bluuebunny/crossref_metadata_2025 huggingface dataset:
The CHEK2*1100delC Allelic Variant and Risk of Breast Cancer: Screening Results from the Breast Cancer Family Registry
Authors: Bernstein Jonine L. , Teraoka Sharon N. , John Esther M. , Andrulis Irene L. , Knight Julia A. , Lapinski Robert , Olson Eric R. , Wolitzer Abigail L. , Seminara Daniela , Whittemore Alice S. , Concannon Patrick
Published: March 2006

CHEK2, a serine-threonine kinase, is activated in response to agents, such as ionizing radiation, which induce DNA double-strand breaks. Activation of CHEK2 can result in cell cycle checkpoint arrest or apoptosis. One specific variant, CHEK2*1100delC, has been associated with an increased risk of breast cancer. In this population-based study, we screened 2,311 female breast cancer cases and 496 general population controls enrolled in the Ontario and Northern California Breast Cancer Family Registries for this variant (all controls were Canadian). Overall, 30 cases and one control carried the 1100delC allele. In Ontario, the weighted mutation carrier frequency among cases and controls was 1.34% and 0.20%, respectively [odds ratio (OR), 6.65; 95% confidence interval (95% CI), 2.37-18.68]. In California, the weighted population mutation carrier frequency in cases was 0.40%. Across all cases, 1 of 524 non-Caucasians (0.19%) and 29 of 1,775 Caucasians (1.63%) were mutation carriers (OR, 0.12; 95% CI, 0.02-0.89). Among Caucasian cases >45 years age at diagnosis, carrier status was associated with history of benign breast disease (OR, 3.18; 95% CI, 1.30-7.80) and exposure to diagnostic ionizing radiation (excluding mammography; OR, 3.21; 95% CI, 1.13-9.14); compared with women without exposure to ionizing radiation, the association was strongest among women exposed >15 years before diagnosis (OR, 4.28; 95% CI, 1.50-12.20) and among those who received two or more chest X-rays (OR, 3.63; 95% CI, 1.25-10.52). These data supporting the biological relevance of CHEK2 in breast carcinogenesis suggest that further studies examining the joint roles of CHEK2*1100delC carrier status and radiation exposure may be warranted.(Cancer Epidemiol Biomarkers Prev 2006;15(2):348–52)
Endogenous Sex Hormone Levels and Mammographic Density among Postmenopausal Women
Authors: Tamimi Rulla M. , Hankinson Susan E. , Colditz Graham A. , Byrne Celia
Published: March 2006

Background: Mammographic density is one of the strongest predictors of breast cancer risk. The mechanism by which breast density increases breast cancer risk is unclear although it has been hypothesized that breast density reflects cumulative exposure to estrogens.

Methods: To evaluate this hypothesis, we conducted a cross-sectional study among 520 postmenopausal women in the Nurses' Health Study that examined the relation between circulating sex hormones and mammographic density. Women were postmenopausal and not taking exogenous hormones at the time of blood collection and mammogram. Percent breast density was measured from digitized mammograms using a computer-assisted method. Circulating estrone, estradiol, androstenedione, testosterone, DHEA, DHEA sulfate, sex hormone–binding globulin, progesterone, and prolactin were measured in plasma.

Results: In contrast to the prior hypothesis, circulating estrogens were inversely related to percent mammographic density. The mean percent mammographic density was 25.6% among women in the lowest quartile of circulating estradiol compared with 14.4% among women in the highest quartile [Spearman correlation (r) = −0.22, P < 0.0001]. Circulating estrogens alone explained 1% to 5% of the variation of mammographic density. Body mass index was positively associated with circulating estradiol levels (r = 0.45, P < 0.0001) and inversely related to percent mammographic density (r = −0.51, P < 0.0001). After adjustment for body mass index, there was no association between estradiol and breast density (r = 0.01, P = 0.81). Likewise, there was no relation between the other sex hormones measured or prolactin and mammographic density after adjustment for body mass index.

Conclusion: These findings indicate that in postmenopausal women, mammographic density is independent of circulating sex hormone levels.
Physical Activity in Relation to Mammographic Density in the Dutch Prospect-European Prospective Investigation into Cancer and Nutrition Cohort
Authors: Suijkerbuijk Karijn P.M. , Van Duijnhoven Fränzel J.B. , Van Gils Carla H. , Van Noord Paulus A.H. , Peeters Petra H.M. , Friedenreich Christine M. , Monninkhof Evelyn M.
Published: March 2006

Background: Evidence accumulates that physical inactivity is one of the few modifiable risk factors for breast cancer. The mechanism through which physical inactivity affects breast cancer risk is not clear. The study aim was to investigate the association between physical activity and breast density because mammographic density is strongly associated with breast cancer risk.

Methods: We did a cross-sectional study in 620 women, of ages 49 to 68 years and participants of the Dutch Prospect-European Prospective Investigation into Cancer and Nutrition cohort. A self-administered questionnaire was used to obtain information on duration and intensity of physical activity (recreational, household, and occupational) during the year preceding study recruitment. A total activity index (inactive, moderately inactive, moderately active, and active) was estimated by combining all activity types. Percent and absolute breast density were determined on screening mammograms using a computer-aided method. Multivariate linear regression was used to examine the association between physical activity and breast density.

Results: Mean percent density was 35.3% [95% confidence interval (95% CI), 31.8-38.8] for the inactive category compared with 36.1% (95% CI, 33.0-39.2) for the active category. Mean absolute density values for the inactive and active category were 45.8 cm2 (95% CI, 40.9-50.7) and 42.6 cm2 (95% CI, 38.3-47.0), respectively. Subgroup analysis for postmenopausal women showed similar results, as did separate analyses for recreational and household activity.

