Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women.

Within the two Nurses' Health Study cohorts of US women, we examined whether higher intakes of vitamin C, vitamin E, retinol, or individual tocopherols or carotenoids are associated with a lower risk of melanoma. We confirmed 414 cases of invasive melanoma among over 162,000 Caucasian women aged 25-77 years during more than 1.6 million person-years of follow-up. Diet was measured every 4 years with a food frequency questionnaire and supplement use was reported every 2 years. Several measures of sun sensitivity were assessed and included in proportional hazards models. We found that vitamins A, C, E and their individual components were not associated with a lower risk of melanoma. Only retinol intake from foods plus supplements appeared protective within a subgroup of women who were otherwise at low risk based on nondietary factors (relative risk (RR)=0.39, 95% confidence interval (CI) 0.22-0.71 for >/=1,800 vs 400 microg day(-1), P for linear trend=0.01). Contrary to expectation, we observed higher risks of melanoma with greater intakes of vitamin C from food only (RR=1.43, 95% CI 1.01-2.00 for >/=175 vs <90 mg day(-1), P for linear trend=0.05) and a significant positive dose-response with frequency of orange juice consumption (P=0.008). Further research is needed to determine whether another component in foods such as orange juice may contribute to an increase in risk.

Caffeine, postmenopausal estrogen, and risk of Parkinson's disease.

BACKGROUND: Men who regularly consume caffeinated drinks have a lower risk of PD than do nondrinkers, but this relation has not been found in women. Because this sex difference could be due to hormonal effects, the authors examined prospectively the risk of PD according to use of postmenopausal hormones and caffeine intake among participants in the Nurses' Health Study. METHODS: The study population comprised 77,713 women free of PD, stroke, or cancer at baseline, who were postmenopausal at baseline or reached menopause before the end of the study. During 18 years of follow-up the authors documented 154 cases of PD. RESULTS: Overall, the risk of PD was similar in women using hormones and women who never used hormones (relative risk 1.02, 95% CI 0.69 to 1.52). Use of hormones, however, was associated with a reduced risk of PD among women with low caffeine consumption (RR 0.39, 95% CI 0.13 to 1.17), and with increased risk among women with high caffeine consumption (RR 2.44, 95% CI 0.75 to 7.86; p for interaction = 0.01). Among hormone users, women consuming six or more cups of coffee per day had a fourfold higher risk of PD (RR 3.92, 95% CI 1.49 to 10.34; p = 0.006) than did women who never drink coffee. CONCLUSION: These results suggest that caffeine reduces the risk of PD among women who do not use postmenopausal hormones, but increases risk among hormone users. Clinical trials of caffeine or estrogens in women should avoid the combined use of these agents.

Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis.

BACKGROUND: Antioxidant vitamins may decrease risk of cancer by limiting oxidative DNA damage leading to cancer initiation. Few prospective studies have assessed relations between antioxidant vitamins and ovarian carcinoma. METHODS: The authors prospectively assessed consumption of vitamins A, C, and E and specific carotenoids, as well as fruit and vegetable intake, in relation to ovarian carcinoma risk among 80,326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin carcinoma. Women reported on known and suspected ovarian carcinoma risk factors including reproductive factors, smoking, and use of vitamin supplements on biennial mailed questionnaires from 1976 to 1996. Food frequency questionnaires were included in 1980, 1984, 1986, and 1990. The authors confirmed 301 incident cases of invasive epithelial ovarian carcinoma during 16 years of dietary follow-up (1980-1996). Pooled logistic regression was used to control for age, oral contraceptive use, body mass index, smoking history, parity, and tubal ligation. RESULTS: The authors observed no association between ovarian carcinoma risk and antioxidant vitamin consumption from foods, or foods and supplements together. The multivariate relative risks (95% confidence intervals [CIs]) for ovarian carcinoma among women in the highest versus lowest quintile of intake were 1.04 (95% CI, 0.72-1.51) for vitamin A from foods and supplements; 1.01 (95% CI, 0.69-1.47) for vitamin C; 0.88 (95% CI, 0.61-1.27) for vitamin E; and 1.10 (95% CI, 0.76-1.59) for beta-carotene. Among users of vitamin supplements, the authors found no evidence of an association between dose or duration of any specific vitamin and ovarian carcinoma risk, although the authors had limited power to assess these relations. No specific fruits or vegetables were associated significantly with ovarian carcinoma risk. The authors found no association between ovarian carcinoma and consumption of total fruits or vegetables, or specific subgroups including cruciferous vegetables, green leafy vegetables, legumes, or citrus fruits. Women who consumed at least 2.5 total servings of fruits and vegetables as adolescents had a 46% reduction in ovarian carcinoma risk (relative risk, 0.54, 95% CI, 0.29-1.03; P value for trend 0.04). CONCLUSIONS: These data do not support an important relation between consumption of antioxidant vitamins from foods or supplements, or intake of fruits and vegetables, and incidence of ovarian carcinoma in this cohort. However, modest associations cannot be excluded, and the authors' finding of an inverse association for total fruit and vegetable intake during adolescence raises the possibility that the pertinent exposure period may be much earlier than formerly anticipated.

