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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]

Background: Recent studies suggest that long-term cigarette smoking is associated with an increased risk of colorectal cancer. Whether the association is causal or due to confounding remains unclear.Methods: We examined cigarette smoking in relation to colorectal cancer mortality, evaluating smoking duration and recency and controlling for potential confounders in the Cancer Prevention Study II. This prospective nationwide mortality study of 1 184 657 adults (age > or =30 years) was begun by the American Cancer Society in 1982. After exclusions, our analytic cohort included 312 332 men and 469 019 women, among whom 4432 colon or rectal cancer deaths occurred between 1982 and 1996 among individuals who were cancer free in 1982. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated by fitting Cox proportional hazards models. All statistical tests were two-sided.Results: Multivariate-adjusted colorectal cancer mortality rates were highest among current smokers, were intermediate among former smokers, and were lowest in lifelong nonsmokers. The multivariate-adjusted RR (95% CI) for current compared with never smokers was 1.32 (1.16-1.49) among men and 1.41 (1.26-1.58) among women. Increased risk was evident after 20 or more years of smoking for men and women combined as compared with never smokers. Risk among current and former smokers increased with duration of smoking and average number of cigarettes smoked per day; risk in former smokers decreased significantly with years since quitting. If the multivariate-adjusted RR estimates in this study do, in fact, reflect causality, then approximately 12% of colorectal cancer deaths among both men and women in the general U.S. population in 1997 were attributable to smoking.Conclusions: Long-term cigarette smoking is associated with increased risk of colorectal cancer mortality in both men and women. Clear reduction in risk is observed with early smoking cessation. [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]

Background: Several studies have reported positive associations between environmental tobacco smoke (ETS) and increased risk of breast cancer. However, studies of active smoking and risk of breast cancer are equivocal and in general do not support a positive association. To try to resolve this paradox, we examined the association between breast cancer mortality and potential ETS exposure from spousal smoking in an American Cancer Society prospective study of U.S. adult women.Methods: We assessed breast cancer death rates in a cohort of 146 488 never-smoking, single-marriage women who were cancer free at enrollment in 1982. Breast cancer death rates among women whose husbands smoked were compared with those among women married to men who had never smoked. Cox proportional hazards modeling was used to control for potential risk factors other than ETS exposure.Results: After 12 years of follow-up, 669 cases of fatal breast cancer were observed in the cohort. Overall, we saw no association between exposure to ETS and death from breast cancer (rate ratio [RR] = 1.0; 95% confidence interval [CI] = 0.8-1.2). We did, however, find a small, not statistically significant increased risk of breast cancer mortality among women who were married before age 20 years to smokers (RR = 1. 2; 95% CI = 0.8-1.8).Conclusions: In contrast to the results of previous studies, this study found no association between exposure to ETS and female breast cancer mortality. The results of our study are particularly compelling because of its prospective design as compared with most earlier studies, the relatively large number of exposed women with breast cancer deaths, and the reporting of exposure by the spouse rather than by proxy. [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]

Frequent consumption of fruits, vegetables, and whole grains has been associated with a reduced risk of stomach cancer in the majority of case-control studies of these factors: however, prospective studies have been less consistent. We examined the association between selected major food groups (citrus fruits, vegetables, whole grains, and processed meats) and risk of fatal stomach cancer in the Cancer Prevention Study (CPS) II cohort of 1.2 million United States men and women. During 14 years of follow-up, we documented 439 stomach cancer deaths in women and 910 in men after exclusion of individuals with prevalent cancers, inadequate diet information, and recent weight loss at baseline in 1982. After controlling for other risk factors, none of the food groups examined were associated with risk of stomach cancer except for an unexpected increased risk with vegetable consumption in women [relative risk (RR) = 1.25; 95% confidence interval (CI), 0.99-1.58; highest versus lowest tertile, P = 0.06 for trend]. A high overall plant food intake (a sum of vegetables, citrus fruit, and whole grains) was associated with reduced risk in men (RR = 0.79; 95% CI, 0.67-0.93; highest versus lowest tertile, P = 0.003 for trend), but not in women (RR = 1.18; 95% CI, 0.93-1.50; P = 0.16 for trend). Of individual foods examined, liver consumption greater than twice/week was associated with an increased risk of fatal stomach cancer in women (RR = 1.96; 95% CI, 1.09-3.53) and men (RR = 1.63; 95% CI, 1.02-2.62) compared with nonconsumers. This study supports a modest role for plant foods in reducing the risk of fatal stomach cancer in men, but not in women.

