants with disease phenotypes; 

and an examination of the difficulties in finding a genetic basis for some 

highly heritable traits. Some of the participants suggested that gene-gene or 

gene-environment interactions might 

obscure associations using GWAS, even 

in large-scale studies that include the 

NCI Cohort Consortium. 

The second plenary session focused on 

biobanking, proteomics, and biomarkers. Participants discussed several topics, including how future cohort studies 

could employ biospecimens to bridge 

the gap between population and disease cohorts and use well-characterized 

biomarkers to inform therapeutic interventions; the promise of proteomics for 

such applications as identifying early 

detection markers; and key features of 

population biobank projects that the 

consortium could undertake, such as 

studies of rare cancers, use of highdensity data (e.g., genomics, proteomics, 

metabolomics), and areas of pressing 

public health concern (e.g., the role 

of folate in cancer development). The 

meeting ended with a strategic planning 

workshop. 

To learn more about the Cohort Consortium, including its research and 

working groups, go to http://epi.grants.

cancer.gov/Consortia/cohort.html. n

—Patricia Hartge, Sc.D., 

and Alexandra Ekblom, M.P.H.

Secretariat Members: (front) Robert Croyle, Joseph Fraumeni, and Robert Hoover; (back) Nonye Harvey, 

Michael Thun, Patricia Hartge, Julie Palmer, Deborah Winn, Anne Zeleniuch-Jacquotte, Julie Buring, and 

James Cerhan. (Photograph credit: Keith Richardson)
DCEG Linkage 18

SCIENTIFIC HIGHLIGHTS

BLADDER CANCER

DNA Repair Genes and Smoking 

To study the roles of smoking and DNA 

repair genes as risk factors for bladder cancer, meta- and pooled analyses 

were conducted as part of the International Consortium of Bladder Cancer. 

The results included data on 10 single 

nucleotide polymorphisms (SNPs) 

corresponding to 7 DNA repair genes 

among 5,282 cases and 5,954 controls 

of non-Latino, white origin. Weak but 

consistent associations were observed 

with ERCC2 D312N (rs1799793, perallele odds ratio [OR] = 1.10), NBN 

E185Q (rs1805794, per-allele OR = 1.09), 

and XPC A499V (rs2228000, per-allele 

OR = 1.10). The association with NBN 

E185Q was limited to ever smokers and 

was strongest for the highest levels of 

smoking dose and smoking duration. 

(Stern MC, Lin J, Figueroa JD, Kelsey KT, Kiltie 

AE, Yuan JM, Matullo G, Fletcher T, Benhamou 

S, Taylor JA, Placidi D, Zhang ZF, Steineck G, 

Rothman N, Kogevinas M, Silverman D, Malats 

N, Chanock S, Wu X, Karagas MR, Andrew AS, 

Nelson HH, Bishop DT, Sak SC, Choudhury A, 

Barrett JH, Elliot F, Corral R, Joshi AD, GagoDominguez M, Cortessis VK, Xiang YB, Gao YT, 

Vineis P, Sacerdote C, Guarrera S, Polidoro S, 

Allione A, Gurzau E, Koppova K, Kumar R, Rudnai 

P, Porru S, Carta A, Campagna M, Arici C, Park 

SS, Garcia-Closas M, International Consortium 

of Bladder Cancer. Polymorphisms in DNA repair 

genes, smoking, and bladder cancer risk: Findings from the International Consortium of Bladder Cancer. Cancer Res 2009;69:6857–6864)

Rising Trend in Smoking-induced Tumors

The authors studied bladder cancer risk 

in relation to smoking using interview 

data from a population-based, casecontrol study conducted in Maine, New 

Hampshire, and Vermont from 2001 to 

2004 among 1,170 urothelial carcinoma 

patients and 1,413 controls. The study 

examined changes in smoking-induced 

bladder cancer risk over time by comparing ORs from New Hampshire residents 

in this study with those from two earlier 

case-control studies conducted there 

(see Figure 1). Regular and current cigarette smokers had higher risks of bladder cancer than never smokers (regular 

smokers, OR = 3.0; current smokers, 

OR = 5.2). There was an increasing trend 

in smoking-related risks over three consecutive periods (1994–1998, 1998–2001, 

and 2002–2004) among former smokers 

(OR = 1.4, 2.0, and 2.6, respectively) and 

current smokers (OR = 2.9, 4.2, and 5.5, 

respectively). Within categories of intensity, ORs increased approximately linearly with increasing pack-years smoked, 

but the slope of the increasing trend 

for smoking-related risks declined with 

increasing intensity. Based on modeling 

of pack-years and intensity, with equal 

pack-years of cigarettes smoked, smoking fewer cigarettes over a long time 

appeared more harmful than smoking 

more cigarettes over a shorter time. 

(Baris D, Karagas MR, Verrill C, Johnson A, 

Andrew AS, Marsit CJ, Schwenn M, Colt JS, 

Cherala S, Samanic C, Waddell R, Cantor KP, 

Schned A, Rothman N, Lubin J, Fraumeni JF Jr, 

Hoover RN, Kelsey KT, Silverman DT. A casecontrol study of smoking and bladder cancer 

risk: Emergent patterns over time. J Natl Cancer 

Inst 2009;101:1553–1561) 

BRAIN TUMORS

Height, Body Mass Index, 

and Physical Activity

Height, body mass index (BMI), and 

physical activity were studied in relation to glioma risk in the prospective 

NIH-AARP Diet and Health Study. 

10

Never smokers Current smokers

Smoking status

ORs and 95% CIs for bladder cancer 1

Former smokers

1.0 1.0 1.0

1.4

2.0

2.6

2.9

4.2

5.5

Figure 1. Trends in smoking-induced bladder cancer in New Hampshire from 1994 to 2004. Odds ratios 

(ORs) and 95% confidence intervals (CIs) for bladder cancer are shown for former and current smokers 

in New Hampshire during three consecutive time intervals: from July 1, 1994, to June 30, 1998 (372 case 

patients and 456 control subjects) (red bars); from July 1, 1998, to December 31, 2001 (324 case patients 

and 328 control subjects) (light gray bars); and from January 1, 2002, to December 31, 2004 (253 case 

patients and 199 control subjects) (light red bars), compared to never smokers. (Baris D, et al. 2009)
March 2010 19

to lessen the carcinogenic effects of 

breast irradiation. (Inskip PD, Robison LL, 

Stovall M, Smith SA, Hammond S, Mertens AC, 

Whitton JA, Diller L, Kenney L, Donaldson SS, 

Meadows AT, Neglia JP. Radiation dose and 

breast cancer risk in the childhood cancer 

survivor study. J Clin Oncol 2009;27:3901–3907)

GENETICS

Familial Chordoma 

Using high-resolution, array-comparative 

genomic hybridization analysis, the 

authors identified unique duplications 

of a region on chromosome 6q27 in four 

multiplex families with at least three 

cases of chordoma, a cancer of presumed 

notochordal origin. The duplicated 

region contains only the T (brachyury) 

gene, which is important in notochord 

development and is expressed in most 

sporadic chordomas. These findings 

highlight the value of screening for 

complex genomic rearrangements in 

searches for cancer susceptibility genes. 

(Yang XR, Ng D, Alcorta DA, Liebsch NJ, 

Sheridan E, Li S, Goldstein AM, Parry DM, 

Kelley MJ. T (brachyury) gene duplication confers major susceptibility to familial chordoma. 

Nat Genet 2009;41:1176–1178)

A New Statistic for Genome-wide 

Association Studies

Aggregate results from genome-wide 

association studies (GWAS), such as 

genotype frequencies for cases and 

controls, were often made available on 

public web sites until recently due to 

an assumption that such results disclosed negligible personal information. 

A recent study suggested that a method 

for forensic detection of an individual’s 

contribution to an admixed DNA sample 

could be applied to aggregate GWAS data 

(Homer N, et al. Resolving individuals 

contributing trace amounts of DNA to 

highly complex mixtures using highdensity SNP genotyping microarrays. 

PLoS Genet 2008;4:e1000167). Using a 

likelihood-based statistical framework, 

Participants completed a baseline questionnaire sent in 1995–1996 inquiring 

about height, weight, and potential confounders. A second questionnaire sent 

in 1996 inquired about physical activity 

at ages 15–18, 19–29, and 35–39 years, 

as well as during the past 10 years, and 

weight at ages 18, 35, and 50 years. 

During follow-up through 2003, 480 

cases of glioma among 499,437 respondents to the baseline questionnaire and 

257 cases among 305,681 respondents 

to the second questionnaire were documented. Glioma risk among tall persons 

(> 1.90 m) was twice that of short persons (< 1.60 m) (multivariate relative 

risk [RR] = 2.12). Risk among participants who were obese (BMI 30.0–34.9 

kg/m2) at age 18 years was nearly four 

times that of persons of normal weight 

(BMI 18.5–24.9 kg/m2) at this age (RR = 

3.74). Risk among participants who were 

active during ages 15–18 years was 36% 

lower than that of persons who were 

inactive. BMI and physical activity after 

age 18 years were unrelated to glioma 

risk. Results support a role for early-life 

energy balance in glioma carcinogenesis. 