Cross-sectional measurement of nutrient intake among adolescents in 1996.

BACKGROUND: Many components are involved in an assessment of diet and health among youth. To address these issues and document the major contributions of fat, fiber, vitamins, and minerals to the diet, we analyzed baseline cross-sectional data from a cohort of 16,882 youth. METHODS: Cross-sectional analyses were conducted on the Growing Up Today Study dietary data reported by 16,882 9- to 14-year-olds in 1996. The adolescent food frequency questionnaire was used to assess this age group's eating habits. Arithmetic means and standard deviations were calculated on energy-adjusted and unadjusted data. RESULTS: Mean intake (including vitamin/mineral supplementation) for all nutrients met 100% of the RDAs, except calcium for girls. Comparing the servings of foods with the USDA Food Pyramid, neither boys nor girls met recommended number of servings except for dairy. Overweight participants consumed fewer kilocalories and lower levels of nutrients than their nonoverweight peers. CONCLUSION: These cross-sectional data from 1996 indicate that this cohort is consuming foods and nutrients comparable with national data of less fat and more carbohydrates in their diet. Overweight participants have similar dietary patterns except for total energy. The cohort's diet (with vitamin/mineral supplementation) is meeting the RDAs, but actual foods consumed suggest a lack of balance in the diet.

Prospective study of caffeine consumption and risk of Parkinson's disease in men and women.

Results of case-control studies and of a prospective investigation in men suggest that consumption of coffee could protect against the risk of Parkinson's disease, but the active constituent is not clear. To address the hypothesis that caffeine is protective against Parkinson's disease, we examined the relationship of coffee and caffeine consumption to the risk of this disease among participants in two ongoing cohorts, the Health Professionals' Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). The study population comprised 47,351 men and 88,565 women who were free of Parkinson's disease, stroke, or cancer at baseline. A comprehensive life style and dietary questionnaire was completed by the participants at baseline and updated every two to four years. During the follow-up (10 years in men, 16 years in women), we documented a total of 288 incident cases of Parkinson's disease. Among men, after adjustment for age and smoking, the relative risk of Parkinson's disease was 0.42 (95% CI: 0.23-0.78; p for trend < 0.001) for men in the top one-fifth of caffeine intake compared to those in the bottom one-fifth. An inverse association was also observed with consumption of coffee (p for trend = 0.004), caffeine from noncoffee sources (p for trend < 0.001), and tea (p for trend = 0.02) but not decaffeinated coffee. Among women, the relationship between caffeine or coffee intake and risk of Parkinson's disease was U-shaped, with the lowest risk observed at moderate intakes (1-3 cups of coffee/day, or the third quintile of caffeine consumption). These results support a possible protective effect of moderate doses of caffeine on risk of Parkinson's disease.

Vitamin supplement use and the risk of non-Hodgkin's lymphoma among women and men.

