bluuebunny/crossref_metadata_2025 huggingface dataset:
Explaining the Socioeconomic Variation in Cancer Risk in the Norwegian Women and Cancer Study
Authors: Braaten Tonje , Weiderpass Elisabete , Kumle Merethe , Lund Eiliv
Published: March 2006

Associations between level of education and cancer risk is well supported by scientific evidence, but previous studies could only partly adjust for relevant confounding factors. In this article, we examined how risk of cancer varies with level of education and identified factors that explain this variation using data from a prospective cohort study, including 93,638 Norwegian women who responded to an extensive questionnaire in 1991/1992 or 1996/1997. A total of 3,259 incident primary invasive cancer cases were diagnosed during follow-up, which ended in December 2001. We used Cox proportional hazards model to calculate relative risks (RR) with 95% confidence intervals (95% CI). Besides a similar overall risk of female cancers by level of education, we observed differing risks between educational groups for cancers of the lung, breast, cervix, kidney, and skin melanoma. Women with >16 years of education had an increased risk of breast cancer (RR, 1.46; 95% CI, 1.19-1.79) and a decreased risk of lung cancer (RR, 0.30; 95% CI, 0.13-0.70) and cervical cancer (RR, 0.38; 95% CI, 0.17-0.85) compared with the lowest educated women (7-9 years). The middle educated (13-16 years) had the lowest risk of kidney cancer (RR, 0.24; 95% CI, 0.08-0.71), whereas the risk of skin melanoma was highest among women with 10 to 12 years of education (RR, 1.53; 95% CI, 1.05-2.24) compared with the lowest educated women. After multivariate adjustment for potential confounders related to level of education, the variation in cancer risk according to educational levels declined into nonsignificance for all these sites.
Familial Aggregation and Heterogeneity of Non-Hodgkin Lymphoma in Population-Based Samples
Authors: Goldin Lynn R. , Landgren Ola , McMaster Mary L. , Gridley Gloria , Hemminki Kari , Li Xinjun , Mellemkjaer Lene , Olsen Jørgen H. , Linet Martha S.
Published: March 2006

The importance of genetic factors in the etiology of non-Hodgkin lymphoma (NHL) is suggested by case-control and cohort studies. Most previous studies have been too small to estimate accurately risks of specific categories of lymphoproliferative malignancies in relatives of NHL cases or to quantify the contribution of NHL case characteristics to familial risk. We have overcome sample size limitations and potential recall bias by using large databases from Sweden and Denmark. Diagnoses of lymphoproliferative malignancies were compared in 70,006 first-degree relatives of 26,089 NHL cases (including 7,432 with subtype information) versus 161,352 first-degree relatives of 58,960 matched controls. Relatives of NHL cases were at significantly increased risk for NHL [relative risk (RR), 1.73; 95% confidence interval (95% CI), 1.39-2.15], Hodgkin lymphoma (RR, 1.41; 95% CI, 1.0-1.97), and nonsignificantly for chronic lymphocytic leukemia (CLL; RR, 1.31; 95% CI, 0.93-1.85). No increased risk was found for multiple myeloma among case relatives. Findings with respect to siblings compared with parents and offspring or with respect to age at diagnosis of proband were inconsistent. In both populations, relatives of cases with an aggressive NHL subtype were at substantially increased risk of NHL (combined RR, 3.56; 95% CI, 1.80-7.02). We conclude that NHL has an important familial component, which is shared with Hodgkin lymphoma and CLL. We estimate that the absolute lifetime risk for a first-degree relative of an NHL case to develop NHL is 3.6% (compared with a population risk of 2.1%) and higher if the index case had an aggressive subtype of NHL.
Reduction in Breast Cancer Mortality from Organized Service Screening with Mammography: 1. Further Confirmation with Extended Data
Authors:   The Swedish Organised Service Screening Evaluation Group
Published: March 2006

Background: In an earlier publication, our evaluation of data from breast cancer screening programs in seven Swedish counties suggested a 40% reduction in incidence-based breast cancer mortality among women actually screened. In the current study, we expand the previous analysis from seven counties to 13 large areas within nine counties, including six of the original counties and seven additional areas, examine a longer period of follow-up (20-44 years), apply new analytic methods for the evaluation of incidence-based breast cancer mortality, and estimate the number needed to screen to save one life.

Methods: Data from six of the original counties (one being excluded as it does not yet have 10 years of follow-up after the initiation of screening), with increased follow-up, and seven additional large areas, within three counties, representing ∼45% of Swedish women, provide information about age at diagnosis, age at death, and screening history for 542,187 women in the prescreening and 566,423 women in the screening epochs. Regardless of year of diagnosis, there were a total of 6,231 deaths due to breast cancer in the period of study as a whole. Of these, 4,778 were incidence-based deaths in the two epochs, i.e., death among cases diagnosed within either the prescreening or screening period. Data were analyzed using Poisson regression and adjusted, when necessary, for self-selection bias, contemporaneous changes in incidence, and changes in mortality independent of screening.

Results: Attendance was uniformly high, averaging 75% in the screening epochs. Recall rates for assessment varied from 4% to 5% at the first round of screening and ∼3% at later rounds. Detection rates averaged five breast cancers per 1,000 women screened in the first round, and four breast cancers per 1,000 women screened in subsequent rounds. There was a significant 45% reduction in incidence-based breast cancer mortality among screened women in the screening epoch relative to incidence-based breast cancer mortality in the prescreening epoch (relative risk, 0.55; 95% confidence intervals, 0.51-0.59). After adjusting for self-selection bias, there still was a significant 43% reduction in incidence-based breast cancer mortality associated with screening (relative risk, 0.57; 95% confidence intervals, 0.53-0.62).