Conclusions: The result does not support a relation between current physical activity and mammographic density in postmenopausal women. (Cancer Epidemiol Biomarkers Prev 2006;15(3):456–60)
Sexual Behavior, Condom Use, and Human Papillomavirus: Pooled Analysis of the IARC Human Papillomavirus Prevalence Surveys
Authors: Vaccarella Salvatore , Franceschi Silvia , Herrero Rolando , Muñoz Nubia , Snijders Peter J.F. , Clifford Gary M. , Smith Jennifer S. , Lazcano-Ponce Eduardo , Sukvirach Sukhon , Shin Hai-Rim , de Sanjosé Silvia , Molano Monica , Matos Elena , Ferreccio Catterina , Thi Hoang Anh Pham , Thomas Jaiye O. , Meijer Chris J.L.M. ,   IARC HPV Prevalence Surveys Study Group
Published: March 2006

Human papillomavirus (HPV) is a sexually transmitted infection but it is unclear whether differences in transmission efficacy exist between individual HPV types. Information on sexual behavior was collected from 11 areas in four continents among population-based, age-stratified random samples of women of ages ≥15 years. HPV testing was done using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate odds ratios (OR) of being HPV positive and corresponding 95% confidence intervals (95% CI). Variables were analyzed categorically. When more than two groups were compared, floating confidence intervals were estimated by treating ORs as floating absolute risks. A total of 11,337 women (mean age, 41.9 years) were available. We confirmed that lifetime number of sexual partners is associated with HPV positivity (OR for ≥2 versus 1, 1.86; 95% CI, 1.63-2.11) but the association was not a linear one for HPV18, 31, and 33 (i.e., no clear increase for ≥3 versus 2 sexual partners). Women who had multiple-type infection and high-risk HPV type infection reported a statistically nonsignificant higher number of sexual partners than women who had single-type and low-risk type infections, respectively. Early age at sexual debut was not significantly related to HPV positivity. Husband's extramarital sexual relationships were associated with an OR of 1.45 (95% CI, 1.24-1.70) for HPV positivity in their wives after adjustment for age and lifetime number of women's sexual partners. We did not observe a significant association with condom use. Our study showed an effect of both women's and their husbands' sexual behavior on HPV positivity. Furthermore, it suggests some differences in the pattern of the association between sexual behavior and different HPV types.(Cancer Epidemiol Biomarkers Prev 2006;15(2):326–33)
Variation in DNA Repair GenesERCC2, XRCC1, andXRCC3and Risk of Follicular Lymphoma
Authors: Ekström Smedby Karin , Lindgren Cecilia M. , Hjalgrim Henrik , Humphreys Keith , Schöllkopf Claudia , Chang Ellen T. , Roos Göran , Ryder Lars P. , Falk Kerstin I. , Palmgren Juni , Kere Juha , Melbye Mads , Glimelius Bengt , Adami Hans-Olov
Published: March 2006

The reasons for the positive association between skin cancer and non-Hodgkin's lymphoma are not known but may be due to common susceptibility involving suboptimal DNA repair. Therefore, we investigated selected polymorphisms and haplotypes in three DNA repair genes, previously associated with skin cancer and DNA repair capacity, in risk of follicular lymphoma, including possible gene interaction with cigarette smoking and sun exposure. We genotyped 19 single nucleotide polymorphisms (SNP) in the ERCC2, XRCC1, and XRCC3 genes in 430 follicular lymphoma patients and 605 controls within a population-based case-control study in Denmark and Sweden. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression and haplotype associations were assessed with a global score test. We observed no associations between variation in the ERCC2 and XRCC1 genes and follicular lymphoma risk. In XRCC3, increased risk of follicular lymphoma was suggested for rare homozygotes of three SNPs [Rs3212024: OR, 1.8 (95% CI, 1.1-2.8); Rs3212038: OR, 1.5 (95% CI, 1.0-2.4); Rs3212090: OR, 1.5 (95% CI, 1.0-2.5)]. These results were strengthened in current cigarette smokers. However, evidence of differences in XRCC3 haplotype distributions between follicular lymphoma cases and controls was weak, both overall and in current smokers. We conclude that polymorphic variation in the XRCC3 gene, but not in ERCC2 or XRCC1, may be of importance for susceptibility to follicular lymphoma, perhaps primarily in current smokers. The link between skin cancer and follicular lymphoma is unlikely to be mediated through common variation in the studied DNA repair gene polymorphisms. (Cancer Epidemiol Biomarkers Prev 2006;15(2)–65)
APC I1307K and the Risk of Prostate Cancer
Authors: Poynter Jenny N. , Cooney Kathleen A. , Bonner Joseph D. , White Kirsten A. , Tomsho Lynn P. , Rennert Gad , Gruber Stephen B.
Published: March 2006