(Moore SC, Rajaraman P, Dubrow R, Darefsky 

AS, Koebnick C, Hollenbeck A, Schatzkin A, 

Leitzmann MF. Height, body mass index, and 

physical activity in relation to glioma risk. 

Cancer Res 2009;69:8349–8355)

BREAST CANCER

Müllerian Inhibiting Substance Levels

To examine whether serum Müllerian 

inhibiting substance (MIS) levels are 

associated with breast cancer risk, the 

authors conducted a prospective casecontrol study of 309 participants registered in the Columbia, Missouri Serum 

Bank. Each of 105 in situ or invasive 

breast cancer cases with prediagnostic 

serum collected before menopause was 

matched to two control subjects by age, 

date, menstrual cycle day, and time of 

day of blood collection. The relative 

ORs of breast cancer for women in 

increasing MIS quartiles were 1, 2.8, 5.9, 

and 9.8 (p < 0.001). The association was 

weaker in women who were not taking 

oral contraceptives at the time of blood 

collection, but adjustment for estradiol 

and testosterone levels did not materially alter results. The association of MIS 

with breast cancer did not vary by age at 

blood collection but was stronger among 

women diagnosed with breast cancer 

at an older age than among those diagnosed at a younger age. MIS may be a 

novel biomarker of increased breast cancer risk. (Dorgan JF, Stanczyk FZ, Egleston BL, 

Kahle LL, Shaw CM, Spittle CS, Godwin AK, Brinton LA. Prospective case-control study of serum 

Müllerian inhibiting substance and breast cancer 

risk. J Natl Cancer Inst 2009;101:1501–1509)

Risk Related to Childhood 

Cancer Treatments

Conducting a case-control study of 

breast cancer in a cohort of 6,647 women 

who were five-year survivors of childhood cancer treated during 1970–1986, 

the authors identified 120 patients with 

histologically confirmed breast cancer 

and matched each patient to four controls by age at and time since initial cancer. The OR for breast cancer increased 

linearly with radiation dose and reached 

11-fold for local breast doses of about 

40 Gy relative to no radiation. Risk 

associated with breast irradiation was 

sharply reduced among women who 

received 5 Gy or more to the ovaries. The 

excess OR per Gy was 0.36 for those who 

received ovarian doses less than 5 Gy 

and 0.06 for those who received higher 

doses. Radiation-related risk did not vary 

significantly by age at exposure. Use of 

dacarbazine, dactinomycin, doxorubicin, 

and carmustine showed borderline significantly elevated risks. Results confirm 

the radiation sensitivity of the breast in 

females ages 10–20 years old but do not 

show a strong effect of age at exposure 

within this range. Irradiation of the 

ovaries at doses of 5 Gy or greater seems 
DCEG Linkage 20

the authors developed an improved statistic that uses genotype frequencies and 

individual genotypes to infer whether 

a specific individual or any close relatives participated in the GWAS and, if 

so, the participant’s phenotype status. 

This statistic compares the logarithm 

of genotype frequencies, in contrast to 

that of Homer et al., which is based on 

differences in either SNP probe intensity 

or allele frequencies. The authors also 

derived the theoretical power of their 

test statistics and explored empirical 

performance in scenarios with varying numbers of randomly chosen or 

top-associated SNPs. (Jacobs KB, Yeager 

M, Wacholder S, Craig D, Kraft P, Hunter DJ, 

Paschal J, Manolio TA, Tucker M, Hoover RN, 

Thomas GD, Chanock SJ, Chatterjee N. A new 

statistic and its power to infer membership in a 

genome-wide association study using genotype 

frequencies. Nat Genet 2009;41:1253–1257)

HEAD AND NECK CANCERS

Smoking and Alcohol Consumption

The authors pooled data from 15 casecontrol studies and modeled the excess 

odds ratio (EOR) to assess the risks of 

laryngeal, pharyngeal, and oral cavity 

cancers by total cigarette smoke and 

alcohol exposure (pack-years and drinkyears) and the modification of risks 

by exposure rate (cigarettes/day and 

drinks/day). Above 15 cigarettes per day, 

the EOR per pack-year decreased with 

increasing cigarettes per day, suggesting 

that more cigarettes per day for a shorter 

duration was less deleterious than fewer 

cigarettes per day for a longer duration. 

Estimates of EOR per pack-year were 

homogeneous across sites, whereas the 

effects of cigarettes per day varied, indicating that the greater laryngeal cancer 

risk derived from differential cigarettes 

per day effects and not pack-years. EOR 

per drink-year estimates increased 

through 10 drinks per day, suggesting that greater drinks per day for a 

shorter duration was more deleterious 

than fewer drinks per day for a longer 

duration. EOR per drink-year estimates 

varied by site, whereas drinks per day 

effects were homogeneous, indicating 

that the greater pharyngeal and oral cavity cancer risk with alcohol consumption 

derived from the differential effects of 

drink-years and not drinks per day.

(Lubin JH, Purdue M, Kelsey K, Zhang ZF, Winn 

D, Wei Q, Talamini R, Szeszenia-Dabrowska N, 

Sturgis EM, Smith E, Shangina O, Schwartz SM, 

Rudnai P, Neto JE, Muscat J, Morgenstern H, 

Menezes A, Matos E, Mates IN, Lissowska J, 

Levi F, Lazarus P, La Vecchia C, Koifman S, 

Herrero R, Franceschi S, Wünsch-Filho V, 

Fernandez L, Fabianova E, Daudt AW, Maso LD, 

Curado MP, Chen C, Castellsague X, Brennan P, 

Boffetta P, Hashibe M, Hayes RB. Total exposure 

and exposure rate effects for alcohol and smoking and risk of head and neck cancer: A pooled 

analysis of case-control studies. Am J Epidemiol

2009;170:937–947)

KIDNEY CANCER

Apolipoprotein E/C1 Locus Variants

The investigators genotyped 635 SNPs in 

38 candidate lipid peroxidation genes in 

777 Caucasian renal cell carcinoma cases 

and 1,035 controls enrolled in a large 

European study. Top candidate SNPs 

were confirmed among 718 Caucasian 

cases and 615 controls in a second study 

in the United States. Two of the three 

SNPs (rs8106822 and rs405509) that 

replicated in the U.S. study were within 

a regulatory region of the APOE promoter. The ORs for the rs8106822 

A>G variant were 1.22AG and 1.41GG

in the European study, 1.05AG and 1.51GG

in the U.S. study, and 1.15AG and 1.44GG

among 1,485 cases and 1,639 controls 

combined. The rs405509 G>T variant 

was inversely associated with risk of kidney cancer in the European study (OR 

= 0.87TG, 0.71TT), the U.S. study (OR = 

0.68TG, 0.71TT), and both studies combined (OR = 0.79TG, 0.71TT), as was the 

G-G haplotype (r2 = 0.64, p = 4.7 x 10–4). 

This association is biologically plausible 

because SNP rs405509 was shown to 

modify protein binding and transcriptional activity of the APOE protein in 

vitro and is in linkage disequilibrium 

with key known variants defining the 

e2, e3, and e4 alleles that modify risk of 

atherosclerosis, Alzheimer’s disease, and 

progression of HIV infection to AIDS.

(Moore LE, Brennan P, Karami S, Menashe I, 

Berndt SI, Dong LM, Meisner A, Yeager M, 

Chanock S, Colt J, Schwartz K, Davis F, Zaridze 

D, Mattveev V, Janout V, Kollarova H, Bencko V, 

Navratilova M, Szeszenia-Dabrowska N, Mates 

D, Holcatova I, Boffetta P, Chow WH, Rosenberg 

PS, Rothman N. Apolipoprotein E/C1 locus variants modify renal cell carcinoma risk. Cancer 

Res 2009;69:8001–8008)

Sara Schonfeld Successfully Defends 

Dissertation

I

n September, Sara Schonfeld, Ph.D., Radiation Epidemiology Branch (REB), successfully 

defended her doctoral dissertation at the Johns Hopkins Bloomberg School of Public Health. 

She conducted research for her thesis, “Hormonal factors and the risk of breast and endometrial 

cancers among postmenopausal nulliparous women,” under the mentorship of Dr. Kala Visvanathan of Johns Hopkins; Amy Berrington de Gonzalez, D.Phil. (REB); Patricia Hartge, Sc.D.,

Epidemiology and Biostatistics Program; Dr. James Lacey, Jr., formerly of the Hormonal and 

Reproductive Epidemiology Branch; and Ruth M. Pfeiffer, Ph.D., Biostatistics Branch. Dr. 

Schonfeld will work as a postdoctoral fellow in REB with Elaine Ron, Ph.D., and Ethel S. 