Conclusions: These results indicate a reduction in breast cancer mortality of between 40% and 45% in association with screening, after adjustment for self-selection bias. These results were obtained with modest human costs: the number needed to screen to save one life was estimated as 472. (Cancer Epidemiol Biomarkers Prev 2006;15(1):45–51)
γ-Radiation-Induced Chromosomal Mutagen Sensitivity Is Associated with Breast Cancer Risk in African-American Women: Caffeine Modulates the Outcome of Mutagen Sensitivity Assay
Authors: Natarajan Thanemozhi G. , Ganesan Natarajan , Carter-Nolan Pamela , Tucker Cynthia A. , Shields Peter G. , Adams-Campbell Lucile L.
Published: March 2006

Several different cancer studies have indicated that lymphocyte mutagen sensitivity is a marker of DNA repair deficiency and increased cancer risk. We have used a mutagen sensitivity assay (MSA) measuring γ-radiation-induced chromosomal aberrations in freshly cultured lymphocytes and assessed breast cancer risk in African-American women. Concurrently, we conducted duplicate cultures in the presence of caffeine, which overrides G2 arrest in cultured cells, decreases time to DNA repair, and hence increases the aberration rate. In comparison with the non–caffeine-treated cells, we are conceptually segregating the contribution of DNA repair and time for DNA repair as individual susceptibility phenotypes. Blood samples were obtained from 61 cases and 86 controls at Howard University Hospital. Two sets of whole-blood cultures were established and γ-irradiated (1 Gy) at 67 hours, one of which was treated with caffeine (1 mg/mL). Thereafter, cultures were processed for obtaining metaphase spreads. Fifty metaphases were screened for chromatid breaks. The mean breaks per cell (MBPC) for cases (0.34 ± 0.15) was significantly greater than for controls (0.24 ± 0.12; P < 0.0001). Using the 75th percentile value of controls as a cutoff to define mutagen sensitivity, the sensitive individuals had an odds ratio of 4.5 (95% confidence intervals, 2.2-9.1) for breast cancer compared with individuals that were not sensitive. The adjusted odds ratio was 3.3 (95% confidence intervals, 0.147-73.917), which was statistically significant but was limited by the small number of subjects. The results for caffeine co-culture were not predictive of breast cancer (MBPC: cases, 1.6 ± 0.9 versus controls, 1.5 ± 0.8; P = 0.8663). Comparing the MBPC for caffeine and noncaffeine cultures, there was a correlation in controls (n = 79; Spearman r = 0.4286; P < 0.0001), but not in cases (n = 58; Spearman r = 0.06609; P = 0.6221). This study indicates that the MSA phenotype is a risk factor for breast cancer in African-American women, with a significant effect observable even in small studies. The use of caffeine did not enhance the predictivity of MSA, but the correlation with non-caffeine cultures in controls indicates that the MSA phenotype is due to both DNA repair and G2 arrest capacity. (Cancer Epidemiol Biomarkers Prev 2006;15(3):437–42)
The Interaction of Four Genes in the Inflammation Pathway Significantly Predicts Prostate Cancer Risk
Authors: Xu Jianfeng , Lowey James , Wiklund Fredrik , Sun Jielin , Lindmark Fredrik , Hsu Fang-Chi , Dimitrov Latchezar , Chang Baoli , Turner Aubrey R. , Liu Wennan , Adami Hans-Olov , Suh Edward , Moore Jason H. , Zheng S. Lilly , Isaacs William B. , Trent Jeffrey M. , Grönberg Henrik
Published: March 2006

It is widely hypothesized that the interactions of multiple genes influence individual risk to prostate cancer. However, current efforts at identifying prostate cancer risk genes primarily rely on single-gene approaches. In an attempt to fill this gap, we carried out a study to explore the joint effect of multiple genes in the inflammation pathway on prostate cancer risk. We studied 20 genes in the Toll-like receptor signaling pathway as well as several cytokines. For each of these genes, we selected and genotyped haplotype-tagging single nucleotide polymorphisms (SNP) among 1,383 cases and 780 controls from the CAPS (CAncer Prostate in Sweden) study population. A total of 57 SNPs were included in the final analysis. A data mining method, multifactor dimensionality reduction, was used to explore the interaction effects of SNPs on prostate cancer risk. Interaction effects were assessed for all possible n SNP combinations, where n = 2, 3, or 4. For each n SNP combination, the model providing lowest prediction error among 100 cross-validations was chosen. The statistical significance levels of the best models in each n SNP combination were determined using permutation tests. A four-SNP interaction (one SNP each from IL-10, IL-1RN, TIRAP, and TLR5) had the lowest prediction error (43.28%, P = 0.019). Our ability to analyze a large number of SNPs in a large sample size is one of the first efforts in exploring the effect of high-order gene-gene interactions on prostate cancer risk, and this is an important contribution to this new and quickly evolving field.
Polymorphisms in the Estrogen Receptor α Gene and Mammographic Density
Authors: van Duijnhoven Fränzel J.B. , Bezemer Irene D. , Peeters Petra H.M. , Roest Mark , Uitterlinden André G. , Grobbee Diederick E. , van Gils Carla H.
Published: March 2006