The kin-cohort design has been proposed as an alternative to traditional case-control and cohort measures to evaluate inherited susceptibility to cancer in population-based studies. Here, we used this design to evaluate inherited susceptibility to prostate cancer associated with APC I1307K using data from the Molecular Epidemiology of Colorectal Cancer study. Two techniques were used to compare the incidence of prostate cancer in APC I1307K carriers. First, we compared the incidence of prostate cancer in relatives of mutation carriers and noncarriers using standard techniques for survival analysis. Second, we used the marginal maximum likelihood method for kin-cohort analysis to infer the genotypes in the relatives. We also evaluated APC I1307K in 75 Ashkenazi Jewish individuals with prostate cancer from 27 families enrolled in the University of Michigan Prostate Cancer Genetic Study. We observed a slightly increased risk of prostate cancer in relatives of APC I1307K carriers, however, this difference was not statistically significant (hazard ratio, 1.6; 95% confidence intervals, 0.7-3.4). Similar conclusions were drawn using both techniques for kin-cohort analysis. APC I1307K was found in 7.4% of families genotyped, which is slightly higher than the allele prevalence reported in Ashkenazi Jews in the general population. In addition, we did not observe loss of heterozygosity at APC or a somatic mutation near APC I1307K using microdissected tumor DNA from mutation carriers enrolled in the Prostate Cancer Genetic Study. Overall, the evidence for an association between APC I1307K and prostate cancer is not compelling. APC I1307K is unlikely to play a clinically meaningful role in susceptibility to prostate cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(3):468–73)
A Prospective Study of Calcium Intake and Incident and Fatal Prostate Cancer
Authors: Giovannucci Edward , Liu Yan , Stampfer Meir J. , Willett Walter C.
Published: March 2006

Prostate cancer is the most common incident cancer and the second leading cause of cancer mortality in U.S. males. Higher milk intake has been relatively consistently associated with an increased risk of prostate cancer, especially advanced prostate cancer. Some data suggest that high intake of calcium might account for this association, but this relationship remains controversial. We hypothesized that high calcium intake, possibly by lowering 1,25(OH)2 vitamin D levels, is associated with poorer differentiation in prostate cancer and thereby with fatal prostate cancer. We examined calcium intake in relation to prostate cancer risk using data from the Health Professionals Follow-up Study, a prospective cohort study of 47,750 male health professionals with no history of cancer other than nonmelanoma skin cancer at baseline. We assessed total, dietary, and supplementary calcium intake in 1986, 1990, 1994, and 1998, using a validated food frequency questionnaire. We calculated the multivariable relative risk (RR) and 95% confidence intervals (95% CI) using Cox proportional hazards regression. Over 16 years of follow-up, we identified 3,544 total cases of prostate cancer, 523 advanced (extraprostatic) cases, and 312 fatal cases. Higher calcium intake was not appreciably associated with total or nonadvanced prostate cancer but was associated with a higher risk of advanced and fatal prostate cancer [for fatal prostate cancer, compared with men whose long-term calcium intake was 500-749 mg/d (excluding supplement use of <5 years); those with intakes of 1,500-1,999 mg/d had a RR, 1.87; 95% CI, 1.17-3.01; and those with ≥2,000 mg/d had a RR, 2.43; 95% CI, 1.32-4.48; Ptrend = 0.003]. Dietary calcium and supplementary calcium were independently associated with an increased risk. For high-grade prostate cancer (Gleason ≥ 7), an association was observed for high versus low calcium intake (RR, 1.89; 95% CI, 1.32-2.71; Ptrend = 0.005), but a nonsignificant, inverse association was observed for organ-confined, low-grade prostate cancer (RR, 0.79; 95% CI, 0.50-1.25; Ptrend = 0.09). In a sample of this cohort, higher calcium intake was associated with lower circulating 1,25(OH)2 vitamin D levels. Our findings suggest that calcium intakes exceeding 1,500 mg/d may be associated with a decrease in differentiation in prostate cancer and ultimately with a higher risk of advanced and fatal prostate cancer but not with well-differentiated, organ-confined cancers. (Cancer Epidemiol Biomarkers Prev 2006;15(2):203–10)
Data-Dredging Gene-Dose Analyses in Association Studies: Biases and their Corrections
Authors: Lee Wen-Chung , Huang Hsiao-Yuan
Published: March 2006

To examine the joint effect of multiple loci on disease risk, many case-control association studies used “gene-dose analyses.” However, some researchers defined high-risk genotypes (or alleles) as those that have higher genotypic (allelic) frequencies in the case group compared with the control group in the study. This will lead to the total number of the “high-risk” genotypes (alleles) tending to be higher for the cases than for the controls as well, even if none of the studied loci were related to the disease. Monte-Carlo simulations done in this study showed that such a “data-dredging” gene-dose analysis could produce grossly biased results. A permutation correction method was proposed which could correct the biases very effectively. (Cancer Epidemiol Biomarkers Prev 2005;14(12):3004–6)
Dairy, Calcium, and Vitamin D Intake and Postmenopausal Breast Cancer Risk in the Cancer Prevention Study II Nutrition Cohort
Authors: McCullough Marjorie L. , Rodriguez Carmen , Diver W. Ryan , Feigelson Heather Spencer , Stevens Victoria L. , Thun Michael J. , Calle Eugenia E.
Published: March 2006

Background: Calcium, vitamin D, and dairy products are highly correlated factors, each with potential roles in breast carcinogenesis. Few prospective studies have examined these relationships in postmenopausal women.

Methods: Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed questionnaire on diet, vitamin and mineral supplement use, medical history, and lifestyle in 1992 to 1993. After exclusion of women with a history of cancer and incomplete dietary data, 68,567 postmenopausal women remained for analysis. During follow-up through August 31, 2001, we identified 2,855 incident cases of breast cancer. Multivariate-adjusted rate ratios (RR) were calculated using Cox proportional hazards models.

