Coffee consumption and risk of colorectal cancer in the Cancer Prevention Study-II Nutrition Cohort.

BACKGROUND: The association between coffee consumption and colorectal cancer risk generally appears null, but recent evidence suggests that risk may vary by coffee type. We examined associations of caffeinated and decaffeinated coffee intake with colorectal cancer risk overall and with colon and rectum separately, among older U.S. men and women. METHODS: In 1999, 47,010 men and 60,051 women with no previous diagnosis of cancer, aged 47-96 years, in the Cancer Prevention Study-II Nutrition Cohort completed a food frequency questionnaire that assessed caffeinated and decaffeinated coffee intake; consumption was updated in 2003. A total of 1829 colorectal cancer cases were verified through June 2015. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard rate ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking history, alcohol, caffeinated/decaffeinated coffee intake (depending on the model), and other colorectal cancer risk factors. RESULTS: Consumption of ≥2 cups/day of decaffeinated coffee, compared to no decaffeinated coffee, was associated with lower risk of overall colorectal cancer (HR = 0.82, 95% CI: 0.69-0.96, P-trend = 0.04), colon cancer (HR = 0.82, 95% CI: 0.69-0.99, P-trend = 0.05) and rectal cancer (HR = 0.63, 95% CI: 0.40-0.99, P-trend = 0.17). Consumption of ≥2 cups/day of caffeinated coffee was associated with higher risk of rectal cancer (HR = 1.37, 95% CI: 0.99-1.89, P-trend = 0.04), but not with colorectal or colon cancer. CONCLUSION: In this prospective study, higher intake of decaffeinated coffee was associated with lower risk of colorectal, colon, and rectal cancers. Further study on associations of caffeinated and decaffeinated coffee with colorectal cancer risk by subsite is needed.

A blueprint for the primary prevention of cancer: Targeting established, modifiable risk factors.

In the United States, it is estimated that more than 1.7 million people will be diagnosed with cancer, and more than 600,000 will die of the disease in 2018. The financial costs associated with cancer risk factors and cancer care are enormous. To substantially reduce both the number of individuals diagnosed with and dying from cancer and the costs associated with cancer each year in the United States, government and industry and the public health, medical, and scientific communities must work together to develop, invest in, and implement comprehensive cancer control goals and strategies at the national level and expand ongoing initiatives at the state and local levels. This report is the second in a series of articles in this journal that, together, describe trends in cancer rates and the scientific evidence on cancer prevention, early detection, treatment, and survivorship to inform the identification of priorities for a comprehensive cancer control plan. Herein, we focus on existing evidence about established, modifiable risk factors for cancer, including prevalence estimates and the cancer burden due to each risk factor in the United States, and established primary prevention recommendations and interventions to reduce exposure to each risk factor.

Glucosamine use and risk of colorectal cancer: results from the Cancer Prevention Study II Nutrition Cohort.

PURPOSE: Use of glucosamine supplements has been associated with reduced risk of colorectal cancer (CRC) in previous studies; however, information on this association remains limited. METHODS: We examined the association between glucosamine use and CRC risk among 113,067 men and women in the Cancer Prevention Study II Nutrition Cohort. Glucosamine use was first reported in 2001 and updated every 2 years thereafter. Participants were followed from 2001 through June of 2011, during which time 1440 cases of CRC occurred. RESULTS: As has been observed in prior studies, current use of glucosamine, modeled using a time-varying exposure, was associated with lower risk of CRC (HR 0.83; 95% CI 0.71-0.97) compared to never use. However, for reasons that are unclear, this reduction in risk was observed for shorter-duration use (HR 0.68; 95% CI 0.52-0.87 for current users with ≤ 2 years use) rather than longer-duration use (HR 0.90; 95% CI 0.72-1.13 for current users with 3 to < 6 years of use; HR 0.99; 95% CI 0.76-1.29 for current users with ≥ 6 years of use). CONCLUSIONS: Further research is needed to better understand the association between glucosamine use and risk of CRC, and how this association may vary by duration of use.