Gilbert, Ph.D., on studies of radiation dose and cancer mortality in populations affected by 

activities at the Mayak Nuclear Facility in Russia as well as several other studies in the branch.
March 2010 21

Fish, Vitamin D, and Flavonoids 

Investigators assessed whether fish, vitamin D, and flavonoid intake affected 

prospective risk of renal cell cancer 

among 27,111 male smokers in the 

Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Among 

228 cases, risk (quartile 4 vs. quartile 1) 

was reduced for the flavonoid quercetin 

intake (hazard ratio [HR] = 0.6) and 

increased for Baltic herring intake (HR 

= 2.0), with adjustment for age, BMI, 

smoking, blood pressure, alcohol use, 

physical activity, urban residence, and 

education. In geographically stratified 

models, the risks associated with herring and total fish intake appeared to 

be highest in the urban coast region, 

although the interaction was not statistically significant. (Wilson RT, Wang J, Chinchilli 

V, Richie JP, Virtamo J, Moore LE, Albanes D. 

Fish, vitamin D, and flavonoids in relation to renal 

cell cancer among smokers. Am J Epidemiol 

2009;170:717–729)

LEUKEMIA

Precursor Immunoglobulin Abnormalities 

Among 77,469 participants with serially collected serum samples in the 

prospective Prostate, Lung, Colorectal 

and Ovarian (PLCO) Cancer Screening 

Trial, the authors identified 109 persons 

who developed chronic lymphocytic 

leukemia (CLL). The authors then evaluated the presence and temporal patterns 

of monoclonal (M)-proteins, kappa and 

lambda free light chains (FLCs), and 

hypogammaglobulinemia in serum from 

blood obtained up to 9.8 years before 

CLL diagnosis (see Figure 2). The prevalence of an abnormal FLC ratio, Mprotein, and hypogammaglobulinemia 

before CLL diagnosis was 38%, 13%, 

and 3%, respectively. M-proteins and 

abnormal FLC ratios were detected up 

to 9.8 years before CLL diagnosis in 48 

persons (44%). Hypogammaglobulinemia was not present until three years 

before the diagnosis of CLL. Among 

37 patients with information on tumor 

Figure 2. Year-by-year prevalence of an abnormal free light chain (FLC) ratio, monoclonal (M)-protein, 

and hypogammaglobulinemia (gamma) among 109 chronic lymphocytic leukemia (CLL) patients. 

(Tsai HT, et al. 2009)

35

30

25

20

15

10

5

0

10 9 8 7 6 5 4 3 2 1

Years prior to CLL diagnosis

Prevalence (%)

Condition = abnormal FLC ratio

Condition = M-protein

Condition = gamma

cell immunophenotype, an association between immunophenotype and 

involved FLC (p = 0.024, Fisher exact 

test) was observed. Among 61 persons 

with a normal FLC ratio and without 

an M-protein, 17 had elevated kappa or 

lambda FLC levels, indicating polyclonal 

B-cell activation. Findings support a role 

for chronic immune stimulation in CLL 

genesis. (Tsai HT, Caporaso NE, Kyle RA, 

Katzmann JA, Dispenzieri A, Hayes RB, Marti 

GE, Albitar M, Ghia P, Rajkumar SV, Landgren O. 

Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic 

lymphocytic leukemia: A prospective study. 

Blood 2009;114:4928–4932) 

LUNG CANCER

GWAS by Histologic Type

The authors conducted a GWAS of lung 

cancer and its major histologic types, 

genotyping 515,922 SNPs in 5,739 lung 

cancer cases and 5,848 controls from one 

population-based, case-control study 

and three cohort studies. Results were 

combined with summary data from 10 

additional studies, for a total of 13,300 

cases and 19,666 controls of European 

descent. Four studies also provided 

histology data for replication, resulting in 3,333 adenocarcinomas (AD), 

2,589 squamous cell carcinomas, and 

1,418 small cell carcinomas. In analyses by histology, rs2736100 (TERT) on 

chromosome 5p15.33 was associated 

with AD risk (OR = 1.23) but not with 

other histologic types. This finding was 

confirmed in each replication study and 

overall meta-analysis (OR = 1.24 for 

AD). Other previously reported association signals on 15q25 and 6p21 were also 

refined, but no additional loci reached 

genome-wide significance. (Landi MT, 

Chatterjee N, Yu K, Goldin LR, Goldstein AM, 

Rotunno M, Mirabello L, Jacobs K, Wheeler W, 

Yeager M, Bergen AW, Li Q, Consonni D, Pesatori 

AC, Wacholder S, Thun M, Diver R, Oken M, 

Virtamo J, Albanes D, Wang Z, Burdette L, 

Doheny KF, Pugh EW, Laurie C, Brennan P, 

Hung R, Gaborieau V, McKay JD, Lathrop M, 
DCEG Linkage 22

McLaughlin J, Wang Y, Tsao MS, Spitz MR, 

Wang Y, Krokan H, Vatten L, Skorpen F, Arnesen 

E, Benhamou S, Bouchard C, Metsapalu A, 

Vooder T, Nelis M, Välk K, Field JK, Chen C, 

Goodman G, Sulem P, Thorleifsson G, Rafnar T, 

Eisen T, Sauter W, Rosenberger A, Bickeböller 

H, Risch A, Chang-Claude J, Wichmann HE, 

Stefansson K, Houlston R, Amos CI, Fraumeni JF 

Jr, Savage SA, Bertazzi PA, Tucker MA, Chanock 

S, Caporaso NE. A genome-wide association 

study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet 2009;85:679–691)

NON-HODGKIN LYMPHOMA

Chronic B-cell Stimulation

To investigate among healthy persons 

whether serum concentration of soluble 

CD30 (sCD30), a marker for chronic 

B-cell stimulation, is associated with 

non-Hodgkin lymphoma (NHL) risk, 

a nested case-control study within 

the PLCO Cancer Screening Trial was 

conducted. A strong dose-response 

relationship was found between prediagnostic sCD30 concentration and NHL 

risk among 234 cases and individually matched controls (OR for second, 

third, and fourth quartiles vs. first 

quartile = 1.4, 2.2, 4.1, respectively; p 

< 0.001), which persisted among cases 

diagnosed 6–10 years after providing a 

blood sample. As a similar relationship 

has been observed among HIV-positive 

patients, chronic B-cell stimulation may 

be an important mechanism involved in 

B-cell lymphomagenesis in both severely 

immunocompromised and healthy populations. (Purdue MP, Lan Q, Martinez-Maza O, 

Oken MM, Hocking W, Huang WY, Baris D, Conde 

B, Rothman N. A prospective study of serum 

soluble CD30 concentration and risk of nonHodgkin lymphoma. Blood 2009;114:2730–2732)

PANCREATIC CANCER

Smoking-related Risks

Smoking effects were examined in the 

Pancreatic Cancer Cohort Consortium. 

When compared with never smokers, 

current smokers had a significantly 

elevated risk (OR = 1.77). Risk increased 

significantly with greater intensity (> 30 

cigarettes/day: OR = 1.75), duration 

(> 50 years: OR = 2.13), and cumulative 

smoking dose (> 40 pack-years: OR = 

1.78). Risk at more than 15 years after 

smoking cessation was similar to that 

for never smokers. Estimates of EOR 

per pack-year declined with increasing 

intensity, suggesting greater risk for total 

exposure delivered at lower intensity for 

longer duration than for higher intensity 

for shorter duration. Results suggest 

that smoking has a late-stage effect on 

pancreatic carcinogenesis. (Lynch SM, 

Vrieling A, Lubin JH, Kraft P, Mendelsohn JB, 

Hartge P, Canzian F, Steplowski E, Arslan AA, 

Gross M, Helzlsouer K, Jacobs EJ, LaCroix A, 

Petersen G, Zheng W, Albanes D, Amundadottir L, Bingham SA, Boffetta P, Boutron-Ruault 

MC, Chanock SJ, Clipp S, Hoover RN, Jacobs 

K, Johnson KC, Kooperberg C, Luo J, Messina 

C, Palli D, Patel AV, Riboli E, Shu XO, Rodriguez 

Suarez L, Thomas G, Tjønneland A, Tobias GS, 

Tong E, Trichopoulos D, Virtamo J, Ye W, Yu K, 

Zeleniuch-Jacquette A, Bueno-de-Mesquita HB, 

Stolzenberg-Solomon RZ. Cigarette smoking 

and pancreatic cancer: A pooled analysis from 

the Pancreatic Cancer Cohort Consortium. Am J 

Epidemiol 2009;170:403–413)

PROSTATE CANCER

Insulin, Glucose, and Insulin Resistance 

The authors assessed the relationships 

of levels of serum insulin, glucose, the 

molar ratio of insulin to glucose, and the 

homeostasis model assessment of insulin 

resistance (HOMA-IR) to the development of prostate cancer in a case-cohort 

study within the ATBC Study cohort 

of Finnish men. One hundred cases 

with incident prostate cancer and 400 

noncases from the larger cohort were 

studied. Fasting serum was collected 

5–12 years (average 9.2 years) before 

diagnosis. Insulin concentrations in fasting serum from case subjects were 8% 

higher than among noncase subjects, 

and the molar ratio of insulin to glucose 

and HOMA-IR were 10% and 6% higher 

in cases, respectively, but these differences were not statistically significant. 