Buccal cells are becoming an important source of genomic DNA in epidemiological studies, but little is known about the effect of different sampling conditions on DNA quality and yield. We used a mouthwash protocol to collect six daily buccal cell samples from 35 healthy volunteers. Twenty-four individuals (six men and 18 women) correctly completed the protocol and were included in paired analyses to determine whether "swish" time (30 s versus 60 s), toothbrushing before collection, or lag time between collection and DNA extraction (1 day versus 5, 10, or 30 days at room temperature) would affect sample quality and yield. Total DNA, human-specific DNA (hDNA), degradation of DNA, and ability to amplify by PCR were determined. hDNA yield did not significantly vary by "swish" time. However, toothbrushing 1 h before sample collection reduced the amount of hDNA by nearly 40% (34 microg versus 21 microg; P = 0.06). Median hDNA yields for samples that were held for 1, 5, 10, and 30 days before extraction were 32 microg (range, 4-196), 32 microg (2-194), 23 microg (3-80), and 21 microg (5-56), respectively. The 10- and 30-day samples had significantly less hDNA than those processed after 1 day (P = 0.01). PCR success rates for beta-globin gene fragments of length 268 bp, 536 bp, and 989 bp were 94% or better, and high molecular weight DNA (>23 kb) was found in all but one sample. These results suggest that buccal cells should be collected before brushing teeth and processed within 5 days of collection to maximize hDNA yield.

The authors evaluated the association between use of individual supplements of vitamins A, C, and E only and multivitamins and fatal non-Hodgkin's lymphoma in a large prospective mortality study of US men and women. During 14 years of follow-up (1982-1996), 1,571 non-Hodgkin's lymphoma deaths among 508,351 men and 1,398 non-Hodgkin's lymphoma deaths among 676,306 women were documented. Long-term regular use of individual supplements of vitamins A, C, and E only and multivitamins was unrelated to fatal non-Hodgkin's lymphoma among either men or women. The multivariate relative risks for men who used supplements for 10 or more years were 1.03 (95% confidence interval (CI): 0.54, 2.00) for vitamin A supplements, 1.04 (95% CI: 0.78, 1.39) for vitamin C supplements, 1.06 (95% CI: 0.74, 1.51) for vitamin E supplements, and 1.14 (95% CI: 0.92, 1.40) for multivitamins. The multivariate relative risks for women who used supplements for 10 or more years were 1.40 (95% CI: 0.77, 2.54) for vitamin A supplements, 1.19 (95% CI: 0.89, 1.60) for vitamin C supplements, 1.27 (95% CI: 0.87, 1.84) for vitamin E supplements, and 1.21 (95% CI: 0.98, 1.50) for multivitamins. All associations became weaker when vitamin supplements were mutually adjusted. These findings do not support an important relation between long-term regular use of individual supplements of vitamins A, C, and E only and multivitamins and fatal non-Hodgkin's lymphoma.

Body weight and height have both been associated consistently with postmenopausal breast cancer but less consistently with prostate cancer. The present study examined the relationship between body mass index (BMI), height, and death from prostate cancer in two large American Cancer Society cohorts. Men in the study were selected from the male participants in Cancer Prevention Study I (CPS-I; enrolled in 1959 and followed through 1972) and Cancer Prevention Study II (CPS-II; enrolled in 1982 and followed through 1996). After exclusions, 1,590 prostate cancer deaths remained among 381,638 men in CPS-I and 3,622 deaths among 434,630 men in CPS-II. Cox proportional hazards modeling was used to compute rate ratios (RR) and to adjust for confounders. Prostate cancer mortality rates were significantly higher among obese (BMI, > or =30) than nonobese (BMI, <25) men in both cohorts [adjusted RR, 1.27; 95% confidence interval (CI), 1.04-1.56 in CPS-I; RR, 1.21; 95% CI, 1.07-1.37 in CPS-II]. Prostate cancer mortality rates in the CPS-I cohort were lowest for the shortest men (RR, 0.80; 95% CI, 0.63-1.03 for men <65 inches versus 65-66 inches) and highest for the tallest men (RR, 1.39; 95% CI, 1.11-1.74 for men > or =73 inches tall versus 65-66 inches). Rates remained constant among men 65-72 inches tall. No association between height and prostate cancer mortality was observed in the CPS-II cohort (RR, 1.03; 95% CI, 0.82-1.29 for men > or =75 versus 65-66 inches). These results support the hypothesis that obesity increases risk of prostate cancer mortality. Decreased survival among obese men may be a likely explanation for this association.