The presence of the PvuII or the XbaI polymorphism in the estrogen receptor α gene (ESR1, 6q25) has been related to breast cancer risk; however, results are not fully consistent. To further elucidate this relation, we examined these polymorphisms in relation with mammographic density, a measure of dense tissue in the breast, which is strongly associated with breast cancer risk. For this study, 620 participants aged 49 to 68 years were selected from the Prospect-European Prospective Investigation into Cancer and Nutrition cohort. Blood samples, lifestyle– and medical questionnaire data and mammograms were available for these women. Genotyping was done using the TaqMan PCR assay and mammographic density was assessed using a computer-assisted method. Means of mammographic density were compared by ESR1 genotypes and haplotypes. The percentage density was higher in women with one or two copies of the PvuII p allele (means for Pp and pp are 37% and 36%, respectively) than in those with the PP genotype (32%, Ptrend = 0.09). Women with one or two copies of the XbaI x allele had higher mean percentage density (Xx and xx, 36% and 37%, respectively) than those with the XX genotype (31%, Ptrend < 0.01). Haplotype 1 (px) was associated with increased density, whereas haplotype 2 (PX) was associated with decreased density, both suggesting an allele-dose effect (Ptrend = 0.08 and <0.01, respectively). Similar associations were found with absolute density (Ptrend < 0.01). The findings of this study support the view that ESR1 polymorphisms may affect breast cancer risk through differences in breast density.
Family History Assessment to Detect Increased Risk for Colorectal Cancer: Conceptual Considerations and a Preliminary Economic Analysis
Authors: Ramsey Scott D. , Burke Wylie , Pinsky Linda , Clarke Lauren , Newcomb Polly , Khoury Muin J.
Published: March 2006

Background: Although the rationale for earlier screening of persons with a family history of colorectal cancer is plausible, there is no direct evidence that earlier assessment is either effective or cost-effective.

Objective: To estimate the clinical and economic effect of using family history assessment to identify persons for colorectal cancer screening before age 50.

Methods: We developed a decision model to compare costs and outcomes for two scenarios: (a) standard population screening starting at age 50; (b) family history assessment at age 40, followed by screening colonoscopy at age 40 for those with a suggestive family history of colorectal cancer. The analysis was conducted using the health insurer perspective.

Results: Using U.S. population estimates, 22 million would be eligible for family history assessment, and one million would be eligible for early colonoscopy; 2,834 invasive cancers would be detected, and 29,331 life years would be gained. The initial program cost would be $900 million. The discounted cost per life year gained of family history assessment versus no assessment equals $58,228. The results were most sensitive to the life expectancy benefit from earlier screening, the cost of colonoscopy, and the relative risk of colon cancer in those with a family history.

Conclusions: The cost-effectiveness of family history assessment for colorectal cancer approaches that of other widely accepted technologies; yet, the results are sensitive to several assumptions where better data are needed. Because of the relatively high prevalence of family history in the population, careful analysis and empirical data are needed.
Methyl-CpG Binding Domain 1Gene Polymorphisms and Risk of Primary Lung Cancer
Authors: Jang Jin-Sung , Lee Su Jeong , Choi Jin Eun , Cha Sung Ick , Lee Eung Bae , Park Tae In , Kim Chang Ho , Lee Won Kee , Kam Sin , Choi Je-Yong , Kang Young Mo , Park Rang-Woon , Kim In-San , Cho Young Lae , Jung Tae Hoon , Han Sung Beom , Park Jae Yong
Published: March 2006

The methyl-CpG binding domain 1 (MBD1) protein plays an important role for transcriptional regulation of gene expression. Polymorphisms and haplotypes of the MBD1 gene may have an influence on MBD1 activity on gene expression profiles, thereby modulating an individual's susceptibility to lung cancer. To test this hypothesis, we investigated the association of MBD1 −634G>A, −501delT (−501 T/T, T/−, −/−), and Pro401Ala genotypes and their haplotypes with the risk of lung cancer in a Korean population. The MBD1 genotype was determined in 432 lung cancer patients and in 432 healthy control subjects who were frequency matched for age and gender. The −634GG genotype was associated with a significantly increased risk of overall lung cancer compared with the −634AA genotype [adjusted odds ratio (OR), 3.10; 95% confidence interval (95% CI), 1.24-7.75; P = 0.016]. When analyses were stratified according to the tumor histology, the −634GG genotype was associated with a significantly increased risk of adenocarcinoma compared with the −634AA genotype (adjusted OR, 4.72; 95% CI, 1.61-13.82; P = 0.005). For the MBD1 −501delT and Pro401Ala polymorphisms, the −501 T/T genotype was associated with a marginal significantly increased risk of adenocarcinoma compared with the −501−/− genotype (adjusted OR, 2.07; 95% CI, 1.02-4.20; P = 0.045), and the Pro/Pro genotype was associated with a significantly increased risk of adenocarcinoma compared with the Ala/Ala genotype (adjusted OR, 3.41; 95% CI, 1.21-9.60; P = 0.02). Consistent with the genotyping analyses, the −634G/−501T/401Pro haplotype was associated with a significantly increased risk of overall lung cancer and adenocarcinoma compared with the −634A/−501−/401Ala haplotype (adjusted OR, 1.44; 95% CI, 1.08-1.91; P = 0.012 and Pc = 0.048; adjusted OR, 1.75; 95% CI, 1.20-2.56; P = 0.004 and Pc = 0.016, respectively). On a promoter assay, the −634A allele had significantly higher promoter activity compared with the −634G allele in the Chinese hamster ovary cells and A549 cells (P < 0.05 and P < 0.001, respectively), but the −501delT polymorphism did not have an effect on the promoter activity. When comparing the promoter activity of the MBD1 haplotypes, the −634A/−501− haplotype had a significantly higher promoter activity than the −634G/−501T haplotype (P < 0.001). These results suggest that the MBD1 −634G>A, −501delT, and Pro401Ala polymorphisms and their haplotypes contribute to the genetic susceptibility for lung cancer and particularly for adenocarcinoma.
Intentions to Participate in Genetics Research among African American Smokers
Authors: Halbert Chanita Hughes , Gandy Oscar H. , Collier Aliya , Shaker Lee
Published: March 2006