Compared with insulin levels in the first 

quartile, those in the second through 

fourth insulin quartiles were associated 

with increasing risks of prostate cancer 

(OR = 1.50, 1.75, and 2.55, respectively; 

p = 0.02). A similar pattern was observed 

with the HOMA-IR (OR = 2.10, p = 

0.02) for the highest vs. lowest quartiles. 

The results of the first NIH Clinical Research Workshop on Dyskeratosis Congenita (DC) were 

reported by Sharon A. Savage, M.D., Clinical Genetics Branch, and colleagues in Pediatric 

Blood and Cancer (2009;53:520–523).

DC is an inherited bone marrow failure syndrome (IBMFS) characterized by very high cancer risks 

and defects in telomere biology. The workshop was prompted by recent advances in understanding of the genetic defects present in DC and the success of NCI’s IBMFS study. The 80 participants 

included clinicians, scientists, patients with DC, their family members, and representatives from 

family support groups.

Clinicians and scientists studying DC discussed recent findings, created clinical care recommendations, and developed several new collaborative efforts designed to improve understanding of DC 

pathogenesis. The patients and family members, numbering 42 participants who represented 17 

families, attended a special session that gave them the tools needed to create a family support 

group. Information on the new group is available at www.dcoutreach.com. 

Dyskeratosis Congenita Workshop Report
March 2010 23

Risk varied inconsistently with glucose 

concentration. A stronger association 

between insulin level and prostate cancer 

risk was observed among leaner men and 

those who were less physically active at 

work. (Albanes D, Weinstein SJ, Wright ME, 

Männistö S, Limburg PJ, Snyder K, Virtamo J. 

Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. J Natl Cancer 

Inst 2009;101:1272–1279)

Meat and Related Compounds

The authors examined the associations 

between meat consumption (type, cooking method, and related mutagens), 

heme iron, nitrite/nitrate, and prostate 

cancer in a cohort of 175,343 U.S. men 

aged 50–71 years. During 9 years of 

follow-up, 10,313 prostate cancer cases 

(1,102 advanced) and 419 fatal cases 

were ascertained. HRs comparing 

the fifth intake quintile with the first 

revealed the following risks associated 

with red and processed meat for total 

Figure 3. Projected number of future cancers (mean and 95% uncertainty limits) that could be related to 

computed tomographic scan use in the United States in 2007, according to age at exposure. (Berrington de 

Gonzalez A, et al. 2009)

0

1,000

2,000

3,000

4,000

5,000

6,000

0–5 6–10 11–17 18–24 25–34 35–44 45–54 55–64 65–74 75–84 > 85

Age at exposure (years)

Projected number of future cancers

Females

Males

(red meat: HR = 1.12, processed meat: 

HR = 1.07, 95% confidence interval 

[CI] = 1.00–1.14) and advanced (red 

meat: HR = 1.31, processed meat: HR = 

1.32) prostate cancer. Heme iron, barbecued/grilled meat, and benzo[a]pyrene 

were all positively associated with total 

(HR = 1.09, 1.11, and 1.09, respectively) 

and advanced (HR = 1.28, 1.36, and 

1.28, respectively) disease. Nitrite 

(HR = 1.24) and nitrate (HR = 1.31) 

intakes were associated with advanced 

prostate cancer. No clear associations 

were found for fatal prostate cancer. Red 

and processed meat may be associated 

with prostate cancer via mechanisms 

involving heme iron, nitrite/nitrate, 

grilling/barbecuing, and benzo[a]

pyrene. (Sinha R, Park Y, Graubard BI, 

Leitzmann MF, Hollenbeck A, Schatzkin A, 

Cross AJ. Meat and meat-related compounds 

and risk of prostate cancer in a large prospective cohort study in the United States. Am J 

Epidemiol 2009;170:1165–1177)

Susceptibility Locus on 

Chromosome 8q24

 The authors reported on a GWAS in 

10,286 prostate cancer cases and 9,135 

controls of European ancestry in the 

Cancer Genetic Markers of Susceptibility 

(CGEMS) initiative. The investigators 

identified a new association with prostate cancer risk on chromosome 8q24 

(rs620861, p = 1.3 x 10–10, heterozygote 

OR = 1.17, homozygote OR = 1.33). This 

region is of special interest because it is 

located in a so-called “gene desert” and 

has been associated with several other 

forms of cancer. (Yeager M, Chatterjee N, 

Ciampa J, Jacobs KB, Gonzalez-Bosquet J, 

Hayes RB, Kraft P, Wacholder S, Orr N, Berndt 

S, Yu K, Hutchinson A, Wang Z, Amundadottir L, 

Feigelson HS, Thun MJ, Diver WR, Albanes 

D, Virtamo J, Weinstein S, Schumacher FR, 

Cancel-Tassin G, Cussenot O, Valeri A, Andriole 

GL, Crawford ED, Haiman CA, Henderson B, 

Kolonel L, Le Marchand L, Siddiq A, Riboli E, 

Key TJ, Kaaks R, Isaacs W, Isaacs S, Wiley KE, 

Gronberg H, Wiklund F, Stattin P, Xu J, Zheng 

SL, Sun J, Vatten LJ, Hveem K, Kumle M, Tucker 

M, Gerhard DS, Hoover RN, Fraumeni JF Jr, 

Hunter DJ, Thomas G, Chanock SJ. Identification of a new prostate cancer susceptibility locus on chromosome 8q24. Nat Genet

2009;41:1055–1057)

RADIATION

Projected Cancer Risks from Computed 

Tomographic Scans

The authors generated detailed estimates 

of future cancer risks from current computed tomographic (CT) scan use in the 

United States. Risk models based on the 

National Research Council’s “Biological 

Effects of Ionizing Radiation” report and 

organ-specific radiation doses derived 

from a national survey were used to estimate age-specific cancer risks for each 

scan type. Models were combined with 

age- and sex-specific scan frequencies 

for the United States in 2007 obtained 

from survey and insurance claims data. 

The authors estimated that about 29,000 
DCEG Linkage 24

future cancers could be related to CT 

scans performed in the United States in 

2007. The largest contributions, respectively, were from scans of the abdomen 

and pelvis, chest, and head and from 

chest CT angiography. One-third of the 

projected cancers were due to scans performed at ages 35–54 years, 15% were 

due to scans performed at ages younger 

than 18 years, and 66% were in females 

(see Figure 3). Estimates highlight several areas of CT scan use that make large 

contributions to the total cancer risk, 

including several scan types and age 

groups with a high frequency of use or 

scans involving relatively high doses, in 

which risk-reduction efforts may be 

warranted. (Berrington de Gonzalez A, Mahesh 

M, Kim KP, Bhargavan M, Lewis R, Mettler F, 

Land C. Projected cancer risks from CT scans 

performed in the U.S. in 2007. Arch Intern Med 

2009;169:2071–2077)

TESTICULAR CANCER

Organochlorine Exposures

Organochlorine (OC) compounds and 

the risk of testicular germ cell tumors 

(TGCTs) were studied in a nested casecontrol study of TGCTs within the 

Norwegian Janus Serum Bank cohort 

among individuals with serum collected 

between 1972 and 1978. TGCT cases 

diagnosed through 1999 (n = 49) 

were identified through linkage to the 

Norwegian Cancer Registry. Controls 

(n = 51) were matched to cases on region, 

blood draw year, and age at blood draw. 

TGCT cases had elevated concentrations of p,p'-DDE (tertile 3 vs. tertile 1 

OR [ORT3] = 2.2, pWilcoxon (W) = 0.07), 

oxychlordane (ORT3 = 3.2, pW = 0.05),

trans-nonachlor (ORT3 = 2.6, pW = 0.07), 

and total chlordanes (ORT3 = 2.0, pW = 

0.048) compared with controls, although 

no ORs were statistically significant. 

Seminoma cases had significantly lower 

concentrations of polychlorinated 

biphenyl (PCB) congeners 44, 49, and 

52 and significantly higher concentrations of PCBs 99, 138, 153, 167, 183, and 

Albanes D. Vitamin supplements and cancer prevention: Where do randomized controlled trials 

stand? J Natl Cancer Inst 2009;101:2–4

Anderson WF. Cancer surveillance research. Cancer Epidemiol Biomarkers Prev 2009;

18:1669–1671

Castle PE. Cervical cancers after HPV vaccination. Obstet Gynecol 2009;114:174

Castle PE. Should HPV vaccine be given to men? BMJ 2009;339:872–873

Castle PE. The evolving definition of carcinogenic HPV. Infect Agents Cancer 2009;7 (online)

Castle PE, et al. How to evaluate emerging technologies in cervical cancer screening? 

