Dietary intake of omega-6 and omega-3 fatty acids and risk of colorectal cancer in a prospective cohort of U.S. men and women.

BACKGROUND: omega-6 and omega-3 polyunsaturated fatty acids intakes may play opposing roles in inflammation-driven colorectal carcinogenesis. We examined the relationship of these polyunsaturated fatty acids and the ratio of their intake with colorectal cancer risk in a large U.S. prospective cohort. DESIGN: Participants in the Cancer Prevention Study-II Nutrition Cohort completed a detailed questionnaire on diet, medical history, and lifestyle in 1999. Between 1999 and 2005, 869 incident colorectal cancer cases (452 men and 417 women) were identified among 99,080 participants (43,108 men and 55,972 women). Multivariate-adjusted rate ratios were calculated using Cox proportional hazards models. RESULTS: The ratio of total omega-6 to total omega-3 intake was not associated with colorectal cancer risk in either sex. Contrary to our initial hypothesis, total omega-6 intake was inversely related to colorectal cancer risk in men [multivariate relative risk (95% confidence interval) for highest to lowest quartile, 0.81 (0.61-1.07); P(trend) = 0.07], and alpha-linolenic acid, the primary contributor to total omega-3 intake, was associated with increased risk in women for quartiles 2 through 4 versus the lowest quartile [relative risk (95% confidence interval), 1.50 (1.12-2.01), 1.40 (1.04-1.87), and 1.38 (1.02-1.85), respectively; P(trend) = 0.13]. In women, total omega-6 and marine omega-3 intake appeared to be associated with higher and lower risk, respectively, but associations were attenuated with adjustment for other risk factors. CONCLUSIONS: The ratio of omega-6 to omega-3 intake was not related to colorectal cancer risk in this cohort, which may be due to unexpected findings for the individual components. Differential associations by sex warrant further investigation.

Use of blood-pressure-lowering medication and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort.

OBJECTIVES: To examine the association between use of anti-hypertensive drugs and prostate cancer incidence among 48,389 men in the Cancer Prevention Study II Nutrition Cohort. METHODS: Proportional hazards models were used to calculate rate ratios (RR) for use of Beta-Blockers (BBs), Calcium Channel Blockers (CCBs), and ACE Inhibitors (ACE) and incident prostate cancer in time-dependent analyses. RESULTS: During follow-up from 1997 to 2005, we identified 3,031 cases of incident prostate cancer. Anti-hypertensive use was associated with slightly decreased risk of all (RR = 0.90, 95% CI 0.83-0.98) and organ-confined low-grade prostate cancer (RR = 0.89, 95% CI 0.81-0.99), but was not statistically significantly associated with aggressive-fatal prostate cancer (RR = 0.93, 95% CI 0.79-1.10). BB and ACE inhibitor treatment was associated with an approximately 10% lower risk for all prostate cancer in models adjusted for age and race. These associations were attenuated and lost statistical significance when adjusted for history of heart disease. No trend with duration of use was detected. CONCLUSIONS: These results do not support the hypothesis that anti-hypertensive medication is strongly associated with risk of prostate cancer. Confounding by concurrent illness may explain inverse associations seen in other studies.

Postmenopausal hormone therapy and lung cancer risk in the cancer prevention study II nutrition cohort.

BACKGROUND: Studies of postmenopausal hormone therapy and lung cancer incidence have reported positive, negative, and null associations. Most of these studies, however, have had limited ability to control rigorously for cigarette smoking or to examine risk separately by smoking status. METHODS: We examined the association between postmenopausal hormone therapy and lung cancer incidence by smoking status among 72,772 women in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate rate ratios (RR). RESULTS: During follow-up from 1992 to 2003, we identified 659 cases of incident lung cancer. Current use of any postmenopausal hormone therapy was significantly associated with decreased risk of incident lung cancer [multivariate RR, 0.76; 95% confidence interval (95% CI), 0.62-0.92]. Similar risk estimates were observed for unopposed estrogen use (RR, 0.76; 95% CI, 0.60-0.94) and for estrogen plus progestin (RR, 0.76; 95% CI, 0.57-1.01). Risk associated with current use of postmenopausal hormone therapy was decreased among never smokers (RR, 0.56; 95% CI, 0.33-0.95) as well as current smokers (RR, 0.76; 95% CI, 0.55-1.05) and former smokers (RR, 0.76; 95% CI, 0.58-0.99). Former hormone use was not associated with lung cancer. No trend with duration of hormone use was detected. CONCLUSION: These results support the hypothesis that postmenopausal hormone therapy is associated with reduced risk of lung cancer, although the absence of a dose-response relationship weakens the evidence for causality.