Although prior studies have shown that African American smokers are likely to carry some of the genetic variants associated with smoking risk, additional research with African American smokers is needed to replicate these findings. Limited information is available on interest in participating in research to identify genetic risk factors for smoking among African American smokers; therefore, the goals of the present study were to describe intentions to participate in smoking and genetics research, and to determine factors that are associated with participation intentions. Subjects were 128 African American male and female adult smokers. Sociodemographic characteristics, clinical factors, attitudes about genetic testing, and intentions to participate in genetics research were evaluated during a structured telephone interview. Overall, 58% of respondents reported that they would be very likely to participate in research to identify genetic risk factors for smoking. Greater beliefs about the benefits of participating in medical research (odds ratio, 3.17; 95% confidence interval, 1.45-6.94; P = 0.004) and fewer perceptions of the limitations and risks of genetic testing (odds ratio, 0.90; 95% confidence interval, 0.82-0.98; P = 0.01) had significant independent associations with reporting a high likelihood of participating in this type of research. Recruitment messages and protocols that address the benefits of research participation, as well as concerns about the limitations and risks of genetic testing, may enhance African American participation in research on genetics and smoking. (Cancer Epidemiol Biomarkers Prev 2006;(15)1:150–3)
A Multilevel Study of Socioeconomic Predictors of Regular Mammography Use Among African-American Women
Authors: Rosenberg Lynn , Wise Lauren A. , Palmer Julie R. , Horton Nicholas J. , Adams-Campbell Lucile L.
Published: March 2006

Background: Little is known about the predictors of adherence to mammography guidelines by African-American women. We assessed individual-level and group-level socioeconomic predictors of regular mammography use in a large cohort of African-American women.

Methods: We included 14,706 participants in the Black Women's Health Study who were 40 to 69 years of age at baseline in 1995. Data were obtained through mail questionnaires at entry and biennially during three 2-year follow-up periods until 2001. We linked the women's addresses to census block (neighborhood) socioeconomic data. With multilevel multivariable regression analysis, we assessed the relation of individual-level and neighborhood socioeconomic factors to “regular” mammography use (use in all three follow-up periods) relative to nonregular use, with control for other predictors.

Results: Most participants had health insurance and almost half had graduated college. Having health insurance was the socioeconomic variable most strongly associated with regular mammography use (odds ratio, 3.59; 95% confidence interval 3.02-4.28); the association was present at all levels of educational attainment, household income, and neighborhood socioeconomic status. Regular mammography use increased with individual household income: odds ratio, 2.00 (95% confidence interval, 1.58-2.53) for household income >$100,000 relative to <$15,001. Regular mammography use did not vary across level of education. Higher neighborhood socioeconomic status was significantly associated with regular mammography use before, but not after, control for household income.

Conclusions: Access to health insurance is strongly associated with regular mammography use among African-American women, even at higher levels of educational attainment and socioeconomic status. Neighborhood socioeconomic characteristics do not materially influence regular use.
p53 Mutation Analysis in Breast Tumors by a DNA Microarray Method
Authors: Tennis Meredith , Krishnan Shiva , Bonner Matthew , Ambrosone Christine B. , Vena John E. , Moysich Kirsten , Swede Helen , McCann Susan , Hall Per , Shields Peter G. , Freudenheim Jo L.
Published: March 2006

The p53 gene acts as a regulator of cell growth and DNA repair in normal cells; inactivation of the gene seems to lead to cancer. It is the most commonly mutated gene in human cancers, and a high-throughput sequencing method is needed for cancer etiology studies using large sample sets. In our population-based case-control study of breast cancer, the p53 gene was amplified by PCR for 392 subjects from seven hospitals in Western New York using the Affymetrix GeneChip technology. One hundred thirty-eight (35%) of the breast tumors had p53 mutations, of which 88% were located in exons 5 to 8. New hotspots were identified at codons 179, 195, 196, 213, 217, 249, 254, 278, 281, and 298, and previously reported hotspots were found at codons 175, 248, and 273. Manual sequencing for exons 5 to 9 of the p53 gene was done for 139 tumors to validate the Affymetrix assay. The two methods had 100% concordance for mutations detectable by the Affymetrix assay. We also successfully assayed paraffin-embedded breast and lung tumors from as early as 1958 and employed a nested PCR strategy to improve weak PCR amplification. To have statistical power, the investigation of gene environment interactions and cancer requires a large number of tumor analyses, which are frequently only available from archived tissue from multiple sources. We have shown the utility of the Affymetrix GeneChip method under these challenging conditions and provided new data for the mutational spectra of breast cancer in a population-based study. (Cancer Epidemiol Biomarkers Prev 2006;15(1):80–5)
Anal Human Papillomavirus Infection in Women and Its Relationship with Cervical Infection
Authors: Hernandez Brenda Y. , McDuffie Katharine , Zhu Xuemei , Wilkens Lynne R. , Killeen Jeffrey , Kessel Bruce , Wakabayashi Mark T. , Bertram Cathy C. , Easa David , Ning Lily , Boyd Jamie , Sunoo Christian , Kamemoto Lori , Goodman Marc T.
Published: March 2006

