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Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk. [ABSTRACT FROM AUTHOR]

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. [ABSTRACT FROM AUTHOR]

Objective: Multivitamins contain several nutrients, including folic acid, which are hypothesized to reduce colon cancer risk. Previous epidemiologic studies have suggested that effects of multivitamins containing substantial amounts of folic acid (introduced in 1973) may not be evident until 15 or more years since first use.Methods: We examined the association between daily multivitamin use and colon cancer mortality among 806,397 US men and women in the Cancer Prevention Study II cohort who completed a questionnaire at enrollment in 1982 and were followed for mortality through 1998.Results: After multivariate adjustment, multivitamin use at enrollment showed little association with colon cancer mortality. After 15 years since first use of a multivitamin potentially containing folic acid, we observed slightly decreased risk of colon cancer mortality (rate ratio (RR) = 0.89, 95% confidence interval (CI) 0.80-0.99). Consistent with previous reports, this association was stronger among participants consuming two or more alcoholic drinks per day (RR = 0.71, 95% CI 0.56-0.91).Conclusion: Our results are consistent with a modest reduction in colon cancer mortality associated with use of folic acid-containing multivitamins among moderate to heavy alcohol users. [ABSTRACT FROM AUTHOR]

Objective: To investigate the hypothesis that alcohol consumption increases the risk of breast cancer mortality.Methods: We examined breast cancer mortality in relation to self-reported alcohol consumption in women from the American Cancer Society Cancer Prevention Study (CPS)-II. After 14 years of follow-up, 1,442 eligible breast cancer deaths were observed among 242,010 women. Cox proportional hazards models were constructed for total alcohol consumption and for beer, wine, and liquor separately.Results: Total alcohol consumption was associated with increased risk of fatal breast cancer among post- but not pre- or perimenopausal women. Even less than one drink/day was associated with up to a 30% increase in breast cancer mortality among postmenopausal women compared to non-drinkers (RR = 1.3, 95% CI: 1.1-1.6 for women drinking 0.26-<1 drink/day). When examined separately, consumption of beer, wine, and liquor each increased the risk of breast cancer among postmenopausal women. We found no evidence that alcohol consumption was more deleterious among women at high risk for breast cancer compared to average-risk women.Conclusion: This study adds to the evidence that postmenopausal women can reduce their risk of breast cancer by avoiding or minimizing their use of alcohol. [ABSTRACT FROM AUTHOR]

Objective: To investigate the hypothesis that tubal sterilization is associated with a reduced risk of breast cancer.Methods: We examined this hypothesis in a large prospective study of US adults. After 14 years of mortality follow-up, 3837 deaths from breast cancer were observed in a cohort of 619,199 women who were cancer-free at study entry in 1982.Results: Cox proportional hazards models (adjusted for multiple breast cancer risk factors) showed a significant inverse association between tubal sterilization and breast cancer mortality (adjusted rate ratio (RR) = 0.82, 95% confidence interval (CI) 0.70-0.96). Women who were sterilized before age 35 had a lower risk (adjusted RR = 0.69, 95% CI 0.53-0.88) than women who were sterilized at 35 years of age or older (adjusted RR = 0.92, 95% CI 0.75-1.13). Also, sterilizations performed before 1975 resulted in a lower risk (RR = 0.75, 95% CI 0.62-0.91) than those performed during or after 1975 (RR = 0.98, 95% CI 0.74-1.29), possibly reflecting the likelihood of greater tissue damage with earlier procedures.Conclusions: These results suggest that tubal sterilization may lower subsequent risk of breast cancer, especially among women who are sterilized at a relatively young age. Additional studies are needed to confirm or refute these findings. [ABSTRACT FROM AUTHOR]

Objectives: Cigarette smoking is considered an important risk factor for pancreatic cancer, but other purported risk factors are less well established. To learn more about the epidemiology of this important cause of mortality we examined associations with a variety of possible risk factors for death from pancreatic cancer in a large, prospective study of United States adults.Methods: We used proportional hazards models to obtain adjusted estimates of relative risks (hazards ratios). During 14 years of follow-up, 3751 persons died of pancreatic cancer in a cohort of 483,109 men and 619,199 women who had no reported history of cancer at enrollment in 1982.Results: Cigarette smoking at baseline was associated with fatal pancreatic cancer among men (multivariate relative risk [RR] = 2.1, 95% confidence interval [CI] 1.9-2.4) and among women (RR = 2.0, 95% CI 1.8-2.3). A trend in risk was observed with increasing number of cigarettes smoked per day among current smokers at baseline. With several variables included in separate models for men and women, we found additional factors to be predictive of pancreatic cancer mortality, including family history of pancreatic cancer, black race, diabetes, and increased body mass index. History of gallstones was predictive of pancreatic cancer among men. An inverse association with vegetable consumption was observed among men, that was not statistically significant.Conclusion: Our findings confirm that cigarette smoking is an important predictor of pancreatic cancer mortality, and identify several other factors that may contribute to increased risk. [ABSTRACT FROM AUTHOR]