Context: Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2 hormone-related cancers. The effect of postmenopausal estrogen use on ovarian cancer is not established., Objectives: To examine the association between postmenopausal estrogen use and ovarian cancer mortality and to determine whether the association differs according to duration and recency of use., Design and Setting: The American Cancer Society's Cancer Prevention Study II, a prospective US cohort study with mortality follow-up from 1982 to 1996., Participants: A total of 211 581 postmenopausal women who completed a baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or ovarian surgery at enrollment., Main Outcome Measure: Ovarian cancer mortality, compared among never users, users at baseline, and former users as well as by total years of use of estrogen replacement therapy (ERT)., Results: A total of 944 ovarian cancer deaths were recorded in 14 years of follow-up. Women who were using ERT at baseline had higher death rates from ovarian cancer than never users (rate ratio [RR], 1.51; 95% confidence interval [CI], 1.16-1.96). Risk was slightly but not significantly increased among former estrogen users (RR, 1.16; 95% CI, 0.99-1.37). Duration of use was associated with increased risk in both baseline and former users. Baseline users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17), while former users with 10 or more years of use had an RR of 1.59 (95% CI, 1.13-2.25). Annual age-adjusted ovarian cancer death rates per 100 000 women were 64.4 for baseline users with 10 or more years of use, 38.3 for former users with 10 or more years of use, and 26.4 for never users. Among former users with 10 or more years of use, risk decreased with time since last use reported at study entry (RR for last use <15 years ago, 2.05; 95% CI, 1.29-3.25; RR for last use >/=15 years ago, 1.31; 95% CI, 0.79-2.17)., Conclusions: In this population, postmenopausal estrogen use for 10 or more years was associated with increased risk of ovarian cancer mortality that persisted up to 29 years after cessation of use.

In observational studies, estrogen replacement therapy is associated with decreased cardiovascular disease rates and increased breast cancer rates. Recent evidence suggests that the impact of estrogen use on disease outcomes may vary by body mass. In a prospective study of 290,827 postmenopausal US women with no history of cancer or cardiovascular disease at enrollment in 1982, the authors examined the association between postmenopausal estrogen use and all-cause, coronary heart disease, stroke, all-cancer, and breast cancer death rates and whether these associations differed by body mass. After 12 years of follow-up, results from Cox proportional hazards models showed that all-cause death rates were lower among baseline estrogen users than never users (rate ratio (RR) = 0.82, 95% confidence interval (CI): 0.78, 0.87). The lowest relative risk was found for coronary heart disease (RR = 0.66, 95% CI: 0.58, 0.77). The inverse association between estrogen use and coronary heart disease mortality was strongest for thin women (body mass index <22 kg/m2) (RR = 0.49, p for interaction = 0.02). Breast cancer mortality did not increase with estrogen use overall, and no increased risk was observed for thin or heavy women. In this population, the reduction in coronary heart disease mortality among estrogen users was greatest for thinner women. Additional studies are needed to confirm or refute these results.

Some recent epidemiological studies have suggested that use of vitamin C or vitamin E supplements, both of which are important antioxidants, may substantially reduce the risk of colon or colorectal cancer. We examined the association between colorectal cancer mortality and use of individual vitamin C and E supplements in the American Cancer Society's Cancer Prevention Study II cohort. We used proportional hazards modeling to estimate rate ratios among 711,891 men and women in the United States who completed a self-administered questionnaire at study enrollment in 1982, had no history of cancer, and were followed for mortality through 1996. During the 14 years of follow-up, 4404 deaths from colorectal cancer occurred. After adjustment for multiple colorectal cancer risk factors, regular use of vitamin C or E supplements, even long-term use, was not associated with colorectal cancer mortality. The combined-sex rate ratios were 0.89 [95% confidence interval (CI), 0.73-1.09] for 10 or more years of vitamin C use and 1.08 (95% CI, 0.85-1.38) for 10 or more years of vitamin E use. In subgroup analyses, use of vitamin C supplements for 10 or more years was associated with decreased risk of colorectal cancer mortality before age 65 years (rate ratio = 0.48; 95% CI, 0.28-0.81) and decreased risk of rectal cancer mortality at any age (rate ratio = 0.40; 95% CI, 0.20-0.80). Our results do not support a substantial effect of vitamin C or E supplement use on overall colorectal cancer mortality.