Human papillomavirus (HPV), the primary cause of cervical cancer, is also associated with the development of anal cancer. Relatively little is known about the epidemiology of anal HPV infection among healthy females and its relationship to cervical infection. We sought to characterize anal HPV infection in a cohort of adult women in Hawaii. Overall, 27% (372 of 1,378) of women were positive for anal HPV DNA at baseline compared with 29% (692 of 2,372) with cervical HPV DNA. Among women with paired anal and cervical samples, anal infection without accompanying cervical infection was observed in 14% (190 of 1,363). Concurrent anal and cervical HPV infections were observed in 13% (178 of 1,363) of women. Women with cervical HPV infection had >3-fold increased risk of concurrent anal infection. Concurrent anal and cervical HPV infection was most prevalent among the youngest women and steadily decreased through age 50 years. By contrast, the prevalence of anal infection alone remained relatively steady in all age groups. Compared with cervical infections, the overall distribution of HPV genotypes in the anus was more heterogeneous and included a greater proportion of nononcogenic types. A high degree of genotype-specific concordance was observed among concurrent anal and cervical infections, indicating a common source of infection. Nevertheless, the association of anal intercourse with anal HPV infection was limited to those women without accompanying cervical infection. The relationship of anal to cervical infection as described in this study has implications for the development of anal malignancies in women.
Coexpression of β1,6-N-Acetylglucosaminyltransferase V Glycoprotein Substrates Defines Aggressive Breast Cancers with Poor Outcome
Authors: Siddiqui Summar F. , Pawelek John , Handerson Tamara , Lin Chen-Yong , Dickson Robert B. , Rimm David L. , Camp Robert L.
Published: March 2006

β1,6-N-Acetylglucosaminyltransferase-V (GnT-V) catalyzes the addition of complex oligosaccharide side chains to glycoproteins, regulating the expression and function of several proteins involved in tumor metastasis. We analyzed the expression of five cell-surface glycoprotein substrates of GnT-V, matriptase, β1-integrin, epidermal growth factor receptor, lamp-1, and N-cadherin, on a tissue microarray cohort of 670 breast carcinomas with 30-year follow-up. Phaseolus vulgaris leukocytic phytohemagglutinin (LPHA), a lectin specific for β1,6-branched oligosaccharides, was used to assay GnT-V activity. Our results show a high degree of correlation of the LPHA staining with matriptase, lamp-1, and N-cadherin expressions, but not with epidermal growth factor receptor or β1-integrin expressions. In addition, many of the GnT-V substrate proteins exhibited strong coassociations. Elevated levels of GnT-V substrates were correlated with various markers of tumor progression, including positive node status, large tumor size, estrogen receptor negativity, HER2/neu overexpression, and high nuclear grade. Furthermore, LPHA and matriptase showed significant association with disease-related survival. Unsupervised hierarchical clustering of the GnT-V substrate protein expression and LPHA revealed two distinct clusters: one with higher expression of all markers and poor patient outcome and one with lower expression and good outcome. These clusters showed independent prognostic value for disease-related survival when compared with traditional markers of tumor progression. Our results indicate that GnT-V substrate proteins represent a unique subset of coexpressed tumor markers associated with aggressive disease.
Levels of C-Peptide and Mammographic Breast Density
Authors: Diorio Caroline , Pollak Michael , Byrne Celia , Mâsse Benoît , Hébert-Croteau Nicole , Yaffe Martin , Coté Gary , Bérubé Sylvie , Brisson Jacques
Published: March 2006

Members of the insulin-like growth factor family have been associated with breast cancer risk and mammographic breast density, one of the strongest known breast cancer risk indicators. The aim of this cross-sectional study was to examine the association of levels of C-peptide (a marker of insulin secretion) with mammographic breast density among 1,499 healthy women recruited during screening mammography examinations. At time of mammography, blood samples and time since last meal were collected. Plasma C-peptide levels were measured by ELISA method, and mammographic breast density by a computer-assisted method. Spearman's partial correlation coefficients, adjusting for age and time since last meal (when necessary), were used to evaluate the associations. High body mass index and waist-to-hip ratio measurements were independently correlated with high levels of C-peptide (rs = 0.173 and rs = 0.252, respectively; P < 0.0001) or low breast density (rs = −0.389 and rs = −0.142, respectively; P < 0.0001). High levels of C-peptide were correlated with low breast density (rs = −0.210, P < 0.0001). However, the strength of the negative correlation was substantially reduced and was no longer significant after further adjustment for body mass index and waist-to-hip ratio (rs = −0.022, P = 0.41). These results suggest that C-peptide levels are not associated with breast density after complete adjustment for adiposity. Thus, the insulin/C-peptide–breast density relation does not seem to mirror the insulin/C-peptide–breast cancer association.
Migration History, Acculturation, and Breast Cancer Risk in Hispanic Women
Authors: John Esther M. , Phipps Amanda I. , Davis Adam , Koo Jocelyn
Published: March 2006

Background: Migrant studies have shown that breast cancer risk increases in women who move from countries with low incidence rates to countries with high rates. We examined the influence of migration history and acculturation on breast cancer risk in Hispanic women ages 35 to 79 years.

Methods: In a population-based case-control study conducted in the San Francisco Bay Area, information on migration history, language usage, and other risk factors for breast cancer was collected through an in-person interview for 991 cases and 1,285 controls.