Results: Women with the highest intake of dietary calcium (>1,250 mg/d) were at a lower risk of breast cancer than those reporting ≤500 mg/d [RR, 0.80; 95% confidence interval (95% CI), 0.67-0.95; Ptrend = 0.02]; however, neither use of supplemental calcium nor vitamin D intake was associated with risk. Consumption starting at two or more servings of dairy products per day was likewise inversely associated with risk (RR, 0.81; 95% CI, 0.69-0.95; Ptrend = 0.002, compared with <0.5 servings/d). The associations were slightly stronger in women with estrogen receptor–positive tumors comparing highest to lowest intake: dietary calcium (RR, 0.67; 95% CI, 0.51-0.88; Ptrend = 0.004); dairy products (RR, 0.73; 95% CI, 0.57-0.93; Ptrend = 0.0003), and dietary vitamin D (RR, 0.74; 95% CI, 0.59-0.93; Ptrend = 0.006).

Conclusions: Our results support the hypothesis that dietary calcium and/or some other components in dairy products may modestly reduce risk of postmenopausal breast cancer. The stronger inverse associations among estrogen receptor–positive tumors deserve further study. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2898–904)
Effect of NAT1 and NAT2 Genetic Polymorphisms on Colorectal Cancer Risk Associated with Exposure to Tobacco Smoke and Meat Consumption
Authors: Lilla Carmen , Verla-Tebit Emaculate , Risch Angela , Jäger Birgit , Hoffmeister Michael , Brenner Hermann , Chang-Claude Jenny
Published: March 2006

N-Acetyltransferases 1 and 2 (NAT1 and NAT2), both being highly polymorphic, are involved in the metabolism of aromatic and heterocyclic aromatic amines present in cigarette smoke and red meat cooked by high-temperature cooking techniques. We investigated the effect of differences in acetylation capacity, determined by NAT1 and NAT2 genotypes, on colorectal cancer risk associated with exposure to tobacco smoke or red meat consumption. In this population-based case-control study in Germany, 505 patients with incident colorectal cancer and 604 age- and sex-matched control individuals with genotyping data and detailed risk factor information were included. Genotyping of NAT1 and NAT2 genetic polymorphisms was done using a fluorescence-based melting curve analysis method. The association between genotypes, environmental exposures, and colorectal cancer risk was estimated using multivariate logistic regression. Colorectal cancer risk associated with active smoking was elevated after accumulation of 30+ pack-years of smoking [odds ratio (OR), 1.4; 95% confidence interval (95% CI), 0.9-2.2] but not significantly modified by either NAT1 or NAT2 genotype. Exposure to environmental tobacco smoke was associated with an increased risk for colorectal cancer only among NAT2 fast acetylators (OR, 2.6; 95% CI, 1.1-5.9 for exposure in childhood and adulthood). Frequent consumption of red meat significantly increased colorectal cancer risk for the group comprising all NAT2 fast acetylators or carriers of the NAT1*10 allele (OR, 2.6; 95% CI, 1.1-6.1) but not among those with “slow” NAT1 and NAT2 genotypes. Our findings indicate that NAT1 and NAT2 genotypes may contribute jointly to individual susceptibility and that heterocyclic aromatic amines may play an important role in colorectal cancer associated with red meat and possibly also exposure to environmental tobacco smoke. (Cancer Epidemiol Biomarkers Prev 2006;15(1):99–107)
Plasma C-Reactive Protein and Risk of Cancer: A Prospective Study from Greece
Authors: Trichopoulos Dimitrios , Psaltopoulou Theodora , Orfanos Philippos , Trichopoulou Antonia , Boffetta Paolo
Published: March 2006

Background: Inflammation is an important component of carcinogenesis but little research has been conducted on whether inflammation markers can be predictive of cancer risk in humans.

Methods: We analyzed C-reactive protein (CRP), a marker of inflammation, in plasma samples of 496 cases of cancer and 996 controls selected among participants in a prospective study from Greece.

Results: Plasma CRP level was higher in cancer cases than controls (odds ratio for increase in CRP level of 3.2 mg/L, 1.20; 95% confidence interval, 1.10-1.32): The corresponding odds ratio after exclusion of the first year of follow-up and of individuals with CRP level above 20 mg/L was 1.32 (95% confidence interval, 1.15-1.52). Although based on small number of cases, the association between elevated plasma CRP level and risk was stronger for cancers of the liver, lung, skin, kidney, and bladder, as well as for lymphoma and leukemia than for other neoplasms.

Conclusions: Our results confirm the important role of inflammation in human cancer and suggest that plasma CRP level is a potential marker of increased cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(2):381–4)
Does “Clock” Matter in Prostate Cancer?
Authors: Zhu Yong , Zheng Tongzhang , Stevens Richard G. , Zhang Yawei , Boyle Peter
Published: March 2006

The ancient adaptation of a 24-hour circadian clock has profound effect on our daily biochemical, physiologic, and behavioral processes, including the monitoring of sex hormone levels. Although the disruption of the circadian cycle has been implicated in the etiology of hormone-related female breast cancer, few studies have been undertaken to determine if a link exists in the development of the most common cancer type among men whose etiology remains largely unknown: hormone-related prostate cancer. Here, we hypothesize that both altered-lighted environments and genetic variations in genes responsible for maintaining circadian rhythms may result in deregulation of clock-associated biological processes, such as androgen expression, and consequently influence an individual's risk of prostate cancer. There is also a potential for the interaction of genetic variants and exposures, such as evening shift work. Confirmation of this hypothesis will add to our understanding of the role of the circadian clock in prostate tumorigenesis and further facilitate the development of novel risk and prognostic biomarkers for prostate cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(1):3–5)
Changes of Gene Expression in Gastric Preneoplasia following Helicobacter pylori Eradication Therapy
Authors: Tsai Chiaojung Jillian , Herrera-Goepfert Roberto , Tibshirani Robert John , Yang Shufang , Mohar Alejandro , Guarner Jeannette , Parsonnet Julie
Published: March 2006