Objectives: Diabetes mellitus and pancreatic cancer are known to be associated, but it is not known whether diabetes is a true risk factor, preceding development of the cancer, or if it is an early manifestation of the cancer. To address this uncertainty, we examined the association of pancreatic cancer mortality and reported diabetes of at least one year's duration in a large, prospective study of United States adults. The vast majority of diabetes in this cohort is likely to be non-insulin-dependent diabetes.Methods: After 12 years of follow-up, 2,953 deaths from pancreatic cancer were observed in a cohort of 1,089,586 men and women who were cancer-free at study entry in 1982. Cox proportional hazards models, adjusted for age, race, smoking, family history of pancreatic cancer, body mass index (wt/ht2), and education, were used to assess associations.Results: A history of diabetes was significantly related to pancreatic cancer mortality in both men (rate ratio [RR] = 1.49, 95 percent confidence interval [CI] = 1.25-1.77) and women (RR = 1.51, CI = 1.24-1.85). However, the strength of the association varied over the follow-up period. The death rate from pancreatic cancer was twice as high in diabetics as in non-diabetics during the second and third years of follow-up (adjusted RR = 2.05, CI = 1.56-2.69) but only about 40 percent higher in years nine to 12 (adjusted RR = 1.38, CI = 1.08-1.77).Conclusions: The small but persistent increased risk of death from pancreatic cancer, seen even when the diagnosis of diabetes preceded death by many years, supports the hypothesis that diabetes may be a true, albeit modest, risk factor for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Objectives: It is difficult to separate the possible role of fertility drugs from underlying infertility as risk factors for ovarian cancer. The present study examined the relationship between self-reported infertility and death from ovarian cancer among married women unlikely to have been exposured to fertility drugs.Methods: Women were selected for study from the 676,526 female participants in Cancer Prevention Study II (CPS-II). After twelve years of follow-up, 797 deaths from ovarian cancer were observed among women with no prior history of cancer or hysterectomy and 40 years of age or older in 1967 when ovulatory stimulants were approved in the United States. Cox proportional hazards modeling was used to compute rate ratios (RRs) and to adjust for other potential risk factors.Results: Overall, self-reported infertility was not significantly associated with ovarian cancer mortality (adjusted rate ratio (RR) = 1.1, 95 percent confidence interval (CI) = 0.9-1.3). Ovarian cancer death rates among nulligravid women with self-reported infertility, however, were 40 percent higher than for nulligravid women who never tried to become pregnant (RR = 1.4, 95 percent CI = 0.9-2.4). Multigravid women who reported infertility problems were not at increased risk.Conclusions: These results suggest that infertility itself, without concomitant exposure to fertility drugs, may increase risk of fatal ovarian cancer among nulligravid women. [ABSTRACT FROM AUTHOR]

To evaluate the relationship between breast cancer risk and spontaneous and induced abortion, we conducted a detailed descriptive review of 32 epidemiologic studies that provided data by type of abortion and by various measures of exposure to abortion-number of abortions, timing of abortion in relation to first full-term pregnancy, length of gestation, and age at first abortion. Breast cancer risk did not appear to be associated with an increasing number of spontaneous or induced abortions. Our review also suggested that breast cancer risk probably was not related to the other measures of exposure to abortion, and probably did not differ by age or a family history of breast cancer. Finally, the data appeared to suggest a slightly increased risk among nulliparous women, but this tendency was based primarily on studies with a small number of nulliparous women who had had spontaneous or induced abortions. Definitive conclusions about an association between breast cancer risk and spontaneous or induced abortion are not possible at present because of inconsistent findings across studies. Future investigations should consider prospective designs, separate analyses of spontaneous and induced abortions, appropriate referent groups, and adequate adjustment for confounding and effect modification. Future investigations also should attempt to determine whether any increased risks reflect the transient increase in breast cancer risk hypothesized for full-term pregnancy or a causal relationship specific to spontaneous or induced abortion. [ABSTRACT FROM AUTHOR]