Results: Breast cancer risk was 50% lower in foreign-born Hispanics than U.S.-born Hispanics. Risk increased with increasing duration of residence in the United States, decreasing age at migration, and increasing acculturation. Among long-term foreign-born residents, risk was lower among Hispanics who moved to the United States at age ≥20 years and those who spoke mostly Spanish. The difference in risk between third-generation or higher-generation Hispanics and recent migrants from rural areas was ∼6-fold in postmenopausal women and 4-fold in premenopausal women. Adjustment for differences in the distribution of breast cancer risk factors greatly attenuated the associations with migration patterns in premenopausal women; reduced risks remained only in those who resided in the United States for <10 years or migrated at age ≥30 years. In postmenopausal women, a 25% to 30% lower risk remained among long-term residents and those who migrated to the United States before age 20 years.

Conclusions: These findings suggest the importance of yet unidentified protective factors among both recent premenopausal migrants and postmenopausal migrants. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2905–13)
Joint Effects of the CYP1A1 MspI, ERα PvuII, and ERα XbaI Polymorphisms on the Risk of Breast Cancer: Results from a Population-Based Case-Control Study in Shanghai, China
Authors: Shen Yueping , Li De-Kun , Wu Junqing , Zhang Zibao , Gao Ersheng
Published: March 2006

Estrogen-metabolizing gene and estrogen receptor (ER) genes are the possible risk factors implicated in the initiation and development of breast through estrogen tumorigenesis pathway. We examined whether CYP1A1 MspI, ERα PvuII, and ERα XbaI genetic polymorphisms could increase the risk of breast cancer among Chinese women and gene-gene joint effect on the breast cancer risk in a subset from a population-based case-control study conducted in urban Shanghai from January 1, 1998 and November 31, 2001. PCR-RFLP method based on buccal cells was used to examine the three candidate polymorphisms in 282 breast cancer cases and 298 controls. Compared with CYP1A1 MspI m1/m1, the risk of breast cancer was doubled for genotypes CYP1A1 MspI m1/m2 [odds ratio (OR), 1.83; 95% confidence interval (95% CI), 1.24-2.69] and CYP1A1 MspI m2/m2 (OR, 2.22; 95% CI, 1.26-3.85). The association seemed to be stronger among cases diagnosed older than 45 years and women without a family history of breast cancer. ERα PvuII pp and ERα XbaI xx polymorphisms, which are in possible linkage disequilibrium, were both associated with a nonsignificantly elevated risk in all subjects; the associations seemed to be stronger among women with a family history of breast cancer. There seems to be a joint effect on the breast cancer risk between CYP1A1 MspI and ERα XbaI genotypes (m2/m2 and xx; OR, 5.87; 95% CI, 1.38-24.98), between CYP1A1 MspI and ERα PvuII genotypes (m2/m2 and pp; OR, 2.39; 95% CI, 0.81-7.07), and among all three genotypes (m2/m2, pp, and xx; OR, 8.07; 95% CI, 1.45-44.77). Results of this study indicate that estrogen-metabolizing genes and estrogen receptor may jointly play a role in the etiology of breast cancer. (Cencer Epidemiol Biomarkers Prev2006;15(2):342–7)
No Evidence of False Reassurance among Women with an Inconclusive BRCA1/2 Genetic Test Result
Authors: Dorval Michel , Gauthier Geneviève , Maunsell Elizabeth , Dugas Michel J. , Rouleau Isabelle , Chiquette Jocelyne , Plante Marie , Laframboise Rachel , Gaudet Michel , Bridge Peter J. ,   INHERIT BRCAs, Simard Jacques
Published: March 2006

Background: Little is known about how women who receive an inconclusive result from BRCA1/2 testing interpret their result. Clinical observations suggest that some of them may be falsely reassured and, consequently, may not adhere to recommended surveillance. The purpose of this study is to evaluate whether women with inconclusive BRCA1/2 test results are falsely reassured.

Methods: Participants were adult women with a family history suggestive of a germ-line mutation in either the BRCA1 or the BRCA2 gene who underwent genetic testing in the context of the interdisciplinary research program INHERIT BRCAs. Data were collected using selfadministered questionnaires at genetic counseling and 1 month after result disclosure. Reassurance was assessed through indicators of cancer risk perception, cancer worry, relief following result disclosure, painfulness of the test result, and its effect on quality of life.

Results: Five-hundred women (105 carriers, 140 noncarriers, and 255 inconclusive) were included in this analysis. Compared to noncarriers, women with inconclusive results had higher cancer risk perception, were more worried about cancer, were less relieved by their test result, and perceived their quality of life as being more adversely affected by it.

Conclusion: The differences observed between noncarriers and women who received an inconclusive result run counter to the hypothesis that the latter are falsely reassured following BRCA1/2 testing. For clinicians, our findings show the value of taking precautions to fully explain to women that inconclusive results do not rule out the possibility that they still may face a higher risk of developing breast and/or ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2862–7)
Effect of Acid Suppression on Molecular Predictors for Esophageal Cancer
Authors: Lao-Sirieix Pierre , Roy Amanda , Worrall Claire , Vowler Sarah L. , Gardiner Sue , Fitzgerald Rebecca C.
Published: March 2006

Background: Gastroesophageal reflux disease is a risk factor for the development of Barrett's esophagus and esophageal adenocarcinoma. The effect of antireflux therapy on the incidence of esophageal adenocarcinoma is unknown. Acid exposure in vitro induces hyperproliferation via a cyclooxygenase-2 (COX-2) dependent mechanism. Epidemiologic and animal studies suggest that COX inhibitors decrease the incidence of esophageal adenocarcinoma.