Recreational physical activity and risk of Parkinson's disease.

The purpose of this study was to investigate associations between recreational physical activity and Parkinson's disease (PD) risk. We prospectively followed 143,325 participants in the Cancer Prevention Study II Nutrition Cohort from 1992 to 2001 (mean age at baseline = 63). Recreational physical activity was estimated at baseline from the reported number of hours per week on average spent performing light intensity activities (walking, dancing) and moderate to vigorous intensity activities (jogging/running, lap swimming, tennis/racquetball, bicycling/stationary bike, aerobics/calisthenics). Incident cases of PD (n = 413) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, gender, smoking, and other risk factors. Risk of PD declined in the highest categories of baseline recreational activity. The RR comparing the highest category of total recreational activity (men > or = 23 metabolic equivalent task-hours/week [MET-h/wk], women > or = 18.5 MET-h/wk) to no activity was 0.8 (95% CI: 0.6, 1.2; P trend = 0.07). When light activity and moderate to vigorous activity were examined separately, only the latter was found to be associated with PD risk. The RR comparing the highest category of moderate to vigorous activity (men > or = 16 MET-h/wk, women > or = 11.5 MET-h/wk) to the lowest (0 MET-h/wk) was 0.6 (95% CI: 0.4, 1.0; P trend = 0.02). These results did not differ significantly by gender. The results were similar when we excluded cases with symptom onset in the first 4 years of follow-up. Our results may be explained either by a reduction in PD risk through moderate to vigorous activity, or by decreased baseline recreational activity due to preclinical PD.

Genetic variability in iron-related oxidative stress pathways (Nrf2, NQ01, NOS3, and HO-1), iron intake, and risk of postmenopausal breast cancer.

Oxidative stress resulting from excess reactive oxygen species and/or deficiencies in antioxidant capabilities may play a role in breast cancer etiology. In a nested case-control study of postmenopausal women (505 cases and 502 controls) from the American Cancer Society Prevention II Nutrition Cohort, we examined relationships between breast cancer risk and genetic polymorphisms of enzymes involved in the generation and removal of iron-mediated reactive oxygen species. Using unconditional logistic regression, genetic variations in Nrf2 (11108C>T), NQO1 (609C>T), NOS3 (894G>T), and HO-1 [(GT)(n) dinucleotide length polymorphism] were not associated with breast cancer risk in a multivariate model. A significant dose trend (P trend = 0.04), however, was observed for total number of putative "at-risk" alleles (Nrf T, NQO1 T, NOS T, and HO-1 LL and LM genotypes), with those carrying three or more at-risk alleles having an odds ratio (OR) of 1.56 [95% confidence interval (95% CI), 0.97-2.51] compared with those having none. When examined in relation to iron, carriage of three or more high-risk alleles in the highest tertile of iron intake (OR, 2.27; 95% CI, 0.97-5.29; P trend = 0.02; P interaction = 0.30) or among users of supplemental iron (OR, 2.39; 95% CI, 1.09-5.26; P trend = 0.02; P interaction = 0.11) resulted in a greater than 2-fold increased risk compared with women with no high-risk alleles. Increased risk was also observed among supplement users with the HO-1 LL or LM genotypes (OR, 1.56; 95% CI, 1.01-2.41; P interaction = 0.32) compared with S allele carriers and MM genotypes combined. These results indicate that women with genotypes resulting in potentially higher levels of iron-generated oxidative stress may be at increased risk of breast cancer and that this association may be most relevant among women with high iron intake.