The authors examined use of individual supplements of vitamins A, C, and E only and multivitamins in relation to risk of non-Hodgkin's lymphoma in prospective cohorts of 88,410 women in the Nurses' Health Study (1980-1996), with 261 incident cases during 16 years of follow-up, and of 47,336 men in the Health Professionals Follow-Up Study (1986-1996), with 111 incident cases during 10 years of follow-up. Multivitamin use was associated with a higher risk of non-Hodgkin's lymphoma among women but not among men; the multivariate relative risks for long-term duration (10 or more years) were 1.48 (95% confidence interval (CI): 1.01, 2.16) for women and 0.85 (95% CI: 0.45, 1.58) for men. The pooled multivariate relative risk from the two cohorts was 1.18 (95% CI: 0.70, 2.02). Use of individual supplements of vitamins A, C, and E only was not associated with risk among men. An increased risk associated with the use of individual supplements of vitamins A, C, and E only among women appeared to be secondary to the use of multivitamins by the same persons. Because an elevated risk among multivitamin users was not observed consistently in the two cohorts and the pooled data were not significant, the elevated risk among women may be the result of chance.

Coffee and alcohol consumption and the risk of pancreatic cancer in two prospective United States cohorts.

Although most prospective cohort studies do not support an association between coffee consumption and pancreatic cancer, the findings for alcohol are inconsistent. Recently, a large prospective cohort study of women reported statistically significant elevations in risk of pancreatic cancer for both coffee and alcoholic beverage consumption. We obtained data on coffee, alcohol, and other dietary factors using semiquantitative food frequency questionnaires administered at baseline (1986 in the Health Professionals Follow-Up Study and 1980 in the Nurses' Health Study) and in subsequent follow-up questionnaires. Data on other risk factors for pancreatic cancer, including cigarette smoking, were also available. Individuals with a history of cancer at study initiation were excluded from all of the analyses. During the 1,907,222 person-years of follow-up, 288 incident cases of pancreatic cancer were diagnosed. The data were analyzed separately for each cohort, and results were pooled to compute overall relative risks (RR). Neither coffee nor alcohol intakes were associated with an increased risk of pancreatic cancer in either cohort or after pooling the results (pooled RR, 0.62; 95% confidence interval, 0.27-1.43, for >3 cups of coffee/day versus none; and pooled RR, 1.00; 95% confidence interval, 0.57-1.76, for > or = 30 grams of alcohol/day versus none). The associations did not change with analyses examining different latency periods for coffee and alcohol. Similarly, no statistically significant associations were observed for intakes of tea, decaffeinated coffee, total caffeine, or alcoholic beverages. Data from these two large cohorts do not support any overall association between coffee intake or alcohol intake and risk of pancreatic cancer.

Intake of fish and omega-3 fatty acids and risk of stroke in women.

CONTEXT: Some prospective studies have shown an inverse association between fish intake and risk of stroke, but none has examined the relationship of fish and omega-3 polyunsaturated fatty acid intake with risk of specific stroke subtypes. OBJECTIVE: To examine the association between fish and omega-3 polyunsaturated fatty acid intake and risk of stroke subtypes in women. DESIGN, SETTING, AND SUBJECTS: Prospective cohort study of women in the Nurses' Health Study cohort, aged 34 to 59 years in 1980, who were free from prior diagnosed cardiovascular disease, cancer, and history of diabetes and hypercholesterolemia and who completed a food frequency questionnaire including consumption of fish and other frequently eaten foods. The 79 839 women who met our eligibility criteria were followed up for 14 years. MAIN OUTCOME MEASURE: Relative risk of stroke in 1980-1994 compared by category of fish intake and quintile of omega-3 polyunsaturated fatty acid intake. RESULTS: After 1 086 261 person-years of follow-up, 574 incident strokes were documented, including 119 subarachnoid hemorrhages, 62 intraparenchymal hemorrhages, 303 ischemic strokes (264 thrombotic and 39 embolic infarctions), and 90 strokes of undetermined type. Among thrombotic infarctions, 90 large-artery occlusive infarctions and 142 lacunar infarctions were identified. Compared with women who ate fish less than once per month, those with higher intake of fish had a lower risk of total stroke: the multivariate relative risks (RRs), adjusted for age, smoking, and other cardiovascular risk factors, were 0.93 (95% confidence interval [CI], 0.65-1.34) for fish consumption 1 to 3 times per month, 0.78 (95% CI, 0.55-1.12) for once per week, 0.73 (95% CI, 0.47-1.14) for 2 to 4 times per week, and 0.48 (95% CI, 0.21-1.06) for 5 or more times per week (P for trend =.06). Among stroke subtypes, a significantly reduced risk of thrombotic infarction was found among women who ate fish 2 or more times per week (multivariate RR, 0.49; 95% CI, 0.26-0.93). Women in the highest quintile of intake of long-chain omega-3 polyunsaturated fatty acids had reduced risk of total stroke and thrombotic infarction, with multivariate RRs of 0.72 (95% CI, 0.53-0.99) and 0.67 (95% CI, 0.42-1.07), respectively. When stratified by aspirin use, fish and omega-3 polyunsaturated fatty acid intakes were inversely associated with risk of thrombotic infarction, primarily among women who did not regularly take aspirin. There was no association between fish or omega-3 polyunsaturated fatty acid intake and risk of hemorrhagic stroke. CONCLUSIONS: Our data indicate that higher consumption of fish and omega-3 polyunsaturated fatty acids is associated with a reduced risk of thrombotic infarction, primarily among women who do not take aspirin regularly, but is not related to risk of hemorrhagic stroke.