Background: Recent studies suggest that long-term cigarette smoking is associated with an increased risk of colorectal cancer. Whether the association is causal or due to confounding remains unclear., Methods: We examined cigarette smoking in relation to colorectal cancer mortality, evaluating smoking duration and recency and controlling for potential confounders in the Cancer Prevention Study II. This prospective nationwide mortality study of 1 184 657 adults (age > or =30 years) was begun by the American Cancer Society in 1982. After exclusions, our analytic cohort included 312 332 men and 469 019 women, among whom 4432 colon or rectal cancer deaths occurred between 1982 and 1996 among individuals who were cancer free in 1982. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated by fitting Cox proportional hazards models. All statistical tests were two-sided., Results: Multivariate-adjusted colorectal cancer mortality rates were highest among current smokers, were intermediate among former smokers, and were lowest in lifelong nonsmokers. The multivariate-adjusted RR (95% CI) for current compared with never smokers was 1.32 (1.16-1.49) among men and 1.41 (1.26-1.58) among women. Increased risk was evident after 20 or more years of smoking for men and women combined as compared with never smokers. Risk among current and former smokers increased with duration of smoking and average number of cigarettes smoked per day; risk in former smokers decreased significantly with years since quitting. If the multivariate-adjusted RR estimates in this study do, in fact, reflect causality, then approximately 12% of colorectal cancer deaths among both men and women in the general U.S. population in 1997 were attributable to smoking., Conclusions: Long-term cigarette smoking is associated with increased risk of colorectal cancer mortality in both men and women. Clear reduction in risk is observed with early smoking cessation.

Women tend to fear breast cancer and thus overestimate their risk of developing it, have less concern about developing heart disease, and do not know that lung cancer is the major cause of cancer death. Death certificate data, consolidated into a national database by the National Center for Health Statistics, were used to compare age-specific mortality due to selected cardiovascular diseases and cancers among women who died in 1997 in the United States. The outcomes examined included underlying cause of death categorized as all circulatory system disease, cerebrovascular disease, and heart disease, including coronary and noncoronary disease, and as all cancers combined plus cancer of the lung, breast, and colon/rectum. In 1997, 500,703 women in the United States died from diseases of the circulatory system, including 370,357 deaths from heart disease. Most deaths from heart disease were due to coronary heart disease, which exceeded mortality from cerebrovascular disease at all ages except under age 40. In 1997, 258,463 women in the United States died from cancer, and before age 55, breast cancer death rates exceeded lung and colorectal cancer death rates. Mortality due to total heart disease exceeded breast and lung cancer mortality among women at all ages, but before age 55, when absolute death rates are low, breast cancer death rates exceeded those for coronary heart disease. In conclusion, aside from mortality due to all cancers combined and circulatory system disease, only accidents, which were not included in this study, and total heart disease caused more deaths than breast cancer before age 55.

Obesity has been reported to increase the risk of colon cancer, especially in men. The authors examined this relation in the American Cancer Society's Cancer Prevention Study II, a nationwide mortality study of US adults. After 12 years of follow-up, 1,616 deaths from colon cancer in women and 1,792 in men were observed among 496,239 women and 379,167 men who were cancer free at enrollment in 1982. The authors used Cox proportional hazards analyses to control for effects of age, race, education, smoking, exercise, alcohol, parental history of colon cancer, fat intake, vegetable and grain intake, aspirin use and, in women, estrogen replacement therapy. In men, death rates from colon cancer increased across the entire range of body mass index (BMI). The rate ratio was highest for men with BMI > or =32.5 (rate ratio (RR) = 1.90, 95% confidence interval (CI): 1.46, 2.47) compared with men with BMI between 22.00 and 23.49. In women, a weaker association was seen in the three BMI categories of 27.5-29.9 (RR = 1.26, 95% CI: 1.03, 1.53), 30.0-32.4 (RR = 1.37, 95% CI: 1.09, 1.72), and > or =32.5 (RR = 1.23, 95% CI: 0.96, 1.59). These prospective data support the hypothesis that obesity increases the risk of colon cancer death and that the relation is stronger and more linear in men than in women.