Dairy, calcium, and vitamin D intake and postmenopausal breast cancer risk in the Cancer Prevention Study II Nutrition Cohort.

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 < or =500 mg/d [RR, 0.80; 95% confidence interval (95% CI), 0.67-0.95; P(trend) = 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; P(trend) = 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; P(trend) = 0.004); dairy products (RR, 0.73; 95% CI, 0.57-0.93; P(trend) = 0.0003), and dietary vitamin D (RR, 0.74; 95% CI, 0.59-0.93; P(trend) = 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.

Use of multivitamins and prostate cancer mortality in a large cohort of US men.

OBJECTIVE: To assess the association between the use of multivitamins and prostate cancer mortality. METHODS: A total of 5585 deaths from prostate cancer were identified during 18 years of follow-up of 475,726 men who were cancer-free and provided complete information on multivitamin use at enrollment in the Cancer Prevention Study II (CPS-II) cohort in 1982. Cox proportional hazards modeling was used to measure the association between multivitamin use at baseline and death from prostate cancer and to adjust for potential confounders. RESULTS: The death rate from prostate cancer was marginally higher among men who took multivitamins regularly (> or =15 times/month) compared to non-users (multivariate rate ratio=1.07, 95% CI: 0.99-1.15); this risk was statistically significant only for those multivitamin users who used no additional (vitamin A, C, or E) supplements (multivariate rate ratio=1.15, 95% CI: 1.05-1.26). In addition, risk was greatest during the initial four years of follow-up (1982-1986, multivariate rate ratio=1.12, 95 CI: 0.87-1.46). CONCLUSIONS: Regular multivitamin use was associated with a small increase in prostate cancer death rates in our study, and this association was limited to a subgroup of users.

Vitamin E intake and risk of amyotrophic lateral sclerosis.

Oxidative stress may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). We therefore examined prospectively whether individuals who regularly use supplements of the antioxidant vitamins E and C have a lower risk of ALS than nonusers. The study population comprised 957,740 individuals 30 years of age or older participating in the American Cancer Society's Cancer Prevention Study II. Information on vitamin use was collected at time of recruitment in 1982; participants then were followed up for ALS deaths from 1989 through 1998 via linkage with the National Death Index. During the follow-up, we documented 525 deaths from ALS. Regular use of vitamin E supplements was associated with a lower risk of dying of ALS. The age- and smoking-adjusted relative risk was 0.99 (95% confidence interval [CI], 0.69-1.41) among occasional users, 0.59 (95% CI, 0.36-0.96) in regular users for less than 10 years, and 0.38 (95% CI, 0.16-0.92) in regular users for 10 years or more as compared with nonusers of vitamin E (p for trend = 0.004). In contrast, no significant associations were found for use of vitamin C or multivitamins. These results suggest that vitamin E supplementation could have a role in ALS prevention.

Coffee consumption, gender, and Parkinson's disease mortality in the cancer prevention study II cohort: the modifying effects of estrogen.

Caffeine consumption is associated with a reduced risk of Parkinson's disease in men but not in women. This gender difference may be due to an interaction between caffeine and use of postmenopausal estrogens. The authors prospectively assessed the relation between coffee consumption and Parkinson's disease mortality among participants in the Cancer Prevention Study II, a cohort of over 1 million people enrolled in 1982. Causes of deaths were ascertained through death certificates from January 1, 1989, through 1998. Parkinson's disease was listed as a cause of death in 909 men and 340 women. After adjustment for age, smoking, and alcohol intake, coffee consumption was inversely associated with Parkinson's disease mortality in men (p(trend) = 0.01) but not in women (p = 0.6). In women, this association was dependent on postmenopausal estrogen use; the relative risk for women drinking 4 or more cups (600 ml) of coffee per day compared with nondrinkers was 0.47 (95% confidence interval: 0.27, 0.80; p = 0.006) among never users and 1.31 (95% confidence interval: 0.75, 2.30; p = 0.34) among users. These results suggest that caffeine reduces the risk of Parkinson's disease but that this hypothetical beneficial effect may be prevented by use of estrogen replacement therapy.

Vitamin E supplements and risk of prostate cancer in U.S. men.