Associations of Coffee Drinking and Cancer Mortality in the Cancer Prevention Study-II.

Background: Associations of coffee consumption with cancer mortality are inconsistent for many types of cancer, and confounding by smoking is an important concern.Methods: Cox proportional hazards regression was used to estimate multivariable-adjusted HRs for coffee consumption associated with death from all cancers combined and from specific cancer types among 922,896 Cancer Prevention Study-II participants ages 28-94 years who completed a four-page questionnaire and were cancer free at baseline in 1982.Results: During follow-up through 2012, there were 118,738 cancer-related deaths. There was a nonlinear association between coffee consumption and all-cancer death among current smokers and former smokers and no association among never smokers. Among nonsmokers, a 2 cup/day increase in coffee consumption was inversely associated with death from colorectal [HR = 0.97; 95% confidence interval (CI) 0.95-0.99], liver [HR = 0.92; 95% CI, 0.88-0.96], and female breast (HR = 0.97; 95% CI, 0.94-0.99) cancers, and positively associated with esophageal cancer-related death (HR = 1.07; 95% CI, 1.02-1.12). For head and neck cancer, a nonlinear inverse association was observed starting at 2-3 cups per day (HR = 0.72; 95% CI, 0.55-0.95), with similar associations observed at higher levels of consumption.Conclusions: These findings are consistent with many other studies that suggest coffee drinking is associated with a lower risk of colorectal, liver, female breast, and head and neck cancer. The association of coffee consumption with higher risk of esophageal cancer among nonsmokers in our study should be confirmed.Impact: These results underscore the importance of assessing associations between coffee consumption and cancer mortality by smoking status. Cancer Epidemiol Biomarkers Prev; 26(10); 1477-86. ©2017 AACR.

Calcium intake and mortality from all causes, cancer, and cardiovascular disease: the Cancer Prevention Study II Nutrition Cohort.

BACKGROUND: Calcium intake may be important for bone health, but its effects on other outcomes, including cardiovascular disease (CVD) and cancer, remain unclear. Recent reports of adverse cardiovascular effects of supplemental calcium have raised concerns. OBJECTIVE: We investigated associations of supplemental, dietary, and total calcium intakes with all-cause, CVD-specific, and cancer-specific mortality in a large, prospective cohort. DESIGN: A total of 132,823 participants in the Cancer Prevention Study II Nutrition Cohort, who were followed from baseline (1992 or 1993) through 2012 for mortality outcomes, were included in the analysis. Dietary and supplemental calcium information was first collected at baseline and updated in 1999 and 2003. Multivariable-adjusted Cox proportional hazards models with cumulative updating of exposures were used to calculate RRs and 95% CIs for associations between calcium intake and mortality. RESULTS: During a mean follow-up of 17.5 y, 43,186 deaths occurred. For men, supplemental calcium intake was overall not associated with mortality outcomes (P-trend > 0.05 for all), but men who were taking ≥1000 mg supplemental calcium/d had a higher risk of all-cause mortality (RR: 1.17; 95% CI: 1.03, 1.33), which was primarily attributed to borderline statistically significant higher risk of CVD-specific mortality (RR: 1.22; 95% CI: 0.99, 1.51). For women, supplemental calcium was inversely associated with mortality from all causes [RR (95% CI): 0.90 (0.87, 0.94), 0.84 (0.80, 0.88), and 0.93 (0.87, 0.99) for intakes of 0.1 to <500, 500 to <1000, and ≥1000 mg/d, respectively; P-trend < 0.01]. Total calcium intake was inversely associated with mortality in women (P-trend < 0.01) but not in men; dietary calcium was not associated with all-cause mortality in either sex. CONCLUSIONS: In this cohort, associations of calcium intake and mortality varied by sex. For women, total and supplemental calcium intakes are associated with lower mortality, whereas for men, supplemental calcium intake ≥1000 mg/d may be associated with higher all-cause and CVD-specific mortality.