Background: Several studies have reported positive associations between environmental tobacco smoke (ETS) and increased risk of breast cancer. However, studies of active smoking and risk of breast cancer are equivocal and in general do not support a positive association. To try to resolve this paradox, we examined the association between breast cancer mortality and potential ETS exposure from spousal smoking in an American Cancer Society prospective study of U.S. adult women., Methods: We assessed breast cancer death rates in a cohort of 146 488 never-smoking, single-marriage women who were cancer free at enrollment in 1982. Breast cancer death rates among women whose husbands smoked were compared with those among women married to men who had never smoked. Cox proportional hazards modeling was used to control for potential risk factors other than ETS exposure., Results: After 12 years of follow-up, 669 cases of fatal breast cancer were observed in the cohort. Overall, we saw no association between exposure to ETS and death from breast cancer (rate ratio [RR] = 1.0; 95% confidence interval [CI] = 0.8-1.2). We did, however, find a small, not statistically significant increased risk of breast cancer mortality among women who were married before age 20 years to smokers (RR = 1. 2; 95% CI = 0.8-1.8)., Conclusions: In contrast to the results of previous studies, this study found no association between exposure to ETS and female breast cancer mortality. The results of our study are particularly compelling because of its prospective design as compared with most earlier studies, the relatively large number of exposed women with breast cancer deaths, and the reporting of exposure by the spouse rather than by proxy.

Background: Body-mass index (the weight in kilograms divided by the square of the height in meters) is known to be associated with overall mortality. We investigated the effects of age, race, sex, smoking status, and history of disease on the relation between body-mass index and mortality., Methods: In a prospective study of more than 1 million adults in the United States (457,785 men and 588,369 women), 201,622 deaths occurred during 14 years of follow-up. We examined the relation between body-mass index and the risk of death from all causes in four subgroups categorized according to smoking status and history of disease. In healthy people who had never smoked, we further examined whether the relation varied according to race, cause of death, or age. The relative risk was used to assess the relation between mortality and body-mass index., Results: The association between body-mass index and the risk of death was substantially modified by smoking status and the presence of disease. In healthy people who had never smoked, the nadir of the curve for body-mass index and mortality was found at a body-mass index of 23.5 to 24.9 in men and 22.0 to 23.4 in women. Among subjects with the highest body-mass indexes, white men and women had a relative risk of death of 2.58 and 2.00, respectively, as compared with those with a body-mass index of 23.5 to 24.9. Black men and women with the highest body-mass indexes had much lower risks of death (1.35 and 1.21), which did not differ significantly from 1.00. A high body-mass index was most predictive of death from cardiovascular disease, especially in men (relative risk, 2.90; 95 percent confidence interval, 2.37 to 3.56). Heavier men and women in all age groups had an increased risk of death., Conclusions: The risk of death from all causes, cardiovascular disease, cancer, or other diseases increases throughout the range of moderate and severe overweight for both men and women in all age groups. The risk associated with a high body-mass index is greater for whites than for blacks.

Results of two recent prospective incidence studies have suggested that certain subgroups of men with diabetes mellitus may be protected from developing prostate cancer. Two earlier studies, however, concluded that diabetes increased the risk of mortality from prostate cancer. With hundreds of thousands of male respondents, the 1959-1972 Cancer Prevention Study provided a unique opportunity to explore whether men with diabetes were more likely to develop prostate cancer during a 13-year follow-up period than were men without diabetes. After adjusting for factors associated with prostate cancer in previous studies, we found little association between diabetes at baseline and prostate cancer incidence [incidence density ratio (IDR) = 1.05; 95% confidence interval (CI) = 0.81-1.36]. Men who had diabetes mellitus for 5 or more years, however, had a higher incidence of prostate cancer than did men without diabetes (IDR = 1.56; 95% CI = 1.02-2.38). Among all study participants who were diagnosed with prostate cancer, men with diabetes were only slightly more likely to die from prostate cancer than were men without diabetes (IDR = 1.11; 95% CI = 0.76-1.62).