Supplementation with alpha-tocopherol (a form of vitamin E) was associated with decreased risk of prostate cancer in a randomized trial among Finnish smokers. We examined the association between vitamin E supplement use and prostate cancer incidence in the Cancer Prevention Study II Nutrition Cohort. Participants in the study completed a detailed questionnaire at enrollment in 1992-1993. Historical information was also available from a questionnaire completed in 1982 at enrollment in a previous cohort. Through August 31, 1999, we documented 4,281 cases of incident prostate cancer among 72,704 men. Multivariate-adjusted rate ratios (RRs) were calculated using Cox Proportional Hazards models. Regular vitamin E supplement use (>/=4 times per week) was not associated with overall risk of prostate cancer or with risk of advanced prostate cancer at diagnosis. No trend was seen with increasing dose of vitamin E. Men who reported regular vitamin E use in both 1982 and in 1992-1993 were not at lower risk of prostate cancer. Among current smokers, there was a suggestion of slightly reduced risk with regular vitamin E supplement use [RR = 0.87, 95% confidence interval (CI) = 0.67-1.11]. Our results do not support an important role for vitamin E supplements in prostate cancer prevention.

Multivitamin use and colorectal cancer incidence in a US cohort: does timing matter?

Multivitamins contain several nutrients, including folic acid, that are hypothesized to reduce the risk of colorectal cancer. Previous studies suggest that multivitamin use may reduce colorectal cancer risk but only after a long latency period. The authors examined the association between regular multivitamin use (four or more times per week) and colorectal cancer incidence among 145,260 men and women in the Cancer Prevention Study II Nutrition Cohort. Current multivitamin use was reported on a questionnaire at enrollment in 1992-1993. All participants had also reported multivitamin use on a questionnaire completed for a different study approximately 10 years earlier (in 1982). The authors observed 797 incident cases of colorectal cancer during follow-up from 1992 to 1997. After multivariate adjustment, regular multivitamin use at enrollment was not associated with risk of colorectal cancer (rate ratio = 1.04, 95% confidence interval: 0.87, 1.23), whereas regular multivitamin use 10 years before enrollment was associated with reduced risk (rate ratio = 0.71, 95% confidence interval: 0.57, 0.89). Regular multivitamin users 10 years before enrollment were at similarly reduced risk whether they were still regular multivitamin users at enrollment or had stopped. These results are consistent with the hypothesis that past, but not recent, multivitamin use may be associated with modestly reduced risk of colorectal cancer.

Calcium, dairy products, and risk of prostate cancer in a prospective cohort of United States men.

Intake of calcium and/or dairy products has been associated with increased risk of prostate cancer in some epidemiological studies. One potential biological mechanism is that high calcium intake down-regulates 1,25 dihydroxy vitamin D(3), which may increase cell proliferation in the prostate. We examined the association between calcium, dairy intake, and prostate cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a prospective cohort of elderly United States adults. Participants in the study completed a detailed questionnaire on diet, medical history, and lifestyle at enrollment in 1992-1993. After excluding men with a history of cancer or incomplete dietary information, 65,321 men remained for analysis. During follow-up through August 31, 1999, we documented 3811 cases of incident prostate cancer. Multivariate-adjusted rate ratios (RRs) were calculated using Cox proportional hazards models. Total calcium intake (from diet and supplements) was associated with modestly increased risk of prostate cancer [RR = 1.2, 95% confidence interval (CI) = 1.0-1.6 for >or=2000 versus <700 mg/day, P trend = 0.02). High dietary calcium intake (>or=2000 versus <700 mg/day) was also associated with increased risk of prostate cancer (RR = 1.6, 95% CI = 1.1-2.3, P trend = 0.10), although moderate levels of dietary calcium were not associated with increased risk. Dairy intake was not associated with prostate cancer risk. The association between prostate cancer and total calcium intake was strongest for men who reported not having prostate-specific antigen testing before 1992 (RR = 1.5, 95% CI = 1.1-2.0, P trend < 0.01 for >or= 2000 mg/day of total calcium; RR = 2.1, 95% CI = 1.3-3.4 >or=2000 mg/day of dietary calcium, P trend = 0.04). Our results support the hypothesis that very high calcium intake, above the recommended intake for men, may modestly increase risk of prostate cancer.