Int J Cancer 2009;125:2489–2496

Chang CM, et al. The extent of genetic diversity of Epstein-Barr virus and its geographic 

and disease patterns: A need for reappraisal. Virus Res 2009;143:209–221

Cook MB, et al. A systematic review and meta-analysis of perinatal variables in relation 

to the risk of testicular cancer. Int J Epidemiol 2009;38:1532–1542

Dawsey SM, et al. Environmental causes of esophageal cancer. Gastroenterol Clin N Am

2009;38:27–57

Giambartolomei C, et al. A mini-review of familial ovarian germ cell tumors: An additional 

manifestation of the familial testicular germ cell tumor syndrome. Cancer Epidemiol 2009;33:31–36

Gilbert ES. The impact of dosimetry uncertainties on dose-response analyses. Health Phys 

2009;97:487–492

Katki HA, et al. Risk estimation for the next generation of prevention programmes for cervical 

cancer. Lancet 2009;10:1022–1023

Linet MS, et al. Children’s exposure to diagnostic medical radiation and cancer risks: 

Epidemiologic and dosimetric considerations. Pediatr Radiol 2009;39:S4–S26

McGlynn KA, Cook MB. Etiologic factors in testicular germ-cell tumors. Future Oncol 

2009;5:1389–1402

Moore SC. Waist vs. weight—Which matters more for mortality? Am J Clin Nutr 2009;

89:1003–1004

O’Brien TR. Interferon-alfa, interferon-λ and hepatitis C. Nat Genet 2009;41:1048–1050

Pronk A, et al. Occupational exposure to diesel engine exhaust: A literature review. J Expos Sci 

Environ Epidemiol 2009;19:443–457

Savage SA. Dyskeratosis congenita. GENEReviews 2009 (online)

Schiffman M, Solomon D. Screening and prevention methods for cervical cancer. JAMA 

2009;302:1809–1810

Schiffman M, Wacholder S. From India to the world—A better way to prevent cervical cancer. 

N Engl J Med 2009;360:1453–1455

Schiffman M, et al. The use of HPV seroepidemiology to inform vaccine policy. Sex Transm Dis 

2009;36:675–679

Tucker MA. Melanoma epidemiology. Hematol Oncol Clin N Am 2009;23:383–395

Wentzensen N, et al. Utility of methylation markers in cervical cancer early detection: 

Appraisal of the state-of-the-science. Gynecol Oncol 2009;112:293–299

MAJOR EDITORIALS, COMMENTARIES, AND REVIEWS PUBLISHED BY DCEG SCIENTISTS
March 2010 25

Figure 4. Risk of (A) in situ and (B) invasive human papillomavirus (HPV)-associated cancers among persons 

with AIDS according to time relative to AIDS onset. Standardized incidence ratios (SIRs) and 95% confidence 

intervals (CIs) for in situ and invasive HPV-associated cancers are presented across the following five risk 

periods relative to AIDS onset: (a) 60–25 months before AIDS, (b) 24–7 months before AIDS, (c) 6 months 

before to 3 months after AIDS, (d) 4–27 months after AIDS, and (e) 28–60 months after AIDS. The AIDS onset 

period was excluded from trend analyses. (Chaturvedi AK, et al. 2009)

195. Results provide qualified evidence 

of an association between TGCT risk 

and exposures to p,p'-DDE, chlordane 

compounds, and possibly some PCB 

congeners. (Purdue MP, Engel LS, Langseth 

H, Needham LL, Andersen A, Barr DB, Blair A, 

Rothman N, McGlynn KA. Prediagnostic serum 

concentrations of organochlorine compounds 

and risk of testicular germ cell tumors. Environ 

Health Perspect 2009;117:1514–1519) 

VIRUSES

HPV-associated Cancers in Persons 

with AIDS

Investigators linked data on 499,230 

individuals diagnosed with AIDS from 

1980 through 2004 with cancer registries 

in 15 U.S. regions. Risk of in situ and 

invasive human papillomavirus (HPV)-

associated cancers, compared with that 

in the general population, was measured 

using standardized incidence ratios 

(SIRs). The relationship of immunosuppression with incidence 4–60 months 

after AIDS onset was evaluated by use 

of CD4 T-cell counts measured at AIDS 

onset. Incidence 4–60 months after 

AIDS onset was compared across three 

periods (1980–1989, 1990–1995, and 

1996–2004). Among persons with AIDS, 

the authors observed elevated risk of 

all HPV-associated in situ (SIRs ranged 

from 8.9 for cervical cancer to 68.6 for 

anal cancer among men) and invasive 

(SIRs ranged from 1.6 for oropharyngeal 

cancer to 34.6 for anal cancer among 

men) cancers (see Figure 4). During 

1996–2004, low CD4 T-cell count was 

associated with increased risk of invasive 

anal cancer among men (RR per decline 

of 100 CD4 T cells per cubic millimeter 

= 1.34) and possibly increased risk of in 

situ vaginal or vulvar cancer (RR = 1.52, 

CI = 0.99–2.35, p = 0.055) and invasive 

cervical cancer (RR = 1.32, CI = 0.96–

1.80, p = 0.077). Among men, incidence 

(per 100,000 person-years) of in situ and 

invasive anal cancer was higher during 

1996–2004 than during 1990–1995 (29.5 

a b c d e

1

3

10

30

100

a b c d e a b c d e a b c d e a b c d e

- -

- - - - -

- - -

- - -

-

-

- - - -

-

-

-

- - -

-

-

- - -

-

-

-

-

- - -

- -

-

-

-

-

- -

-

-

- - -

| |||

Anus (men) Anus (women) Cervix Penis Vagina or vulva

Months relative to AIDS onset

SIR (95% CI)

Ptrend< 0.001 Ptrend= 0.546 Ptrend< 0.001 Ptrend< 0.001 Ptrend< 0.001

a b c d e

1

3

10

30

100

a b c d e a b c d e a b c d e a b c d e a b c d e

-

-

-

- -

-

-

-

- -

- -

-

-

- - -

-

-

- -

- -

-

- -

-

-

-

-

-

- -

- - -

- -

-

-

-

- -

-

- -

-

-

-

- - -

-

-

- -

|||| |

Anus (men) Anus (women) Cervix Penis Vagina or vulva Oropharynx

SIR (95% CI)

Months relative to AIDS onset

Ptrend< 0.001 Ptrend< 0.001 Ptrend = 0.160 Ptrend= 0.004 Ptrend= 0.810

vs. 18.3 in situ cases, respectively, RR = 

1.71; 42.3 vs. 20.7 invasive cases, respectively, RR = 2.03). Incidence of other 

cancers was stable over time. (Chaturvedi 

AK, Madeleine MM, Biggar RJ, Engels EA. Risk 

of human papillomavirus-associated cancers 

among persons with AIDS. J Natl Cancer Inst 

2009;101:1120–1130)

A

B
DCEG Linkage 26

“Beta-carotene chemoprevention trials 

and lessons for cancer epidemiology and 

prevention” at the American Association 

for Cancer Research’s Frontiers in Cancer Prevention Research Conference in 

Houston, Texas.

In October, Amy Berrington de 

Gonzalez, D.Phil., Radiation Epidemiology Branch (REB), gave an invited 

talk on late health effects in irradiated 

populations at the Annual Meeting of 

the Radiation Research Society in 

Savannah, Georgia. 

DCEG PEOPLE IN THE NEWS

In September, Christian C. Abnet, 

Ph.D., M.P.H., Nutritional Epidemiology Branch (NEB), gave a keynote 

speech titled “Epidemiologic studies 

of esophageal cancer: Out of the lab 

and into people” at the University of 

Pittsburgh Department of Biological 

Science Annual Retreat in Pymatuning, 

Pennsylvania.

In December, Demetrius Albanes, 

M.D. (NEB), chaired a plenary session 

titled “Current controversies in nutritional epidemiology and cancer chemoprevention” and gave a presentation on 

In October, Louise A. Brinton, Ph.D.,

Chief of the Hormonal and Reproductive Epidemiology Branch (HREB), gave 

a presentation titled “Cancer risk among 

infertile women with androgen excess or 

menstrual disorders (including polycystic ovary syndrome)” at the American 

Society for Reproductive Medicine’s 65th 

Annual Meeting in Atlanta, Georgia.

In November, Neil E. Caporaso, M.D., 

Genetic Epidemiology Branch (GEB), 

and Dr. Stefan Ambs of the Center for 

Cancer Research co-led a session on 

health disparities and epidemiology 

during the Translational Research in 

Clinical Oncology Course on the NIH 

campus in Bethesda, Maryland.

In December, Carrie R. Daniel, Ph.D., 

M.P.H. (NEB), gave two talks—“Dietary 

patterns and scores for pooled analyses 

with body-size and mortality” and 

“Preliminary analysis and collaborative 

proposal to the Diet Working Group of 

the ACC”—at the Asian Cohort Consortium (ACC) meeting in Tokyo, Japan. 

In November, Sanford M. Dawsey, 

M.D. (NEB), gave invited talks on “PAH 

exposure—A universal risk factor for 

esophageal squamous cell carcinoma?” 

at the Cancer Council New South Wales 

in Sydney, Australia and on “Esophageal 

squamous cell carcinoma: The other 

esophageal cancer” at the Queensland 

Institute of Medical Research in Brisbane, Australia.