Physical activity and risk for cardiovascular events in diabetic women.

BACKGROUND: Increased physical activity has been associated with reduced risk for cardiovascular disease in the general population, but data are limited on its role among persons with type 2 diabetes mellitus. OBJECTIVE: To determine whether physical activity decreases risk for cardiovascular disease among diabetic women. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study. PATIENTS: 5125 female nurses with diabetes. MEASUREMENTS: Physical activity was first assessed in 1980 and was updated in 1982, 1986, 1988, and 1992 through validated questionnaires. Average hours of moderate or vigorous exercise and a metabolic equivalent of task (MET) score were computed. RESULTS: During 14 years of follow-up (31 432 person-years), 323 new cases of cardiovascular disease were documented (225 cases of coronary heart disease and 98 cases of stroke). The age-adjusted relative risks according to average hours of moderate or vigorous activity per week (<1, 1 to 1.9, 2 to 3.9, 4 to 6.9, >/=7) were 1.0, 0.93 (95% CI, 0.69 to 1.26), 0.82 (CI, 0.61 to 1.10), 0.54 (CI, 0.39 to 0.76), and 0.52 (CI, 0.25 to 1.09) (P < 0.001 for trend). These figures did not change materially after adjustment for smoking, body mass index, and other cardiovascular risk factors (1.0, 1.02, 0.87, 0.61, and 0.55, respectively; P = 0.001 for trend). In separate analyses, levels of physical activity were inversely associated with coronary heart disease and ischemic stroke. Among women who did not exercise vigorously, the multivariate relative risks for cardiovascular disease across quartiles of MET score for walking were 1.0, 0.85, 0.63, and 0.56 (P = 0.03 for trend). Faster usual walking pace was independently associated with lower risk. CONCLUSION: Among diabetic women, increased physical activity, including regular walking, is associated with substantially reduced risk for cardiovascular events.

Prospective study of fat and protein intake and risk of intraparenchymal hemorrhage in women.

BACKGROUND: -Dietary animal fat and protein have been inversely associated with a risk of intraparenchymal hemorrhage in ecological studies. METHODS AND RESULTS: In 1980, 85 764 women in the Nurses' Health Study cohort, who were 34 to 59 years old and free of diagnosed cardiovascular disease and cancer, completed dietary questionnaires. From these questionnaires, we calculated fat and protein intake. By 1994, after 1.16 million person-years of follow-up, 690 incident strokes, including 74 intraparenchymal hemorrhages, had been documented. Multivariate-adjusted risk of intraparenchymal hemorrhage was higher among women in the lowest quintile of energy-adjusted saturated fat intake than at all higher levels of intake (relative risk [RR], 2.36; 95% CI, 1.10 to 5.09; P:=0.03). For trans unsaturated fat, the corresponding RR was 2.50 (95% CI, 1.35 to 4.65; P:=0.004). Animal protein intake was inversely associated with risk (RR in the highest versus lowest quintiles, 0.32; 95% CI, 0.10 to 1.00; P:=0.04). The excess risk associated with low saturated fat intake was observed primarily among women with a history of hypertension (RR, 3.66; 95% CI, 1.09 to 12.3; P=0.04), but such an interaction was not seen for trans unsaturated fat or animal protein. These nutrients were not related to risk of other stroke subtypes. Dietary cholesterol and monounsaturated and polyunsaturated fat were not related to risk of any stroke subtype. CONCLUSIONS: Low intake of saturated fat and animal protein was associated with an increased risk of intraparenchymal hemorrhage, which may help to explain the high rate of this stroke subtype in Asian countries. The increased risk with low intake of saturated fat and trans unsaturated fat is compatible with the reported association between low serum total cholesterol and risk.

Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers.

BACKGROUND: Frequent consumption of fruit and vegetables has been associated with a reduced risk of colorectal cancer in many observational studies. METHODS: We prospectively investigated the association between fruit and vegetable consumption and the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (88 764 women) and the Health Professionals' Follow-up Study (47 325 men). Diet was assessed and cumulatively updated in 1980, 1984, 1986, and 1990 among women and in 1986 and 1990 among men. The incidence of cancer of the colon and rectum was ascertained up to June or January of 1996, respectively. Relative risk (RR) estimates were calculated with the use of pooled logistic regression models accounting for various potential confounders. All statistical tests were two-sided. RESULTS: With a follow-up including 1 743 645 person-years and 937 cases of colon cancer, we found little association of colon cancer incidence with fruit and vegetable consumption. For women and men combined, a difference in fruit and vegetable consumption of one additional serving per day was associated with a covariate-adjusted RR of 1.02 (95% confidence interval [CI] = 0.98-1.05). A difference in vegetable consumption of one additional serving per day was associated with an RR of 1.03 (95% CI = 0.97-1.09). Similar results were obtained for women and men considered separately. A difference in fruit consumption of one additional serving per day was associated with a covariate-adjusted RR for colon cancer of 0.96 (95% CI = 0.89-1.03) among women and 1. 08 (95% CI = 1.00-1.16) among men. For rectal cancer (total, 244 cases), a difference in fruit and vegetable consumption of one additional serving per day was associated with an RR of 1.02 (95% CI = 0.95-1.09) in men and women combined. None of these associations was modified by vitamin supplement use or smoking habits. CONCLUSIONS: Although fruits and vegetables may confer protection against some chronic diseases, their frequent consumption does not appear to confer protection from colon or rectal cancer.

Proportion of colon cancer risk that might be preventable in a cohort of middle-aged US men.

OBJECTIVE: Diet and lifestyle likely play major roles in colon cancer incidence; however, the proportion of colon cancer risk that might be preventable is unknown. Thus, we estimated the proportion of colon cancer risk among men in the prospective Health Professionals Follow-up Study that might be attributable to a constellation of modifiable risk factors, and thus might be preventable. METHODS: We included 47,927 men aged 40-75 years in 1986, among whom we confirmed 411 colon cancer cases from 1986 to 1996. Risk factors considered were obesity, physical inactivity, alcohol consumption, early adulthood cigarette smoking, red meat consumption, and low intake of folic acid from supplements. We calculated a risk score that was the sum across the six risk factors of the values of 1 (better exposure) to 5 (worse exposure) corresponding to the exposure category. We entered the risk score into a logistic regression model and estimated the population attributable risk percent (PAR%) using the method of Bruzzi et al. RESULTS: After adjusting for age and family history of colorectal cancer and comparing the risk score for the combined six modifiable colon cancer risk factors at or above the approximate 20th, 10th, or 5th percentiles vs. below, the PAR% increased from 39% (95% confidence interval (CI) = 23-58%), to 48% (95% CI = 25-71%), to 55% (95% CI = 27-80%), respectively. Using a second method in which we used cut-points consistent with general-good health behaviors for each risk factor, comparing men with at least one risk factor to men without any risk factors (3.1% of the men), the PAR% was 71% (95% CI = 33-92%). CONCLUSION: The findings from this analysis suggest that, if all the members of this cohort of middle-aged US men had a modifiable exposure distribution comparable to the men with low risk scores, a large proportion of colon cancer risk might be avoidable. Additional study is required to determine whether making changes in these six risk factors now would reduce the risk of colorectal neoplasia, or whether the proportion of colon neoplasia that might be avoidable would be similar in populations with different characteristics.

Meta-analysis of dietary essential fatty acids and long-chain polyunsaturated fatty acids as they relate to visual resolution acuity in healthy preterm infants.