Calcium, vitamin D, dairy products, and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States).

OBJECTIVE: Calcium, vitamin D, and dairy product intake may reduce the risk of colorectal cancer. We therefore examined the association between these factors and risk of colorectal cancer in a large prospective cohort of United States men and women. METHODS: Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed questionnaire on diet, medical history, and lifestyle in 1992-93. After excluding participants with a history of cancer or incomplete dietary information, 60,866 men and 66,883 women remained for analysis. During follow-up through 31 August 1997 we documented 421 and 262 cases of incident colorectal cancers among men and women, respectively. Multivariate-adjusted rate ratios (RR) were calculated using Cox proportional hazards models. RESULTS: Total calcium intake (from diet and supplements) was associated with marginally lower colorectal cancer risk in men and women (RR = 0.87, 95% CI 0.67-1.12, highest vs lowest quintiles, p trend = 0.02). The association was strongest for calcium from supplements (RR = 0.69, 95% CI 0.49-0.96 for > or = 500 mg/day vs none). Total vitamin D intake (from diet and multivitamins) was also inversely associated with risk of colorectal cancer, particularly among men (RR = 0.71, 95% CI 0.51-0.98, p trend = 0.02). Dairy product intake was not related to overall risk. CONCLUSIONS: Our results support the hypothesis that calcium modestly reduces risk of colorectal cancer. Vitamin D was associated with reduced risk of colorectal cancer only in men.

Vitamin C and vitamin E supplement use and bladder cancer mortality in a large cohort of US men and women.

Some epidemiologic studies suggest that use of vitamin C or vitamin E supplements, both potent antioxidants, may reduce the risk of bladder cancer. The authors examined the association between use of individual vitamin C and vitamin E supplements and bladder cancer mortality among 991,522 US adults in the Cancer Prevention Study II (CPS-II) cohort. CPS-II participants completed a self-administered questionnaire at enrollment in 1982 and were followed regarding mortality through 1998. During follow-up, 1,289 bladder cancer deaths occurred (962 in men and 327 in women). Rate ratios were adjusted for age, sex, cigarette smoking, education, and consumption of citrus fruits and vegetables. Regular vitamin C supplement use (>or=15 times per month) was not associated with bladder cancer mortality, regardless of duration (rate ratio (RR) = 0.91, 95% confidence interval (CI): 0.68, 1.20 for <10 years' use; RR = 1.25, 95% CI: 0.91, 1.72 for >or=10 years' use). Regular vitamin E supplement use for >or=10 years was associated with a reduced risk of bladder cancer mortality (RR = 0.60, 95% CI: 0.37, 0.96), but regular use of shorter duration was not (RR = 1.04, 95% CI: 0.77, 1.40). Results support the hypothesis that long-duration vitamin E supplement use may reduce the risk of bladder cancer mortality.

The American Cancer Society Cancer Prevention Study II Nutrition Cohort: rationale, study design, and baseline characteristics.

BACKGROUND: Large-scale, prospective cohort studies have played a critical role in discovering factors that contribute to variability in cancer risk in human populations. Epidemiologists and volunteers at the American Cancer Society (ACS) were among the first to establish such cohorts, beginning in the early 1950s and continuing through the present, and these ACS cohorts have made landmark contributions in many areas of epidemiologic research. METHODS AND RESULTS: The Cancer Prevention Study II Nutrition Cohort was established in 1992 and was designed to investigate the relation between diet and other lifestyle factors and exposures and the risk of cancer, mortality, and survival. The cohort includes over 84,000 men and 97,000 women who completed a mailed questionnaire in 1992. New questionnaires are sent to surviving cohort members every other year to update exposure information and to ascertain new occurrences of cancer; a 90% response rate was achieved for follow-up questionnaires in 1997 and 1999. Reported cancers are verified through medical records, registry linkage, or death certificates. The cohort is followed actively for all cases of incident cancer and for all causes of death. Through a collaborative effort among ACS national and division staff, volunteers, and the American College of Surgeons, blood samples were collected from a subgroup of 40,000 cohort members and are in storage at a central repository for future investigation of dietary, hormonal, genetic, and other factors and cancer risk. Collection of DNA samples from buccal cells in an additional 50,000 cohort members is underway currently and will be completed in 2002. CONCLUSIONS: This new cohort of both men and women promises to be particularly valuable for the study of cancer occurrence, mortality, and survival as they relate to obesity and weight change, physical activity at various points in life, vitamin supplement use, exogenous hormone use, other medications (such as aspirin and nonsteroidal anti- inflammatory drugs) and cancer screening modalities.