Helicobacter pylori causes gastric preneoplasia and neoplasia. Eradicating H. pylori can result in partial regression of preneoplastic lesions; however, the molecular underpinning of this change is unknown. To identify molecular changes in the gastric mucosa following H. pylori eradication, we used cDNA microarrays (with each array containing ∼30,300 genes) to analyze 54 gastric biopsies from a randomized, placebo-controlled trial of H. pylori therapy. The 54 biopsies were obtained from 27 subjects (13 from the treatment and 14 from the placebo group) with chronic gastritis, atrophy, and/or intestinal metaplasia. Each subject contributed one biopsy before and another biopsy 1 year after the intervention. Significant analysis of microarrays (SAM) was used to compare the gene expression profiles of pre-intervention and post-intervention biopsies. In the treatment group, SAM identified 30 genes whose expression changed significantly from baseline to 1 year after treatment (0 up-regulated and 30 down-regulated). In the placebo group, the expression of 55 genes differed significantly over the 1-year period (32 up-regulated and 23 down-regulated). Five genes involved in cell-cell adhesion and lining (TACSTD1 and MUC13), cell cycle differentiation (S100A10), and lipid metabolism and transport (FABP1 and MTP) were down-regulated over time in the treatment group but up-regulated in the placebo group. Immunohistochemistry for one of these differentially expressed genes (FABP1) confirmed the changes in gene expression observed by microarray. In conclusion, H. pylori eradication may stop or reverse ongoing molecular processes in the stomach. Further studies are needed to evaluate the use of these genes as markers for gastric cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(2):272–80)
Clinical Stage of Breast Cancer by Parity, Age at Birth, and Time Since Birth: A Progressive Effect of Pregnancy Hormones?
Authors: Albrektsen Grethe , Heuch Ivar , Thoresen Steinar , Kvåle Gunnar
Published: March 2006

Breast cancer diagnosed during pregnancy or 1 to 2 years after birth often occurs at a late stage. Little is known about tumor characteristics in the high-risk period shortly after a childbirth. We here explore whether stage of disease differs according to timing of births. Results are based on 22,351 Norwegian breast cancer patients of parity 0 to 5, ages 20 to 74 years. The proportion of stage II to IV tumors was considerably higher among parous than nulliparous women at age <30 years (52.7% versus 36.8%, P = 0.009), but similar or lower in other age groups (Pinteraction = 0.029). In general, the largest proportion of stage II to IV tumors was found among women diagnosed during pregnancy or <2 years after birth. However, among women with late-age births (first or second birth ≥30 years, third birth ≥35 years), as well as women with an early second birth (<25 years), the proportion with advanced disease was rather similar or even higher among those diagnosed 2 to 6 years after birth (49.3-56.0%). The association between clinical stage and time since birth reached statistical significance among women with a late first or second birth and among all triparous women (P ≤ 0.032). The subgroups with a high proportion of advanced disease 2 to 6 years after birth corresponded quite well to those previously found to have the most pronounced transient increase in risk after birth. Thus, pregnancy hormones may have a progressive effect on breast cancer tumors in addition to a possible promoting effect. A potential effect of prolactin is discussed. (Cancer Epidemiol Biomarkers Prev 2006;(15)1:65–9)
Leanness, Smoking, and Enhanced Oxidative DNA Damage
Authors: Mizoue Tetsuya , Kasai Hiroshi , Kubo Tatsuhiko , Tokunaga Shoji
Published: March 2006

An increased risk of some forms of cancer, including lung cancer, among lean individuals has been consistent; however, there is a paucity of biological evidence supporting this relation. Subjects analyzed were 177 healthy Japanese workers who participated in a lifestyle intervention study. The levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were measured using an automated high-pressure liquid chromatography and urinary creatinine levels were adjusted for before statistical analysis. A clear inverse association was found between body mass index (BMI) and 8-OHdG levels among smokers [Pearson correlation coefficient (r) = −0.48], and the association did not materially change after adjustment for potential confounding factors. In contrast, no apparent relation was observed between BMI and 8-OHdG levels among nonsmokers (r = −0.12), although lean nonsmokers had a slightly higher mean of 8-OHdG levels compared with nonlean nonsmokers. The interaction of smoking and BMI reached statistical significance (P = 0.04). Leanness may enhance oxidative DNA damage induced by smoking and thus serve as a marker of host susceptibility to smoking-related cancers. (Cancer Epidemiol Biomarkers Prev 2006;15(3):582–5)
Patterns of Colorectal Cancer Screening Uptake among Men and Women in the United States
Authors: Meissner Helen I. , Breen Nancy , Klabunde Carrie N. , Vernon Sally W.
Published: March 2006

Objective: The purpose of this report is to examine (a) gender-specific correlates of colorectal cancer test use using recent national data from 2003 and (b) patterns of colorectal cancer screening by gender and test modality over time.

Methods: We analyze data from the 1987, 1992, 1998, 2000, and 2003 National Health Interview Surveys. Our sample consists of men and women ≥50 years never diagnosed with colorectal cancer and who reported a recent fecal occult blood test and/or endoscopy.

Results: In 2003, both men and women reported higher rates of colonoscopy (32.2% and 29.8%, respectively) than use of FOBT (16.1% and 15.3%, respectively) or sigmoidoscopy (7.6% and 5.9%, respectively). Men reported higher use of endoscopy than women if they had a usual source of health care, had talked to a general doctor, and had two to five visits to the doctor in the past year. Men and women 65 years and older had higher rates of any recommended colorectal cancer test (55.8% and 48.5%, respectively) than persons 50 to 64 years (males, 41.0%; females, 31.4%). Use of colorectal cancer tests also was higher among both genders if they were not Hispanic, had higher educational attainment, were former smokers, had health insurance or a usual source of care, or if they talked to a general doctor. Recent use of colorectal cancer tests has increased since 2000 for both women and men largely due to increased use of colonoscopy.