Aim: To study the differential effect of complete compared with incomplete acid suppression on proliferation, apoptosis, and COX-2.

Patients and Methods: Fifty-one patients with Barrett's esophagus who underwent pH monitoring were divided into two groups according to their DeMeester score: 32 acid-suppressed patients (group 1) and 19 patients with abnormally high acid exposure (group 2). Slides from biopsies taken 3 months before and 4 and 12 months after pH monitoring were stained for Mcm2, COX-2, c-myc, and cleaved caspase-3 (marker of apoptosis).

Results: There was no evidence of a difference between the two groups in terms of age, gender ratio, medication, dysplasia status, and the expression levels of any marker before pH monitoring. In group 1, Mcm2 expression decreased in the luminal surface and throughout the tissue 12 months after monitoring when compared with the two previous time points (P < 0.05). The levels of COX-2 increased overtime (P < 0.01 in group 1, not significant in group 2). There was no correlation between Mcm2 and COX-2 expression. Acid suppression had no effect on c-myc or apoptosis.

Conclusion: Long-term acid suppression reduces proliferation in Barrett's esophagus samples but has no advantageous effect on c-myc, apoptosis, or COX-2. (Cancer Epidemiol Biomarkers Prev 2006;15(2):288–93)
Folate, Vitamin B6, and Vitamin B12 Intake and the Risk of Breast Cancer Among Mexican Women
Authors: Lajous Martin , Lazcano-Ponce Eduardo , Hernandez-Avila Mauricio , Willett Walter , Romieu Isabelle
Published: March 2006

Background: High intake of folate, vitamin B6, and vitamin B12 have been hypothesized to lower the risk for breast cancer. We conducted a population-based case-control study to evaluate the risk for breast cancer among Mexican women with relatively low vitamin intakes.

Methods: We included 475 women (median age, 53 years; range, 23-87 years) diagnosed with incident breast cancer through six hospitals in Mexico City and interviewed them to obtain data on breast cancer risk factors and their usual diet using a food frequency questionnaire. We selected 1,391 (median age, 49 years; range, 18-82 years) controls from the Mexico City population using a national sampling frame.

Results: Compared with women in the lowest quartile, the odds ratio for breast cancer for women in the highest quartile of folate intake was 0.64 [95% confidence intervals (CI), 0.45-0.90; P, test for trend = 0.009] and 0.32 (95% CI, 0.22-0.49; P, test for trend < 0.0001) for vitamin B12 intake. Among postmenopausal women, intakes of folate and vitamin B12 were associated with a lower risk of breast cancer and those associations were stronger than among premenopausal women. The inverse association of folate and breast cancer was stronger among women who consumed a high level of vitamin B12 as compared with women consuming diets low in vitamin B12. No association was observed for vitamin B6 intake.

Conclusions: In this population, high intakes of folate and vitamin B12 were independently associated with decreased breast cancer risk, particularly among postmenopausal women. (Cancer Epidemiol Biomarkers Prev 2006;15(3):443–8)
AIB1 Polymorphisms Predict Aggressive Ovarian Cancer Phenotype
Authors: Li Andrew J. , Lerner Dimitry L. , Gapuzan Maria-Emily R. , Karlan Beth Y.
Published: March 2006

Purpose: The androgen receptor (AR) harbors a polymorphic CAG repeat sequence in exon 1, coding for a polyglutamine tract whose length inversely correlates with AR transactivation function. AIB1, an AR coactivator, expresses a similar polymorphic glutamine sequence within the carboxyl-terminal coding region. We hypothesized that genotypic variations in the androgen-signaling pathway promote aggressive epithelial ovarian cancer biology, and sought to examine the effect of AIB1 genotype on clinical outcome.

Experimental Design: Genotype analysis of the AIB1 CAG repeat region was done on 89 patients with epithelial ovarian cancer. Medical records were reviewed for clinicopathologic factors and survival. Data were examined using the χ2 test and Kaplan-Meier survival and Cox regression analyses.

Results: We identified four AIB1 genotypes, with glutamine codon lengths of 26, 28, 29, and 30. Patients with a short AIB1 genotype (with ≤28 CAG repeats) showed statistically shorter time to disease recurrence compared to those with a long genotype (≥29 CAG repeats; 15.0 versus 30.0 months; P = 0.01). Patients with short AIB1 also showed decreased overall survival (57.0 months) compared to those with a long genotype (median survival not yet reached; P = 0.02). When controlling for established prognostic factors, multivariate analysis identified the presence of a short AIB1 genotype as an independent poor prognostic factor for overall survival (P = 0.05).