The American Cancer Society Cancer Prevention Study II Nutrition Cohort: rationale, study design, and baseline characteristics.

BACKGROUND: Large-scale, prospective cohort studies have played a critical role in discovering factors that contribute to variability in cancer risk in human populations. Epidemiologists and volunteers at the American Cancer Society (ACS) were among the first to establish such cohorts, beginning in the early 1950s and continuing through the present, and these ACS cohorts have made landmark contributions in many areas of epidemiologic research. METHODS AND RESULTS: The Cancer Prevention Study II Nutrition Cohort was established in 1992 and was designed to investigate the relation between diet and other lifestyle factors and exposures and the risk of cancer, mortality, and survival. The cohort includes over 84,000 men and 97,000 women who completed a mailed questionnaire in 1992. New questionnaires are sent to surviving cohort members every other year to update exposure information and to ascertain new occurrences of cancer; a 90% response rate was achieved for follow-up questionnaires in 1997 and 1999. Reported cancers are verified through medical records, registry linkage, or death certificates. The cohort is followed actively for all cases of incident cancer and for all causes of death. Through a collaborative effort among ACS national and division staff, volunteers, and the American College of Surgeons, blood samples were collected from a subgroup of 40,000 cohort members and are in storage at a central repository for future investigation of dietary, hormonal, genetic, and other factors and cancer risk. Collection of DNA samples from buccal cells in an additional 50,000 cohort members is underway currently and will be completed in 2002. CONCLUSIONS: This new cohort of both men and women promises to be particularly valuable for the study of cancer occurrence, mortality, and survival as they relate to obesity and weight change, physical activity at various points in life, vitamin supplement use, exogenous hormone use, other medications (such as aspirin and nonsteroidal anti-inflammatory drugs) and cancer screening modalities.

Vitamin C, vitamin E, and multivitamin supplement use and stomach cancer mortality in the Cancer Prevention Study II cohort.

Supplementation with antioxidant vitamins has been associated with decreased risk of stomach cancer or regression of precancerous lesions in high-risk areas of China and Colombia. We examined the association between stomach cancer mortality and regular use (> or =15 times per month) of individual vitamin C supplements, individual vitamin E supplements, and multivitamins among 1,045,923 United States adults in the Cancer Prevention Study II (CPS-II) cohort. CPS-II participants completed a questionnaire at enrollment in 1982 and were followed for mortality through 1998. During follow-up, there were 1,725 stomach cancer deaths (1,127 in men and 598 in women). After adjustment for multiple potential stomach cancer risk factors, vitamin C use at enrollment was associated with reduced risk of stomach cancer mortality [rate ratio (RR), 0.83; 95% confidence interval (CI), 0.68-1.01]. However, this reduction in risk was observed only among participants with short duration use at enrollment (RR, 0.68; 95% CI, 0.51-0.91 for <10 years of use; RR, 1.00; 95% CI, 0.73-1.38 for > or =10 years of use). There was no association between stomach cancer mortality and regular use of vitamin E (RR, 1.02; 95% CI, 0.82-1.27) or multivitamins (RR, 0.89; 95% CI, 0.77-1.03), regardless of duration of use. Our results suggest that the use of vitamin C, vitamin E, or multivitamin supplements may not substantially reduce risk of stomach cancer mortality in North American populations in which stomach cancer rates are relatively low. Our results do not rule out effects of vitamin supplementation in areas in which stomach cancer rates are high and stomach cancer etiology may differ.