Conclusions: Colorectal cancer testing is increasing for both men and women, although the prevalence of testing remains higher in men. Our data support previous findings documenting socioeconomic disparities in colorectal cancer test use. Access barriers to screening could be particularly difficult to overcome if colonoscopy becomes the preferred colorectal cancer screening modality. (Cancer Epidemiol Biomarkers Prev 2006;15(2):389–94)
Dietary Selenium Intake and Genetic Polymorphisms of the GSTP1 and p53 Genes on the Risk of Esophageal Squamous Cell Carcinoma
Authors: Cai Lin , Mu Li-Na , Lu Hua , Lu Qing-Yi , You Nai-Chieh Yuko , Yu Shun-Zhang , Le Anh D. , Zhao Jinkou , Zhou Xue-Fu , Marshall James , Heber David , Zhang Zuo-Feng
Published: March 2006

Few studies have assessed potential effect modifications by polymorphisms of susceptibility genes on the association between selenium intake and esophageal squamous cell carcinoma (ESCC). We studied the joint effects of dietary selenium and the GSTP1 and p53 polymorphisms on ESCC risk in a population-based case-control study with 218 ESCC cases and 415 controls in Taixing City, China. Dietary selenium intake was estimated from a food frequency questionnaire with 97 food items. GSTP1 and p53 polymorphisms were detected by RFLP-PCR assays. Logistic regression analyses were done to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Reduced ESCC risk was observed among individuals in the highest quartile of dietary selenium intake (adjusted OR, 0.31; 95% CI, 0.13-0.70) with a dose-dependent gradient (Ptrend = 0.01). The p53 Pro/Pro genotype was associated with increased risk of ESCC compared with the Arg/Arg genotype (adjusted OR, 2.02; 95% CI, 1.19-3.42). When combined with selenium consumption, an obvious increased risk was observed among individuals with the p53 Pro/Pro or GSTP1 Ile/Ile genotype with adjusted ORs of 3.19 (95% CI, 1.74-5.84) and 1.90 (95% CI, 1.03-3.51), respectively. Among smokers and alcohol drinkers, elevation of ESCC risk was more prominent among p53 Pro/Pro individuals who consumed a low level of dietary selenium (adjusted OR, 3.59; 95% CI, 1.49-8.66 for smokers and 6.19; 95% CI, 1.83-20.9 for drinkers). Our study suggests that the effect of dietary selenium on the risk of ESCC may be modulated by tobacco smoking, alcohol drinking, and p53 Pro/Pro and GSTP1 Ile/Ile genotypes. (Cancer Epidemiol Biomarkers Prev 2006;15(2):294–300)
Variation in Incidence and Fatality of Melanoma by Season of Diagnosis in New South Wales, Australia
Authors: Boniol Mathieu , Armstrong Bruce K. , Doré Jean-François
Published: March 2006

Seasonal variation in cutaneous melanoma incidence with a summer peak is poorly understood. It has been hypothesized to be due to increased diagnosis in summer or a late-promoting effect of sun exposure. We analyzed the characteristics of incident cases of cutaneous melanoma and their outcome by season of diagnosis in the population of New South Wales, Australia. Cases of melanoma (25,845 cases; 10,869 females and 14,976 males) were registered by the New South Wales Central Cancer Registry in 1989 to 1998. There was significant seasonal variation in incidence (P < 0.0001, Nam test). The summer to winter ratio was greater for women, younger people, lesions on the limbs, and superficial spreading melanoma. Melanomas were thicker in winter than in summer (medians 0.75 and 0.70 mm, respectively; P < 0.0001, Kruskal-Wallis test). Cases were followed for a median of 63 months and 2,710 (10.5%) died from their melanoma. Fatality from melanoma was lower for melanomas diagnosed in summer than winter (relative fatality = 0.72; 95% confidence interval, 0.65-0.81); the 5-year survival rate was 92.1% for diagnosis in summer and 89.0% for diagnosis in winter. This result remained significant after adjustment for year of diagnosis, age, sex, Breslow thickness, anatomic location, and histologic type (relative fatality = 0.82; 95% confidence interval, 0.72-0.94). Seasonality in melanoma incidence is probably caused mainly by increased and earlier diagnosis in summer, although a late-stage promotional effect of sun exposure cannot be excluded completely. Earlier diagnosis may also reduce fatality when melanoma is diagnosed in summer. Independence of variation in fatality with season from seasonal variation in thickness, however, suggests that sun exposure around the time of diagnosis decreases fatality of melanoma. (Cancer Epidemiol Biomarkers Prev 2006;15(3):524–8)
Breast and Ovarian Cancer in Relatives of Cancer Patients, with and without BRCA Mutations
Authors: Lee Jennifer S. , John Esther M. , McGuire Valerie , Felberg Anna , Ostrow Kimberly L. , DiCioccio Richard A. , Li Frederick P. , Miron Alexander , West Dee W. , Whittemore Alice S.
Published: March 2006

Background: First-degree relatives of patients with breast or ovarian cancer have increased risks for these cancers. Little is known about how their risks vary with the patient's cancer site, carrier status for predisposing genetic mutations, or age at cancer diagnosis.