OBJECTIVE: To derive combined estimates of visual resolution acuity differences between healthy preterm infants consuming different compositions and ratios of essential fatty acids (EFAs) and docosahexaenoic acid (DHA), an omega-3 (n-3) long-chain polyunsaturated fatty acid (LCPUFA). DATA SOURCES: Electronic biomedical reference database (Medline and Health Star from 1965 to July 1999) searches with index terms omega-3, n-3, infant, vision, acuity, and human. Current review article, monograph, and book chapter bibliography/reference section hand searches. STUDY SELECTION: A total of 5 original articles and 4 review chapters were reviewed for details on study design, conduct, and outcome. Four prospective trials of EFA/LCPUFA supplementation were included in these analyses. For behaviorally based outcomes, there were 2 randomized comparisons each at

Dietary essential fatty acids, long-chain polyunsaturated fatty acids, and visual resolution acuity in healthy fullterm infants: a systematic review.

BACKGROUND: Biologically active neural tissue is rich in docosahexaenoic acid (DHA), an omega-3 long-chain polyunsaturated fatty acid (LCPUFA). We conducted a systematic review to examine the nature of discordant results from studies designed to test the hypothesis that dietary DHA leads to better performance on visually-based tasks in healthy, fullterm infants. We also conducted a meta-analysis to derive combined estimates of behavioral- and electrophysiologic-based visual resolution acuity differences and sample sizes that would be useful in planning future research. STUDY DESIGN AND METHODS: Twelve empirical studies on LCPUFA intake during infancy and visual resolution acuity were identified through bibliographic searches, examination of monograph and review article reference lists, and written requests to researchers in the field. Works were reviewed for quality and completeness of information. Study design and conduct information was extracted with a standardized protocol. Acuity differences between groups consuming a source of DHA and groups consuming DHA-free diets were calculated as a common outcome from individual studies; this difference score was evaluated against a null value of zero and then used, with the method of DerSimonian and Laird (Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-188), to derive combined estimates of visual resolution acuity differences within seven age categories. RESULTS OF RANDOMIZED COMPARISONS: The combined visual resolution acuity difference measured with behaviorally based methods between DHA-supplemented formula fed groups and DHA-free formula fed groups is 0.32+/-0.09 octaves (combined difference+/-S.E.M., P=0.0003) at 2 months of age. The direction of this value indicates higher acuity in DHA-fed groups. RESULTS OF NON-RANDOMIZED STUDY DESIGNS: The combined visual resolution acuity difference measured with behaviorally based methods between human milk fed groups and DHA-free formula fed groups is 0.49+/-0.09 octaves (P< or =0.000001) at 2 months of age and 0.18+/-0.08 octaves (P=0.04) at 4 months of age. Acuity differences for electrophysiologic-based measures are also greater than zero at 4 months (0.37+/-0.16 octaves, P=0.02). CONCLUSION: Some aspect of dietary n-3 intake is associated with performance on visual resolution acuity tasks at 2, and possibly, 4 months of age in healthy fullterm infants. Whether n-3 intake confers lasting advantage in the development of visually based processes is still in question.

A prospective study of vitamin supplement intake and cataract extraction among U.S. women.

We prospectively examined the association between vitamin supplement intake and the incidence of cataract extraction during 12 years of follow-up in a cohort of 47,152 female nurses. Women were 45 years or older and free of diagnosed cancer in 1980; others were added as they reached 45 years of age, for a total of 73,956 women. During 720,082 years of follow-up, 1,377 senile cataracts were diagnosed and extracted. Those who used multivitamins or separate supplements of vitamin C, E, or A did not have decreased risks of cataract as compared with nonusers even for use of 10 or more years. After adjusting for cataract risk factors, including cigarette smoking, body mass index, and diabetes mellitus, users of vitamin C supplements for 10 or more years had a relative risk (RR) of 0.95 [95% confidence interval (CI) = 0.76-1.20]. Associations were stronger among long-term vitamin C supplement users who were never-smokers (RR = 0.71; 95% CI = 0.47-1.08) and less than 60 years of age (RR = 0.72; 95% CI = 0.49-1.04). These findings suggest that there is little overall benefit of long-term use of vitamin supplements for risk of cataracts requiring extraction.

Prospective study of smoking, antioxidant intake, and lung cancer in middle-aged women (USA).