Garlic consumption and colorectal cancer risk in the CPS-II Nutrition Cohort.

PURPOSE: The World Cancer Research Fund/American Institute for Cancer Research identified a probable role for garlic in colorectal cancer prevention based on preclinical evidence and epidemiologic studies, but prospective data are limited. The purpose of this paper was to contribute additional evidence on this topic for men and women in a large prospective cohort study. METHODS: In 1999, 42,824 men and 56,876 women in the Cancer Prevention Study II Nutrition Cohort completed a questionnaire with information on dietary garlic consumption. Garlic supplement use was assessed in 2001. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard rate ratios (HRs) and 95 % confidence intervals (CIs). RESULTS: During 7 years of follow-up, 579 men and 551 women were diagnosed with colorectal cancer. Among men, daily garlic consumption was associated with a non-significant higher colorectal cancer risk (HR = 1.04, 95 % CI 0.99-1.08 for each additional clove or "4 shakes" of garlic per week), whereas the association was borderline inverse in women (HR = 0.95, 95 % CI 0.91-1.00, p heterogeneity by sex = 0.03). Garlic supplement use was not related to a lower risk of colorectal cancer, and in men, former use was associated with a higher risk of colorectal cancer (HR = 1.85, 95 % CI 1.13-3.03). CONCLUSIONS: These results provide weak support for a role of dietary garlic consumption in colorectal cancer prevention in women, but a possible increased risk in men. Further research is needed to confirm different associations by sex.

Impact of diabetes mellitus and insulin use on survival after colorectal cancer diagnosis: the Cancer Prevention Study-II Nutrition Cohort.

PURPOSE: To examine the association between type 2 diabetes mellitus (T2DM) and survival among patients with colorectal cancer (CRC) and to evaluate whether this association varies by sex, insulin treatment, and durations of T2DM and insulin use. PATIENTS AND METHODS: This study was conducted among 2,278 men and women diagnosed with nonmetastatic colon or rectal cancer between 1992 and 2007 in the Cancer Prevention Study-II Nutrition Cohort, a prospective study of cancer incidence. In 1992 to 1993, participants completed a detailed, self-administrated questionnaire. Vital status and cause of death were ascertained through the end of 2008. Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression. RESULTS: Among the 2,278 men and women with nonmetastatic CRC, there were 842 deaths by the end of follow-up (including 377 deaths from CRC and 152 deaths from cardiovascular disease [CVD]). Among men and women combined, compared with patients without T2DM, patients with CRC and T2DM were at higher risk of all-cause mortality (RR, 1.53; 95% CI, 1.28 to 1.83), CRC-specific mortality (RR, 1.29; 95% CI, 0.98 to 1.70), and CVD-specific mortality (RR, 2.16; 95% CI, 1.44 to 3.24), with no apparent differences by sex or durations of T2DM or insulin use. Insulin use, compared with no T2DM, was associated with increased risk of death from all causes (RR, 1.68; 95% CI, 1.22 to 2.31) and CVD (RR, 3.87; 95% CI, 2.12 to 7.08) but not from CRC (RR, 0.58; 95% CI, 0.28 to 1.19). CONCLUSION: Patients with CRC and T2DM have a higher risk of mortality than patients with CRC who do not have T2DM, especially a higher risk of death from CVD.

Coffee, tea, and sugar-sweetened carbonated soft drink intake and pancreatic cancer risk: a pooled analysis of 14 cohort studies.