Methods: We evaluated breast and ovarian cancer incidence in 2,935 female first-degree relatives of non-Hispanic White female patients with incident invasive cancers of the breast (n = 669) or ovary (n = 339) who were recruited from a population-based cancer registry in northern California. Breast cancer patients were tested for BRCA1 and BRCA2 mutations. Ovarian cancer patients were tested for BRCA1 mutations. We estimated standardized incidence ratios (SIR) and 95% confidence intervals (95% CI) for breast and ovarian cancer among the relatives according to the patient's mutation status, cancer site, and age at cancer diagnosis.

Results: In families of patients who were negative or untested for BRCA1 or BRCA2 mutations, risks were elevated only for the patient's cancer site. The breast cancer SIR was 1.5 (95% CI, 1.2-1.8) for relatives of breast cancer patients, compared with 1.1 (95% CI, 0.8-1.6) for relatives of ovarian cancer patients (P = 0.12 for difference by patient's cancer site). The ovarian cancer SIR was 0.9 (95% CI, 0.5-1.4) for relatives of breast cancer patients, compared with 1.9 (95% CI, 1.0-4.0) for relatives of ovarian cancer patients (P = 0.04 for difference by site). In families of BRCA1-positive patients, relatives' risks also correlated with the patient's cancer site. The breast cancer SIR was 10.6 (95% CI, 5.2-21.6) for relatives of breast cancer patients, compared with 3.3 (95% CI, 1.4-7.3) for relatives of ovarian cancer patients (two-sided P = 0.02 for difference by site). The ovarian cancer SIR was 7.9 (95% CI, 1.2-53.0) for relatives of breast cancer patients, compared with 11.3 (3.6-35.9) for relatives of ovarian cancer patients (two-sided P = 0.37 for difference by site). Relatives' risks were independent of patients' ages at diagnosis, with one exception: In families ascertained through a breast cancer patient without BRCA mutations, breast cancer risks were higher if the patient had been diagnosed before age 40 years.

Conclusion: In families of patients with and without BRCA1 mutations, breast and ovarian cancer risks correlate with the patient's cancer site. Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patient's age at diagnosis. These patterns support the presence of genes that modify risk specific to cancer site, in both carriers and noncarriers of BRCA1 and BRCA2 mutations. (Cancer Epidemiol Biomarkers Prev 2006;15(2):359–63)
TheAIB1Polyglutamine Repeat Does Not Modify Breast Cancer Risk inBRCA1andBRCA2Mutation Carriers
Authors: Spurdle Amanda B. , Antoniou Antonis C. , Kelemen Livia , Holland Helene , Peock Susan , Cook Margaret R. , Smith Paula L. , Greene Mark H. , Simard Jacques , Plourde Marie , Southey Melissa C. , Godwin Andrew K. , Beck Jeanne , Miron Alexander , Daly Mary B. , Santella Regina M. , Hopper John L. , John Esther M. , Andrulis Irene L. , Durocher Francine , Struewing Jeffery P. , Easton Douglas F. , Chenevix-Trench Georgia ,   Australian Breast Cancer Family Study,   Australian Jewish Breast Cancer Study,   Breast Cancer Family Registry,   Interdisciplinary Health Research International Team on Breast Cancer Susceptibility,   The Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer,   Epidemiological Study of Familial Breast Cancer Study Collaborators
Published: March 2006

This is by far the largest study of its kind to date, and further suggests that AIB1 does not play a substantial role in modifying the phenotype of BRCA1 and BRCA2 carriers. The AIB1 gene encodes the AIB1/SRC-3 steroid hormone receptor coactivator, and amplification of the gene and/or protein occurs in breast and ovarian tumors. A CAG/CAA repeat length polymorphism encodes a stretch of 17 to 29 glutamines in the HR-interacting carboxyl-terminal region of the protein which is somatically unstable in tumor tissues and cell lines. There is conflicting evidence regarding the role of this polymorphism as a modifier of breast cancer risk in BRCA1 and BRCA2 carriers. To further evaluate the evidence for an association between AIB1 glutamine repeat length and breast cancer risk in BRCA1 and BRCA2 mutation carriers, we have genotyped this polymorphism in 1,090 BRCA1 and 661 BRCA2 mutation carriers from Australia, Europe, and North America. There was no evidence for an increased risk associated with AIB1 glutamine repeat length. Given the large sample size, with more than adequate power to detect previously reported effects, we conclude that the AIB1 glutamine repeat does not substantially modify risk of breast cancer in BRCA1 and BRCA2 mutation carriers. (Cancer Epidemiol Biomarkers Prev 2006;15(1):76–9)
Prediagnostic Circulating Antibodies to JC and BK Human Polyomaviruses and Risk of Non-Hodgkin Lymphoma
Authors: Rollison Dana E. , Engels Eric A. , Halsey Neal A. , Shah Keerti V. , Viscidi Raphael P. , Helzlsouer Kathy J.
Published: March 2006