To examine the relation between family history of breast cancer in a mother or sister and a man's risk of fatal prostate cancer, we analyzed data from a prospective mortality study of adult men in the United States. During 12 years of follow-up, there were 3,141 deaths from prostate cancer in a cohort of 480,802 men who were cancer-free at study entry in 1982. Results from Cox proportional hazards models, adjusted for other risk factors, showed a modest increased risk of fatal prostate cancer associated with a family history of breast cancer (in the absence of a family history of prostate cancer) [rate ratio (RR) = 1.16; 95% confidence interval (CI) = 1.01-1.33]. The association was stronger among men younger than 65 years of age whose relatives were diagnosed with breast cancer before age 50 years (RR = 1.65; 95% CI = 0.88-3.10) and among Jewish men (RR = 1.73; 95% CI = 1.00-2.97). The increased risks observed in these subgroups may reflect genetic alterations underlying familial clustering of prostate and breast cancer.

Background: Adenocarcinoma of the lung, once considered minimally related to cigarette smoking, has become the most common type of lung cancer in the United States. The increased incidence of this cancer might be explained by advances in diagnostic technology (i.e., increased ability to perform biopsies on tumors in smaller, more distal airways), changes in cigarette design (e.g., the adoption of filtertips), or changes in smoking practices. We examined data from the Connecticut Tumor Registry and two American Cancer Society studies to explore these possibilities., Methods: Connecticut Tumor Registry data from 1959 through 1991 were analyzed to determine whether the increase in lung adenocarcinoma observed during that period could be best described by birth cohort effects (i.e., generational changes in cigarette smoking) or calendar period effects (i.e., diagnostic advances). Associations between cigarette smoking and death from specific types of lung cancer during the first 2 years of follow-up in Cancer Prevention Study I (CPS-I), initiated in 1959) and Cancer Prevention Study II (CPS-II, initiated in 1982) were also examined., Results: Adenocarcinoma incidence in Connecticut increased nearly 17-fold in women and nearly 10-fold in men from 1959 through 1991. The increases followed a clear birth cohort pattern, paralleling gender and generational changes in smoking more than diagnostic advances. Cigarette smoking became more strongly associated with death from lung adenocarcinoma in CPS-II compared with CPS-I, with relative risks of 19.0 (95% confidence interval [CI] = 8.3-47.7) for men and 8.1 (95% CI = 4.5-14.6) for women in CPS-II and 4.6 (95% CI = 1.7-12.6) for men and 1.5 (0.3-7.7) for women in CPS-I., Conclusions: The increase in lung adenocarcinoma since the 1950s is more consistent with changes in smoking behavior and cigarette design than with diagnostic advances.

The authors examined the relation between smoking and the risk of fatal prostate cancer in a large prospective mortality study of 450,279 men who were cancer free at enrollment in 1982. During 9 years of follow-up, 1,748 deaths occurred from prostate cancer. Cox proportional hazards modeling was used to adjust for other risk factors. Current cigarette smoking was associated with fatal prostate cancer (rate ratio = 1.34, 95% confidence interval (CI) 1.16-1.56). The rate ratio was greater at younger ages, decreasing from 1.83 (95% CI 1.04-3.24) among men below the age of 60 years to 1.11 (95% CI 0.79-1.58) among men aged 80 years and above (p for trend = 0.16). No trend in risk was observed with the number of cigarettes per day or with the duration of smoking among current smokers at baseline, and no increased risk was found among former smokers. Race did not significantly modify the association between cigarette smoking and fatal prostate cancer. These data, together with those of three other large prospective studies that find higher death rates from prostate cancer in current cigarette smokers, and inconsistent findings in incidence studies suggest that smoking may adversely affect survival in prostate cancer patients.

We examined the relation between menstrual irregularity and breast cancer mortality in the American Cancer Society Cancer Prevention Study I. In 1959, 428,653 women age 30 years and older completed a questionnaire on possible cancer risk factors, including their recollection of their menstrual pattern at age 20 years. We used proportional hazards analysis to estimate rate ratios, based on 2,226 breast cancer deaths over 13 years of follow-up. Women who reported having irregular menstruation at age 20 years were at reduced risk for breast cancer mortality (rate ratio = 0.84; 95% confidence interval = 0.74-0.96). The relation was neither confounded nor modified by other breast cancer risk factors.