BACKGROUND: Coffee has been hypothesized to have pro- and anticarcinogenic properties, whereas tea may contain anticarcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, whereas findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. METHODS: In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random-effects model. RESULTS: No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR = 1.10; 95% CI, 0.81-1.48 comparing ≥900 to <0 g/d; 237g ≈ 8oz), tea (MVRR = 0.96; 95% CI, 0.78-1.16 comparing ≥400 to 0 g/d; 237g ≈ 8oz), or SSB (MVRR = 1.19; 95% CI, 0.98-1.46 comparing ≥250 to 0 g/d; 355g ≈ 12oz; P value, test for between-studies heterogeneity > 0.05). These associations were consistent across levels of sex, smoking status, and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR = 1.06; 95% CI, 1.02-1.12). CONCLUSION AND IMPACT: Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.

Folate intake and risk of pancreatic cancer: pooled analysis of prospective cohort studies.

BACKGROUND: Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies. METHODS: We analyzed primary data from 14 prospective cohort studies that included 319,716 men and 542,948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided. RESULTS: During 7-20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, P(trend) = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, P(trend) = .90). No between-study heterogeneity was observed (for dietary folate, P(heterogeneity) = .15; for total folate, P(heterogeneity) = .22). CONCLUSION: Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.

High levels of folate from supplements and fortification are not associated with increased risk of colorectal cancer.

BACKGROUND & AIMS: Folate intake has been inversely associated with colorectal cancer risk in several prospective epidemiologic studies. However, no study fully assessed the influence of the high levels of folate that are frequently consumed in the United States as a result of mandatory folate fortification, which was fully implemented in 1998, and the recent increase in use of folate-containing supplements. There is evidence that consumption of high levels of folic acid, the form of folate used for fortification and in supplements, has different effects on biochemical pathways than natural folates and might promote carcinogenesis. METHODS: We investigated the association between folate intake and colorectal cancer among 43,512 men and 56,011 women in the Cancer Prevention Study II (CPS-II) Nutrition Cohort; 1023 were diagnosed with colorectal cancer between 1999 and 2007, a period entirely after folate fortification began. Cox proportional hazards regression was used to calculate multivariate hazards ratios (RR) and 95% confidence interval (CI). RESULTS: Intake of high levels of natural folate (RRQ5vsQ1=0.86; 95% CI: 0.70-1.06; P trend=.12) or folic acid (RRQ5vsQ1=0.84; 95% CI: 0.68-1.03; P trend=.06) were not significantly associated with risk of colorectal cancer. Total folate intake was significantly associated with lower risk (RRQ5vsQ1=0.81; 95% CI: 0.66-0.99; P trend=.047). CONCLUSIONS: Intake of high levels of total folate reduces risk of colorectal cancer; there is no evidence that dietary fortification or supplementation with this vitamin increases colorectal cancer risk.

Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes.

Risk of colon cancer and coffee, tea, and sugar-sweetened soft drink intake: pooled analysis of prospective cohort studies.

BACKGROUND: The relationships between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk remain unresolved. METHODS: We investigated prospectively the association between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk in a pooled analysis of primary data from 13 cohort studies. Among 731 441 participants followed for up to 6-20 years, 5604 incident colon cancer case patients were identified. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided. RESULTS: Compared with nonconsumers, the pooled multivariable relative risks were 1.07 (95% CI = 0.89 to 1.30, P(trend) = .68) for coffee consumption greater than 1400 g/d (about six 8-oz cups) and 1.28 (95% CI = 1.02 to 1.61, P(trend) = .01) for tea consumption greater than 900 g/d (about four 8-oz cups). For sugar-sweetened carbonated soft drink consumption, the pooled multivariable relative risk comparing consumption greater than 550 g/d (about 18 oz) to nonconsumers was 0.94 (95% CI = 0.66 to 1.32, P(trend) = .91). No statistically significant between-studies heterogeneity was observed for the highest category of each beverage consumed (P > .20). The observed associations did not differ by sex, smoking status, alcohol consumption, body mass index, physical activity, or tumor site (P > .05). CONCLUSIONS: Drinking coffee or sugar-sweetened carbonated soft drinks was not associated with colon cancer risk. However, a modest positive association with higher tea consumption is possible and requires further study.

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.

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.

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.