BACKGROUND: Although substantial evidence suggests that higher intake of fruits and vegetables can reduce the adverse impact of smoking on lung cancer risk, great uncertainty exists regarding the specific foods and their constituents that are protective. We therefore examine prospectively the relation between cigarette smoking and lung cancer incidence among women, and quantify the associations between dietary antioxidants, other nutrients, and lung cancer risk. METHODS: In a 16-year prospective cohort study (the Nurses' Health Study), 593 cases of lung cancer were confirmed during 1,793,327 person-years of follow-up. Dietary data, including vitamin supplement use and food intake, were collected in 1980 using a validated semiquantitative food frequency questionnaire. RESULTS: The risk of lung cancer increased with the number of cigarettes smoked and with early onset of cigarette smoking. The risk decreased rapidly with the discontinuation of smoking but took 15 years to fall to about the level of risk for women who had never smoked. Dietary intake of fat was not related to the risk of lung cancer. Although beta-carotene intake was not related to risk, intake of carrots showed a strong inverse relation: women who reported consuming five or more carrots per week had a relative risk of 0.4 (95% CI = 0.2-0.8) compared with the risk for women who never ate carrots. CONCLUSIONS: Smoking is the most important risk factor for lung cancer in women, as it is in men. Higher vegetable consumption, particularly of carrots, may significantly reduce the risk of lung cancer, but dietary modification cannot be considered a substitute for smoking prevention and cessation.

A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men.

CONTEXT: Coffee has several metabolic effects that could reduce the risk of gallstone formation. OBJECTIVE: To examine the association between coffee consumption and the risk of symptomatic gallstone disease in men. DESIGN AND SETTING: The Health Professionals Follow-up Study, a prospective cohort study, in which the consumption of coffee and other caffeinated drinks was assessed starting in 1986 as part of the 131-item food frequency questionnaire given to US male health professionals with follow-up through 1996. PARTICIPANTS: A total of 46008 men, aged 40 to 75 years in 1986, without history of gallstone disease. MAIN OUTCOME MEASURES: Newly symptomatic gallstone disease (diagnosed by ultrasonography or x-ray) or a cholecystectomy. RESULTS: During 404 166 person-years of follow-up, 1081 subjects reported symptomatic gallstone disease, of whom 885 required cholecystectomy. After adjusting for other known or suspected risk factors, compared with men who did not consume regular coffee in 1986 and 1990, the adjusted relative risk (RR) for those who consistently drank 2 to 3 cups of regular coffee per day was 0.60 (95% confidence interval [CI], 0.42-0.86) and for those who drank 4 or more cups per day the RR was 0.55 (95% CI, 0.33-0.92). All coffee brewing methods showed a decreased risk. The risk of symptomatic gallstone disease also declined with increasing caffeine intake (P for trend = .005). After controlling for known or suspected risk factors, the RR for men in the highest category of caffeine intake (>800 mg/d) compared with men in the lowest category (< or =25 mg/d) was 0.55 (95% CI, 0.35-0.87). In contrast, decaffeinated coffee was not associated with a decreased risk. CONCLUSIONS: In this cohort of US men, coffee consumption may have helped to prevent symptomatic gallstone disease.

A prospective study of folate intake and the risk of breast cancer.

CONTEXT: Folate is involved in DNA synthesis and methylation and may reduce breast cancer risk, particularly among women with greater alcohol consumption. OBJECTIVES: To assess the association between folate intake and risk of breast cancer and whether higher folate intake may reduce excess risk among women who consume alcohol. DESIGN: Prospective cohort study performed in 1980, with 16 years of follow-up. SETTING AND PARTICIPANTS: A total of 88818 women who completed the dietary questionnaire section of the Nurses' Health Study in 1980. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer by levels of folate and alcohol intake. RESULTS: A total of 3483 cases of breast cancer were documented. Total folate intake was not associated with overall risk of breast cancer. However, among women who consumed at least 15 g/d of alcohol, the risk of breast cancer was highest among those with low folate intake. For total folate intake of at least 600 microg/d compared with 150 to 299 microg/d, the multivariate relative risk (RR) was 0.55 (95% confidence interval [CI], 0.39-0.76; P for trend = .001). This association was only slightly attenuated after additional adjustment for intake of beta carotene, lutein/zeaxanthin, preformed vitamin A, and total vitamins C and E. The risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 microg/d (for alcohol intake > or =15 g/d vs <15 g/d, multivariate RR, 1.32; 95% CI, 1.15-1.50). For women who consumed at least 300 microg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol vs less than 15 g/d was 1.05 (95% CI, 0.92-1.20). Current use of multivitamin supplements, the major source of folate, was associated with lower breast cancer risk among women who consumed at least 15 g/d of alcohol (for current users of supplements vs never users, RR, 0.74; 95% CI, 0.59-0.93). CONCLUSIONS: Our findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.