Eric A. Engels, M.D., M.P.H., Infections and Immunoepidemiology Branch 

(IIB), spoke in August on “Epidemiology of thymic malignancies” at the First 

International Conference on Thymic 

Malignancies at NIH in Bethesda, Maryland and in November on “Epidemiology 

Mark Schiffman Wins AACR-Prevent Cancer

Foundation Award

I

n December, Mark Schiffman, M.D., 

M.P.H., Clinical Genetics Branch, attended 

the 8th Annual International Conference on 

Frontiers in Cancer Prevention Research in 

Houston, Texas, where he received the American 

Association for Cancer Research (AACR)-Prevent 

Cancer Foundation Award for Excellence in 

Cancer Prevention Research and presented a 

lecture titled “Biomarkers and cancer prevention: 

Cautionary lessons from the study of human

 papillomavirus and cervical cancer.”

The AACR-Prevent Cancer Foundation Award for 

Excellence in Cancer Prevention Research is given 

annually to a scientist residing in any country in 

the world for his or her contributions to the field 

of cancer prevention. The scientist’s investigations must have been conducted in basic, translational, clinical, epidemiological, or behavioral science in cancer prevention research. Furthermore, 

these studies must have not only had a major impact on the field but also stimulated new directions 

in this important area.

Dr. Schiffman was chosen by peer review for his outstanding research on human papillomavirus 

infection and cervical carcinogenesis. The presenters noted that his work has changed cervical 

cancer screening and prevention in the United States and internationally. The award cites Dr. 

Schiffman’s research as a model of interdisciplinary science involving collaborations between 

molecular biologists, virologists, geneticists, vaccinologists, diagnosticians, clinicians, epidemiologists, and public health scientists and notes the combination of etiologic and preventive impact.

Mark Schiffman
March 2010 27

I

n October, Sam M. 

Mbulaiteye, M.D.,

Infections and Immunoepidemiology Branch, 

hosted five scientists from 

Uganda during a three-day 

visit to DCEG. The scientists met with members of 

DCEG, Information Management Services, Inc., 

and RTI International, Inc., 

to plan the fieldwork of a 

new collaborative study, 

East Africa Epidemiology 

of Burkitt Lymphoma in 

East African Children and 

Minors (EMBLEM). The 

Ugandan delegation promised to send the Division 

a Ugandan flag when the 

first child with Burkitt lymphoma is enrolled in the 

study, which is scheduled 

for early this year.

Ugandan Delegation Visits DCEG

Prevention Research in Houston, Texas 

and present her poster on “Alcohol 

consumption and TMPRSS2: ERG 

gene fusion in prostate cancer.”

In October, Thomas R. O’Brien, M.D., 

M.P.H. (IIB), spoke on “IL-28B predicts 

IFN response with hepatitis C” at the 

Perspectives in Melanoma XIII Meeting 

in Baltimore, Maryland.

In December, Preetha Rajaraman, 

Ph.D. (REB), gave an invited talk titled 

“Cancer risk after medical exposure: 

Second malignancies after childhood 

cancer in the Childhood Cancer Survivor Study (CCSS)” at the National 

Institute of Radiological Sciences in 

Chiba, Japan.

of cancer in HIV-infected people” at 

the American Society of Cytopathology 

Meeting in Denver, Colorado.

In October, Alisa M. Goldstein, Ph.D. 

(GEB), was the Scientific Program 

Chair for the 18th Annual Meeting of 

the International Genetic Epidemiology 

Society in Kahuku, Hawaii.

In November, Mark H. Greene, M.D., 

Chief of the Clinical Genetics Branch, 

presented “GOG-199 status report and 

a glimpse into the future of ovarian 

cancer screening” at the Society of 

Gynecologic Oncologists’ State of the 

Art Conference on Personalized Gynecologic Care in Washington, DC.

During a special session titled “Hematopoietic and lymphoid neoplasms” at 

the Surveillance, Epidemiology, and 

End Results (SEER) Principal Investigator Retreat, Ruth A. Kleinerman, 

M.P.H., and Lindsay M. Morton, 

Ph.D., both of REB, gave a joint invited 

talk on “Evolving classification of lymphoma: Relevance for epidemiologic 

research.” They spoke on the same topic 

at the Beebe Symposium in November 

in Washington, DC. During that same 

month, Ms. Kleinerman presented a 

poster on “Risk of second cancers following treatment for retinoblastoma 

since 1970” and Dr. Morton presented a 

poster on “Immunostaining for CD10, 

BCL6, MUM1, LMO2, and BCL2 to 

identify favorable survival for molecular 

subtypes of diffuse large B-cell lymphoma in a population-based study 

during the pre-rituximab era” at the 

NCI Translational Science Meeting in 

Vienna, Virginia.

In December, Shih-Wen (Wenny) 

Lin, Ph.D., M.P.H. (NEB), received a 

Scholar-in-Training Award to attend 

the American Association for Cancer 

Research meeting Frontiers in Cancer 

In October, Arthur Schatzkin, M.D., 

Dr.P.H., Chief of NEB, presented “A 

new partnership in biomedical and 

lifestyle research: The NIH-AARP 

Diet and Health Study” at the AARP 

Annual Meeting in Las Vegas, Nevada.

In September, Mark E. Sherman, M.D. 

(HREB), gave a lecture on “Etiologic 

heterogeneity in breast cancer: Pathway to prevention or road to ruin?” 

at Strangeways Research Laboratory 

at the University of Cambridge, United 

Kingdom. During the same month, 

Dr. Sherman and Gretchen L. Gierach, 

Ph.D. (HREB), gave a joint presentation titled “Mammographic density and 

breast cancer risk” at the Barbara Ann 

Karmanos Cancer Institute in Detroit, 

Michigan.

Ugandan Delegation at DCEG: (front) Joseph Fraumeni and Sam 

Mbulaiteye; (back) Patrick Kerchan, Allan Hildesheim, Mike Mbaziira, 

Tobias Kinyera, Olivia Namusisi, James Goedert, and Martin Ogwang.
DCEG Linkage 28

Meredith Shiels, Ph.D., and Edgar 

Simard, M.P.H., both of IIB, received 

Young Investigator Awards to attend the 

Conference on Retroviruses and Opportunistic Infections in San Francisco, 

California in February.

Rashmi Sinha, Ph.D. (NEB), gave talks 

on meat and meat-related carcinogens at 

the Harvard School of Public Health in 

Boston, Massachusetts; the University of 

Arkansas for Medical Sciences in Little 

Rock, Arkansas; and the National Cancer 

Center in Tokyo, Japan. She also spoke 

on “ASA24, a self-administered instrument for collecting 24-hour dietary recall 

information” and chaired a session on 

the Dietary Pattern Working Group at 

the Asian Cohort Consortium Meeting 

in Tokyo, Japan.

Rachael Stolzenberg-Solomon, 

Ph.D., M.P.H., R.D. (NEB), gave invited 

talks on pancreatic cancer in October 

at the Prevention Grand Rounds at 

Roswell Park Cancer Institute in Buffalo, 

New York; in November at the LunchLearnLink, Maryland Cigarette Restitution Fund Program, Johns Hopkins 

Bloomberg School of Public Health in 

Baltimore, Maryland; and in December 

at Imperial College London in the United 

Kingdom and as key speaker at a Pancreatic and Colorectal Cancer Minisymposium at the University Medical Center 

Utrecht in The Netherlands.

Philip R. Taylor, M.D., Sc.D. (GEB), 

spoke on “Micronutrients for the prevention of cancer: A success story” at the 

Office of Dietary Supplements Fall Seminar Series at NIH in Bethesda, Maryland 

in October and at the Cancer Council 

New South Wales Research Strategy and 

Scientific Development Unit in Sydney, 

Australia in November. He also presented 

“Upper gastrointestinal cancer genetic 

studies” at the InterSCOPE meeting at 

the Cancer Council New South Wales 

in Sydney, Australia in November and 

taught “Chemoprevention of cancer” 

at the Fundamentals of Oncology for 

Public Health Practitioners course at 

the Johns Hopkins Bloomberg School of 

Public Health in Baltimore, Maryland in 

December.

At the Society for Melanoma Research 

International Congress in Boston, 

Massachusetts in November, Margaret 

A. Tucker, M.D., Director of the Human 

Genetics Program and Chief of GEB, 

gave a talk on “UV melanoma risk” 

and Maria Teresa Landi, M.D., Ph.D.

(GEB), chaired the Melanoma Epidemiology Session and spoke on “Current 

knowledge and challenges in the epidemiology of melanoma.”

In January, Nicolas Wentzensen, 

M.D., Ph.D. (HREB), gave an invited 

presentation on “Screening test options: 

Current practice and future developments” at the Workshop for Cervical 

Cancer Prevention along the U.S.-Mexico 

Border in Albuquerque, New Mexico.

In December, Regina G. Ziegler, Ph.D., 

M.P.H., Epidemiology and Biostatistics 

Program, presented “A new approach to 

measuring steroid hormone exposure 

and metabolism in epidemiologic studies” at Harvard Medical School in 

Boston, Massachusetts.

Mercy Guech-Ongey, Ph.D., Infections 

and Immunoepidemiology Branch, and 

Gila Neta, Ph.D., Radiation Epidemiology Branch 

(REB), have been appointed to represent DCEG 

on the NIH Fellows Committee, also known 

as FelCom. They are replacing outgoing members 

Porcia Bradford, M.D., Genetic Epidemiology 

Branch, and Chu-Ling Yu, Sc.D. (REB). FelCom 

enhances communication among fellows and the 

NIH community and serves as a liaison to leaders 

of programs that affect the training experience. 