Conclusions: These data suggest that short AIB1 genotypes may promote aggressive malignant phenotypes of epithelial ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2919–22)
Family History of Hemolymphopoietic and Other Cancers and Risk of Non-Hodgkin's Lymphoma
Authors: Negri Eva , Talamini Renato , Montella Maurizio , Dal Maso Luigino , Crispo Anna , Spina Michele , La Vecchia Carlo , Franceschi Silvia
Published: March 2006

We investigated the risk of lymphomas, hemolymphopoietic (HLP) cancers (including lymphomas), and non-HLP cancers in first-degree relatives of non-Hodgkin's lymphoma (NHL) cases in an Italian case-control study on 225 patients (median age, 59 years) with a new diagnosis of NHL and 504 hospital controls (median age, 63 years), admitted for a wide spectrum of acute, nonneoplastic, nonimmune conditions. We estimated odds ratios (OR) adjusted for sex, age, family size, and other potential confounders. We also built the cohort of all first-degree relatives and computed age and sex adjusted hazard ratios (HR) using proportional hazard models. A history of lymphoma in first-degree relatives was reported by 5 NHL cases and 3 controls [OR, 3.2; 95% confidence interval (95% CI), 0.7-14.4] whereas 14 cases and 11 controls reported a family history of HLP cancers (OR, 3.0; 95% CI, 1.2-7.0). The HR of relatives of NHL cases, compared with relatives of controls, was 4.5 (95% CI, 1.1-18.8) for lymphomas, 3.5 (95% CI, 1.5-7.4) for HLP cancers, 1.6 (95% CI, 1.3-2.0) for all cancers, and 1.0 (95% CI, 0.9-1.1) for all causes of deaths. The HRs were higher for relatives of NHL cases diagnosed before the age of 50 years: 7.1 for HLP cancers, 2.0 for all cancers, and 1.6 for all deaths. A family history of cancer of the liver (OR, 2.1; 95% CI, 1.0-4.2), breast (OR, 2.0; 95% CI, 1.0-3.6), and kidney (OR, 4.6; 95% CI, 1.0-20.9) increased NHL risk. The OR was also elevated for all cancer sites (OR, 1.7 95% CI, 1.2-2.4) and the risk increased with the number of affected relatives also when HLP cancers were excluded. (Cancer Epidemiol Biomarkers Prev 2006;15(2):245–50)
Residential Insecticide Use and Risk of Non-Hodgkin's Lymphoma
Authors: Colt Joanne S. , Davis Scott , Severson Richard K. , Lynch Charles F. , Cozen Wendy , Camann David , Engels Eric A. , Blair Aaron , Hartge Patricia
Published: March 2006

Previous studies have linked non-Hodgkin's lymphoma (NHL) with occupational exposure to insecticides, but residential use is largely unexplored. In this population-based case-control study, we examined NHL risk and use of insecticides in the home and garden. We identified NHL cases, uninfected with HIV, diagnosed between 1998 and 2000 among women and men ages 20 to 74 years in Iowa and the metropolitan areas of Los Angeles, Detroit, and Seattle. Controls were selected using random digit dialing or Medicare files. Computer-assisted personal interviews (1,321 cases and 1,057 controls) elicited data on insecticide use at each home occupied since 1970. Insecticide levels were measured in dust taken from used vacuum cleaner bags (682 cases and 513 controls). We previously reported a positive association with dichlorodiphenyldichloroethylene levels in carpet dust residues. Here, we focus on insecticides that were commonly used after 1970, the time period covered by our questionnaire. People whose homes were treated for termites had elevated NHL risk (odds ratio, 1.3; 95% confidence interval, 1.0-1.6). Risk was modestly, although not significantly, elevated in all but one study center and in all sexes and races. The elevation in risk was restricted to people whose homes were treated before the 1988 chlordane ban. There was a significant trend of increasing risk with increasing levels of α-chlordane residues in dust (Ptrend = 0.04) and a marginally significant trend for γ-chlordane (Ptrend = 0.06). We found no evidence of associations for insects overall, for specific types of insects other than termites, or for elevated residues of other insecticides. We concluded that chlordane treatment of homes for termites may increase residents' NHL risk. (Cancer Epidemiol Biomarkers Prev 2006;15(2):251–7)
A Prospective Study of Lycopene and Tomato Product Intake and Risk of Prostate Cancer
Authors: Kirsh Victoria A. , Mayne Susan T. , Peters Ulrike , Chatterjee Nilanjan , Leitzmann Michael F. , Dixon L. Beth , Urban Donald A. , Crawford E. David , Hayes Richard B.
Published: March 2006

Background: Dietary lycopene and tomato products may reduce risk of prostate cancer; however, uncertainty remains about this possible association.

Methods: We evaluated the association between intake of lycopene and specific tomato products and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to investigate cancer early detection methods and etiologic determinants. Participants completed both a general risk factor and a 137-item food frequency questionnaire at baseline. A total of 1,338 cases of prostate cancer were identified among 29,361 men during an average of 4.2 years of follow-up.

Results: Lycopene intake was not associated with prostate cancer risk. Reduced risks were also not found for total tomato servings or for most tomato-based foods. Statistically nonsignificant inverse associations were noted for pizza [all prostate cancer: relative risk (RR), 0.83; 95% confidence interval (95% CI), 0.67-1.03 for ≥1 serving/wk versus < 0.5 serving/mo; Ptrend = 0.06 and advanced prostate cancer: RR, 0.79; 95% CI, 0.56-1.10; Ptrend = 0.12] and spaghetti/tomato sauce consumption (advanced prostate cancer: RR = 0.81, 95% CI, 0.57-1.16 for ≥2 servings/wk versus < 1 serving/mo; Ptrend = 0.31). Among men with a family history of prostate cancer, risks were decreased in relation to increased consumption of lycopene (Ptrend = 0.04) and specific tomato-based foods commonly eaten with fat (spaghetti, Ptrend = 0.12; pizza, Ptrend = 0.15; lasagna, Ptrend = 0.02).

Conclusions: This large study does not support the hypothesis that greater lycopene/tomato product consumption protects from prostate cancer. Evidence for protective associations in subjects with a family history of prostate cancer requires further corroboration. (Cancer Epidemiol Biomarkers Prev 2006;15(1):92–8)