Viral infections have been associated with increased risk of non–Hodgkin's lymphoma (NHL). We conducted a nested case-control study to investigate the association between prediagnostic serum antibodies to the human polyomaviruses, JC (JCV) and BK (BKV), and subsequent risk of NHL. Two research serum banks were established in Washington County, Maryland, in 1974 and 1989, with the collection of blood samples from >45,000 volunteers. Incident NHL cases diagnosed through 2002 (n = 170) were identified among participants by linkage to population-based cancer registries. Two controls were matched to each case (n = 340) on age, sex, and blood draw date. Prediagnostic IgG antibodies to JCV and BKV were measured using virus-like particle ELISA. Associations between JCV and BKV antibody seropositivity and NHL were estimated using conditional logistic regression. Overall, neither antibodies to JCV [odds ratio (OR), 0.83; 95% confidence interval (95% CI), 0.56-1.23] nor BKV (OR, 0.98; 95% CI, 0.64-1.48) were associated with an increased risk of NHL. Results were similar after stratification by NHL subtype or induction period and adjustment for EBV seropositivity. Among those who donated blood in both 1974 and 1989, an increase in JCV antibody levels over time was associated with a 4-fold increased risk of NHL compared with a steep decline in antibody levels (OR, 4.59; 95% CI, 1.30-16.25; Ptrend = 0.02). Whereas JCV seropositivity was not associated with NHL overall, the finding of an increased risk of NHL associated with increasing antibody levels among those who were seropositive at baseline warrants further research into factors influencing reactivation of JCV infection. (Cancer Epidemiol Biomarkers Prev 2006;15(3):543–50)
Nucleotide Excision Repair Gene Polymorphisms and Risk of Advanced Colorectal Adenoma:XPCPolymorphisms Modify Smoking-Related Risk
Authors: Huang Wen-Yi , Berndt Sonja I. , Kang Daehee , Chatterjee Nilanjan , Chanock Stephen J. , Yeager Meredith , Welch Robert , Bresalier Robert S. , Weissfeld Joel L. , Hayes Richard B.
Published: March 2006

Objectives: Nucleotide excision repair enzymes remove bulky damage caused by environmental agents, including carcinogenic polycyclic aromatic hydrocarbons found in cigarette smoke, a risk factor for colorectal adenoma. Among participants randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we studied the risk of advanced colorectal adenoma in relation to cigarette smoking and selected single nucleotide polymorphisms (SNP) in the nucleotide excision repair pathway.

Methods: Cases (n = 772) were subjects with left-sided advanced adenoma (>1 cm in size, high-grade dysplasia, or villous characteristics). Controls (n = 777) were screen-negative for left-sided polyps by sigmoidoscopy. DNA was extracted from blood samples and 15 common nonsynonymous SNPs in seven-nucleotide excision repair genes [XPC, RAD23B (hHR23B), CSB (ERCC6), XPD (ERCC2), CCNH, XPF (ERCC4), and XPG (ERCC5)] were genotyped.

Results: None of the studied SNPs were independently associated with advanced adenoma risk. Smoking was related to adenoma risk and XPC polymorphisms (R492H, A499V, K939Q) modified these effects (Pinteraction from 0.03-0.003). Although the three XPC variants were in linkage disequilibrium, a multivariate logistic regression tended to show independent protective effects for XPC 499V (Ptrend = 0.06), a finding supported by haplotype analysis (covariate-adjusted global permutation P = 0.03).

Conclusions: Examining a spectrum of polymorphic variants in nucleotide excision repair genes, we found evidence that smoking-associated risks for advanced colorectal adenoma are modified by polymorphisms in XPC, particularly haplotypes containing XPC 499V. (Cancer Epidemiol Biomarkers Prev 2006;15(2):306–11)
Risk of Colorectal Cancer in Monoallelic and Biallelic Carriers of MYH Mutations: A Population-Based Case-Family Study
Authors: Jenkins Mark A. , Croitoru Marina E. , Monga Neerav , Cleary Sean P. , Cotterchio Michelle , Hopper John L. , Gallinger Steven
Published: March 2006

Previous case-control studies have suggested that carriers of monoallelic germline mutations in the MYH gene may be at increased risk of colorectal cancer. We applied a kin-cohort design, using a modified segregation analysis, to estimate the colorectal cancer risk using 300 first-degree relatives of 39 colorectal cancer cases who were monoallelic or biallelic carriers of MYH mutations. We found that monoallelic carriers had a 3-fold increased risk of colorectal cancer (hazard ratio, 2.9; 95% confidence interval, 1.2-7.0; P = 0.02) and biallelic carriers a 50-fold increased risk (hazard ratio, 53; 95% confidence interval, 14-200; P < 0.0001). This analysis illustrates the potential of family analysis to estimate cancer risk for low-frequency mutations and, based on the proportion of relatives predicted to be carriers, we believe that this constitutes the largest study of monoallelic carriers to date. (Cancer Epidemiol Biomarkers Prev 2006;15(2):312–4)
Cigarette Smoking and Lung Cancer: Modeling Total Exposure and Intensity
Authors: Lubin Jay H. , Caporaso Neil E.
Published: March 2006

Investigators typically analyze cigarette smoking using smoking duration and intensity (number of cigarettes smoked per day) as risk factors. However, odds ratios (OR) for categories of intensity either adjusted for, or jointly with, duration of smoking may be distorted by differences in total pack-years of exposure to cigarette smoke. To study effects of intensity, we apply a linear excess OR model to compare total exposure delivered at low intensity for a long period of time with an equal total exposure delivered at high intensity for a short period of time to data from a large case-control study of lung cancer. The excess OR per pack-year increases with intensity for subjects who smoke ≤20 cigarettes per day and decreases with intensity for subjects who smoke >20 cigarettes per day. The intensity patterns are homogeneous by histologic type of lung cancer, suggesting that observed differences in risks by histologic type are related to total smoking exposure or smoking duration and not smoking intensity. At lower smoking intensities, there is an “exposure enhancement” effect such that for equal total exposure, the excess OR per pack-year increases with intensity. At higher smoking intensities, there is a “reduced potency” or “wasted exposure” effect such that for equal total exposure, the excess OR per pack-year decreases with intensity (i.e., smoking at a lower intensity for longer duration is more deleterious than smoking at a higher intensity for shorter duration). (Cancer Epidemiol Biomarkers Prev 2006;15(3):517–23)