More information about FelCom is available at 

http://felcom.od.nih.gov. 

New FELCOM 

Representatives

I

n November, Julia Ciampa, M.Sc., Biostatistics Branch, won an 

NIH Graduate Student Research Award for her poster on “Derivation, 

evaluation, and application of a novel multilocus method for genomewide association studies: Implications for oncogenic potential of 8q24,” 

presented at the 10th NIH Graduate Student Research Symposium in 

Bethesda, Maryland. Winners receive a $1,000 travel award from the 

NIH Graduate Partnership Program office. Julia Ciampa

New FelCom Representatives: Mercy 

Guech-Ongey and Gila Neta.
March 2010 29

COMINGS . . . GOINGS

Amanda Black, 

Ph.D., M.P.H., joined 

the Epidemiology and 

Biostatistics Program 

as a staff scientist to 

work on the Prostate, 

Lung, Colorectal 

and Ovarian (PLCO) Cancer Screening Trial. She previously was a Cancer 

Prevention Fellow with the Early Detection Research Network in the Division 

of Cancer Prevention. She received a 

B.Sc. in biomedical science, an M.Sc. 

in medical laboratory science, a Ph.D. 

in epidemiology and public health from 

Queen’s University in Belfast, and an 

M.P.H. from the University of Manchester. Her research interests include 

early detection, screening, and disease 

etiology with particular focus on prostate and ovarian cancer.

David Capo-Ramos, 

M.D., M.P.H., joined 

the Genetic Epidemiology Branch as a 

research fellow. He 

received an M.D. in 

2007 and an M.P.H. 

in 2009 from the University of Puerto 

Rico. For his master’s dissertation, he 

examined the role of particulate matter 

emissions in asthma and other respiratory diseases among residents of two 

areas of Puerto Rico. Dr. Capo-Ramos 

is working with Maria Teresa Landi, 

M.D., Ph.D., on the etiology 

and progression of lung cancer.

Sharon ColesCalloway joined 

DCEG’s Administrative Resource 

Center (ARC) as 

the lead purchasing agent. She has 

worked as a purchasing agent at NCI for 

the past 10 years, providing procurement support to the Urologic Oncology 

Branch, Metabolism Branch, and Surgery Branch of the Center for Cancer 

Research. Ms. Coles-Calloway brings 

with her a wealth of experience and a 

can-do attitude. Before becoming a purchasing agent, she held administrative 

support positions with the U.S. Office 

of Personnel Management and the U.S. 

Department of Commerce.

Cher Dallal, Ph.D.,

joined the Hormonal 

and Reproductive 

Epidemiology Branch 

(HREB) as a Cancer 

Prevention Fellow. 

She has a B.A. in 

molecular and cell biology from the 

University of California, Berkeley; an 

M.P.H. from Yale University; an M.S.

 in applied biostatistics and epidemiology from the University of Southern 

California; and a Ph.D. in epidemiology 

from the University of Pittsburgh. In 

her doctoral dissertation, Dr. Dallal 

evaluated the relationship of estrogen 

metabolites to breast cancer risk. At 

DCEG, she is working with Louise A. 

Brinton, Ph.D., Chief of HREB, and 

Gretchen L. Gierach, Ph.D., to assess 

the relationships of hormones to endometrial and breast cancer risk in the 

Fracture Intervention Trial Follow-up 

Study and to evaluate physical activity as 

determined by accelerometer measurements in the Polish Breast Cancer Study. 

Sonja Dawsey

joined the Nutritional 

Epidemiology Branch 

(NEB) as a Cancer 

Research Training 

Award predoctoral 

fellow. She received a 

B.S. in cellular and molecular biology 

from the University of Michigan in Ann 

Arbor, Michigan. She is working with 

Christian C. Abnet, Ph.D., M.P.H.,

on esophageal cancer studies in Kenya.

Benjamin Emmanuel

joined the Infections 

and Immunoepidemiology Branch (IIB) as 

a special volunteer. 

He received a B.S. in 

biology from Wheaton 

College in Illinois and is completing 

an M.P.H. at George Washington University. He is working with Sam M. 

Mbulaiteye, M.D., on Burkitt lymphoma studies in Africa.

Sharon Coles-Calloway

Sonja Dawsey 

David Capo-Ramos

Benjamin Emmanuel

Cher Dallal

Amanda Black

Denise Stoneman started her career at NIH in 1978 as a secretary for the deputy director of the 

National Institute of Allergy and Infectious Diseases (NIAID). After spending 10 years at NIAID, 

she joined NCI as a grants technical assistant in the Division of Extramural Activities. She began 

working as a program assistant under Dr. Alan Rabson, NCI Deputy Director, in 1989 and was later 

promoted to administrative officer for MaryAnn Guerra, NCI’s Deputy Director for Management, in the 

Building 31 Administrative Resource Center (ARC). In 1998, Ms. Stoneman moved to the DCEG ARC, 

where she provided service to the Occupational and Environmental Epidemiology Branch, the Radiation Epidemiology Branch, and the Biostatistics Branch. She has been an invaluable asset to the ARC 

and the Division. Using her expertise and knowledge in the administrative and budget areas, she has 

trained many junior staff at the ARC, enabling them to obtain higher-level positions within NCI. After 

her retirement, Ms. Stoneman moved with her husband to a farm in North Carolina, where she plans 

to enjoy the great outdoors, running, hiking, riding horses, and kayaking.

Denise Stoneman Retires
DCEG Linkage 30

Betty Jane (B.J.) Stone, Ph.D., Biostatistics Branch (BB), retired in December after a 34-year career at DCEG. She joined the Division in 1975 as a 

part-time guest worker, offering her computer skills in exchange for on-the-job 

training in epidemiology. Six months later, she was hired full-time as a cancer 

expert, and she spent the remainder of her career in the Division.

Dr. Stone received a B.S. with honors from Swarthmore College and a Ph.D. from Stanford University, 

both in mathematics. Before joining NCI, she built mathematical models for research institutes and in 

private industry, and she also taught for two years at Harvey Mudd College. 

During her career at NCI, Dr. Stone provided statistical analysis and computer support to epidemiologists throughout the Division and coauthored several reports investigating geographic “hot spots” of 

cancer mortality identified from U.S. county-based maps. She was a scientific editor of monographs, 

research articles, and site visit reports—a role especially important to foreign-born scientists, many of 

whom benefited greatly from her superb editorial skills. Dr. Stone chaired the Technical Evaluation of 

Questionnaires Committee for more than 20 years and developed the Questionnaire Modules web site, 

a searchable collection of questionnaire modules that has proven useful to scientists who are developing questionnaires for new studies. She also served as an administrator of the NCI Cancer Genome 

Atlas web site.

Dr. Stone was a singer and orchestra manager for Washington, DC’s Friday Morning Music Club 

Chorale for two decades and was a member of the DCEG chorus. For many years, she recorded 

scientific texts for Recording for the Blind & Dyslexic. A regular blood donor at the NIH Blood Bank, 

she donated more than 15 gallons of blood over the years. Following her retirement, Dr. Stone moved 

to Carlsbad, California, where she plans to enjoy the weather and many activities. She will continue 

to provide scientific editing services to BB as a part-time contractor. 

B.J. Stone Retires

B.J. Stone

Jacqueline Feenster

joined the Office of 

Division Operations 

and Analysis (ODOA) 

as a scientific program specialist. She 

is working on data 

compilation and analysis for reporting 

and budget activities and is maintaining 

systems and databases used by DCEG 

and NIH. Previously, she was a protocol management specialist in the NIH 

Clinical Center’s Rehabilitation Medicine 

Department and the NCI Protocol and 

Information Office as well as a senior 

research coordinator for Johns Hopkins 

University. She received a B.S. from the 

University of Maryland, Eastern Shore.

Roberto Flores, Ph.D., M.P.H., joined 

IIB as a Cancer Prevention Fellow. He 

has a Ph.D. in nutritional sciences from 

the University of Arizona in Tucson 

and an M.P.H. from the Johns Hopkins 

Bloomberg School 

of Public Health. He 

previously worked as 

a laboratory scientist 

directing a human 

papillomavirus (HPV) 

molecular screening 

laboratory and developing and validating 

high-throughput real-time polymerase 

chain reaction assays for the absolute 

quantification of eight oncogenic HPV 

types. During his public health training, he evaluated national HPV vaccine 

implementation and cervical cancer 

screening programs in India. He is working with James J. Goedert, M.D., on 

research related to the association of the 

gut microbiome to cancer.

Jecholia Gallagher joined ODOA as a 

scientific program specialist. She received 

a B.A. from George Mason University in 

Fairfax, Virginia. She is working on data 

compilation and analysis for reporting 

and budget activities 

and is maintaining 

systems and databases 

used by DCEG and 

NIH. Previously, she 

worked at Global Solutions Network, Inc., 

and Ariel Research/3E Company, where 

she was the regulatory services coordinator and served on the integrative content 

team compiling and integrating chemical 

regulation information.