Association of dietary intake of fat and fatty acids with risk of breast cancer.

CONTEXT: High intakes of fat and specific fatty acids, including total, animal, saturated, polyunsaturated, and trans-unsaturated fats, have been postulated to increase breast cancer risk. OBJECTIVE: To determine whether intakes of fat and fatty acids are associated with breast cancer. DESIGN AND SETTING: Cohort study (Nurses' Health Study) conducted in the United States beginning in 1976. PARTICIPANTS: A total of 88795 women free of cancer in 1980 and followed up for 14 years. MAIN OUTCOME MEASURE: Relative risk (RR) of invasive breast cancer for an incremental increase of fat intake, ascertained by food frequency questionnaire in 1980, 1984, 1986, and 1990. RESULTS: A total of 2956 women were diagnosed as having breast cancer. Compared with women obtaining 30.1% to 35% of energy from fat, women consuming 20% or less had a multivariate RR of breast cancer of 1.15 (95% confidence interval [CI], 0.73-1.80). In multivariate models, the RR (95% CI) for a 5%-of-energy increase was 0.97 (0.94-1.00) for total fat, 0.98 (0.96-1.01) for animal fat, 0.97 (0.93-1.02) for vegetable fat, 0.94 (0.88-1.01) for saturated fat, 0.91 (0.79-1.04) for polyunsaturated fat, and 0.94 (0.88-1.00) for monounsaturated fat. For a 1% increase in energy from trans-unsaturated fat, the values were 0.92 (0.86-0.98), and for a 0.1% increase in energy from omega-3 fat from fish, the values were 1.09 (1.03-1.16). In a model including fat, protein, and energy, the RR for a 5% increase in total fat, which can be interpreted as the risk of substituting this amount of fat for an equal amount of energy from carbohydrate, was 0.96 (95% CI, 0.93-0.99). In similar models, no significant association of risk was evident with any major types of fat. CONCLUSION: We found no evidence that lower intake of total fat or specific major types of fat was associated with a decreased risk of breast cancer.

Dietary carotenoids and vitamins A, C, and E and risk of breast cancer.

BACKGROUND: Data on intake of specific carotenoids and breast cancer risk are limited. Furthermore, studies of vitamins A, C, and E in relation to breast cancer risk are inconclusive. We have conducted a large, prospective study to evaluate long-term intakes of these nutrients and breast cancer risk. METHODS: We examined, by use of multivariate analysis, associations between intakes of specific carotenoids, vitamins A, C, and E , consumption of fruits and vegetables, and breast cancer risk in a cohort of 83234 women (aged 33-60 years in 1980) who were participating in the Nurses' Health Study. Through 1994, we identified 2697 incident cases of invasive breast cancer (784 premenopausal and 1913 postmenopausal). RESULTS: Intakes of beta-carotene from food and supplements, lutein/zeaxanthin, and vitamin A from foods were weakly inversely associated with breast cancer risk in premenopausal women. Strong inverse associations were found for increasing quintiles of alpha-carotene, beta-carotene, lutein/zeaxanthin, total vitamin C from foods, and total vitamin A among premenopausal women with a positive family history of breast cancer. An inverse association was also found for increasing quintiles of beta-carotene among premenopausal women who consumed 15 g or more of alcohol per day. Premenopausal women who consumed five or more servings per day of fruits and vegetables had modestly lower risk of breast cancer than those who had less than two servings per day (relative risk [RR] = 0.77; 95% confidence interval [CI] = 0.58-1.02); this association was stronger among premenopausal women who had a positive family history of breast cancer (RR = 0.29; 95% CI = 0.13-0.62) or those who consumed 15 g or more of alcohol per day (RR = 0.53; 95% CI = 0.27-1.04). CONCLUSIONS: Consumption of fruits and vegetables high in specific carotenoids and vitamins may reduce premenopausal breast cancer risk.