Choonsik Lee, Ph.D., 

joined the Radiation 

Epidemiology Branch 

(REB) as a tenuretrack investigator. He 

completed his Ph.D. 

in health physics at 

Hanyang University and postdoctoral 

fellowships in health physics and medical physics at the Innovative Technology 

Center for Radiation Safety in Korea and 

the University of Florida, respectively. 

His interests include human computational models, called hybrid phantoms. 

At REB, he is building the first comprehensive organ dose database for pediatric and adult patients from computed 

tomography and radiography examinations as well as analyzing organ doses 

from external radiation treatment using 

Monte Carlo simulation.

Shih-Wen (Wenny) 

Lin, Ph.D., M.P.H., 

joined NEB as a 

Cancer Prevention 

Fellow. She has a B.S. 

in biochemistry from 

the University of Delaware, a Ph.D. in cell and molecular biology from the University of Pennsylvania, 

and an M.P.H. from the Harvard School 

of Public Health. For her doctoral dissertation, she worked with Dr. Hildeg

HIV-1–specific adaptive immune 

responses elicited by prime-boost regimens using adenovirus and adenoassociated virus vectors as vaccine 

Roberto Flores

Wenny Lin

Jecholia Gallagher

Choonsik Lee

Jacqueline Feenster
March 2010 31

carriers. During her public health training, Dr. Lin explored the relationship of 

alcohol consumption to prostate cancer 

and of caffeine consumption to preterm 

birth. She is working with Christian C. 

Abnet, Ph.D., M.P.H., on the etiology of 

esophageal and stomach cancer.

Jacqueline Major, 

Ph.D., joined NEB as 

a postdoctoral fellow. 

She has an M.S. in statistics from San Diego 

State University and 

a Ph.D. in epidemiology from the University of California, 

San Diego (UCSD). For her doctoral dissertation, she worked with Dr. Hillary 

Klonoff-Cohen and Dr. Dan Mercola to 

examine body mass in relation to pathological, clinical, and genetic components 

of prostate cancer progression in men 

who underwent radical prostatectomy. 

She also worked with Dr. Elizabeth 

Barrett-Connor on the Rancho Bernardo 

Study to examine circulating insulin-like 

growth factor 1 (IGF-I) and subsequent 

cancer mortality. Before pursuing her 

doctorate, she was a senior statistician 

at UCSD Moores Cancer Center. Dr. 

Major is studying the etiology of prostate 

and other cancers, including the roles of 

growth factors, vitamins, trace elements, 

and genetic variants, with Demetrius 

Albanes, M.D. She is also working 

on novel statistical approaches to nutritional epidemiological analysis with 

Barry I. Graubard, Ph.D.; Arthur 

Schatzkin, M.D., Dr.P.H., Chief of 

NEB; and Rashmi Sinha, Ph.D.

Charles E. Matthews, Ph.D., has 

joined NEB as a physical activity epidemiologist. He received a B.S. in exercise 

science and a Ph.D. in epidemiology 

from the University of Massachusetts 

and an M.S. in exercise science from 

the University of South Carolina. He 

previously worked in the Department 

of Epidemiology and Biostatistics at the 

University of South Carolina and at the 

Vanderbilt University 

School of Medicine. 

His research program 

is designed to discover how to prevent 

and control cancer 

through etiologic and 

methodological studies of physical activity behaviors in the population.

Saloni Nayar joined the DCEG Office 

of Communications and Special Initiatives as an NCI Health Communications 

Intern. She will graduate with an M.P.H. 

from the University of Iowa this May. 

Sarah Nyante, Ph.D.,

joined HREB as a 

postdoctoral fellow. 

She received a B.S. in 

molecular, cellular, 

and developmental 

biology from Yale 

University and an M.S.P.H. and Ph.D. 

in epidemiology from the University of 

North Carolina at Chapel Hill. For her 

doctoral dissertation, she worked with 

Dr. Robert Millikan to assess the relationships between single nucleotide polymorphisms and basal-like and luminal A 

breast cancers in the Carolina Breast 

Cancer Study. She is focusing on the 

etiologic heterogeneity of breast and 

gynecologic cancers. 

Scott Quinlan, M.S., a predoctoral 

fellow with IIB, has left to take a position as a senior analyst at HealthCore in 

Wilmington, Delaware.

Elizabeth Hill Ruder, Ph.D., M.P.H., 

R.D., joined NEB as a Cancer Prevention 

Fellow. She has a B.S. in nutrition science from Cornell University, an M.P.H. 

from the Johns Hopkins Bloomberg 

School of Public Health, and a Ph.D. 

in nutrition science from Pennsylvania 

State University. A registered dietitian, 

she completed internship training at the 

Cleveland Clinic Foundation. For her 

doctoral dissertation, she worked with 

Dr. Terry Hartman 

of Penn State and 

Dr. Joanne Dorgan 

of Fox Chase Cancer 

Center to assess the 

relationship of birth 

characteristics to 

age at menarche and concentrations of 

serum sex hormones during adolescence. 

At NEB, she is working with Amanda 

J. Cross, Ph.D., and Rashmi Sinha, 

Ph.D., to assess diet-related risk factors 

for colorectal cancer.

David Wheeler, 

Ph.D., M.P.H., joined 

the Occupational and 

Environmental Epidemiology Branch as 

a Cancer Prevention 

Fellow. He holds an 

M.S. in applied statistics and a Ph.D. in 

geography, with a specialization in spatial statistics, from Ohio State University 

and an M.P.H. from Harvard University. 

His previous research includes applying statistical methods to investigate 

childhood cancer clusters and modeling 

ethnic disparities in disease with hierarchical Bayesian models. With his mentor, 

Mary H. Ward, Ph.D., he is working on 

multiple projects involving spatial analysis of cancer incidence and mortality 

data with a focus on lymphohematopoietic tumors in adults and children.

Jessica Wilcox was 

promoted to administrative officer in 

ARC. She is providing 

administrative and 

budget support to 

REB. Previously, she 

worked as an administrative technician 

in the ARC for three years, supporting 

the work of three senior administrative 

officers. She has many years of administrative experience and is committed to 

the mission of the ARC and DCEG.

Charles Matthews Elizabeth Ruder

Sarah Nyante

David Wheeler

Jacqueline Major

Jessica Wilcox
DCEG Linkage 32

NIH Publication No. 10-6051

Printed March 2010

Celebrating 30 Years of Cancer Research with China

I

n November, NCI and the Chinese 

Academy of Medical Sciences (CAMS) 

co-sponsored the workshop “Personalized cancer medicine: Building on thirty 

years of China-U.S. scientific progress,” 

which was held in Beijing to celebrate 

and foster collaborative cancer research. 

The meeting, chaired by Dr. Anna Barker, 

NCI Deputy Director, and Dr. Qimin 

Zhan, Vice President of CAMS, was 

attended by more than 100 scientists, 

including John Niederhuber, M.D., 

NCI Director. 

Several presentations by DCEG investigators, Division alumni, and long-time 

collaborators recognized and illustrated 

DCEG’s efforts in the long-standing 

collaborative research program. Ann W. 

Hsing, Ph.D., Hormonal and Reproductive Epidemiology Branch, discussed 

a multidisciplinary, population-based 

study conducted by DCEG and the 

Shanghai Cancer Institute (SCI) on 

biliary tract cancer, which is rising 

sharply in incidence in China. Qing 

Lan, M.D., Ph.D., M.P.H., Occupational and Environmental Epidemiology 

collaborations, including a case-control 

study of lung cancer in non-smoking 

women. Other presentations by U.S. and 

Chinese scientists focused on genomics, epigenomics, the next generation of 

sequencing, and their impact on cancer 

prevention and treatment. The meeting 

closed with a consensus that U.S.–China 

collaborations will become increasingly important in accelerating progress 

toward personalized cancer medicine on 

a global scale. n

—Ann W. Hsing, Ph.D. 

DCEG Presenters: Ann Hsing, Philip Taylor, and 

Qing Lan.

Branch, described collaborative work 

with the Chinese Center for Disease 

Control and Prevention that examined the relation of occupational 

benzene exposure to acute myeloid 

leukemia, aplastic anemia, and other 

hematopoietic disorders. Philip R. 

Taylor, M.D., Sc.D., Genetic Epidemiology Branch, reported on a 

clinical trial evaluating the effects of 

nutrient supplementation on esophageal cancer mortality in a high-risk 

population. 

Dr. Wei Zheng, professor and Chief 

of the Division of Epidemiology at 

Vanderbilt University, spoke on early 

results from the Shanghai Women’s 

Health Study. Dr. Wei-Cheng You, 

President of the Beijing Cancer Hospital at Peking University, described 

an intervention trial that tested the 

effect of anti-Helicobacter therapy 

and a COX-2 inhibitor on precursor 

lesions to gastric cancer. Both Drs. 

Zheng and You are DCEG alumni. 

Dr. Yu-Tang Gao, former Director of 

SCI, summarized several SCI–DCEG