The results of observational cohort studies that met the inclusion criteria are summarized in Appendix Table 1. Major features of each study are summarized below. Additional information about most studies is available in: Morris CD and Carson S. Vitamin supplementation to prevent cardiovascular disease, summary of the evidence for the U.S. Preventive Services Task Force available at www.ahrq.gov/clinic/uspstfix.htm.
1. The Netherlands Cohort Study.1,2 This study was designed to examine the association between intake of vitamins C and E, retinol, and beta-carotene and risk of breast cancer. Women from the general population aged 50-69 at baseline were eligible for enrollment. Of the 62,573 women enrolled, 96% continued for 3.3 years (median) of followup. The study found no relationship between the use of vitamin C supplements and breast cancer.
2. Nurses' Health Study I.3,4,5,6,7 This study was conducted in the United States and designed to determine whether vitamins A, C, E, folic acid, and multivitamin supplements are related to risk of colorectal adenomas. Female nurses aged 34-59 at baseline were eligible for enrollment. Of the 89,494 women enrolled, 96% continued for 8 years of followup participation.
3. Canadian National Breast Screening Study.8 This study was conducted in Canada and designed to examine the relationships of vitamins A, C, and E to risk of breast cancer. Women aged 40-59 at baseline who were involved in an ongoing breast cancer screening study were eligible for enrollment. Of the 56,837 qualified study subjects, 96% continued for 5 years of followup participation.
4. Leisure World Study.9,10 This US study was designed to examine the relationships of vitamins A, C, and E to risk of lung, colon, bladder, prostate, and breast cancers. Males and females living in the Leisure World retirement community were eligible for enrollment. The average age of the 70,159 qualified study subjects (24,218 men and 45,941 women) was mid-70's. Four- to 8-year followup rates were 99% for vital status and 85% for incident cancers. Statistical adjustment was made for age and smoking but not for other confounders.
5. Health Professionals' Follow-up Study.11,12 This study was conducted in the United States and designed to examine the relationships of folic acid, beta carotene and vitamins C and E to risk of colon cancer. Male dentists, osteopaths, optometrists, podiatrists, pharmacists, and veterinarians aged 40-75 were eligible for participation. Of the 43,738 qualified study subjects, 96% continued for 4 years of followup participation.
6. Iowa Women's Health Study.13,14,15 This study, conducted in the United States, was designed to investigate whether high intakes of antioxidant micronutrients (vitamins A, C, and E and beta-carotene) protect against colon and breast cancers. Women living in Iowa in 1986 who were aged 55-69 years at baseline and did not have a history of cancer were eligible for participation following completion of a dietary questionnaire. Of the 34,486 qualified study subjects, 84% continued for 5 years of followup participation.
7. National Health and Nutritional Examination Survey I.16 This US study was designed to examine the relation between vitamin C intake and cancer and all-cause mortality. Noninstitutionalized US adults aged 25-74 years at baseline who were nutritionally examined during 1971-1974 as part of an epidemiological followup study (NHANES I) were eligible for participation. Of the 14,407 qualified study subjects, 93% continued for 10 years (median) of followup participation.
8. Established Populations for Epidemiologic Studies of the Elderly.17 This study was conducted in the United States and designed to examine vitamin E and vitamin C supplement use in relation to mortality risk and whether vitamin C enhanced the effects of vitamin E. Residents of 4 east coast communities who were older than 65 at baseline (range 67-105) and who were involved in the Established Populations for Epidemiologic Studies of the Elderly in 1984-1993 were eligible for enrollment. Of the 11,178 qualified study subjects, 100% continued for 6 years of active participation and an additional 2-3 years for mortality followup. Adjustment was made for alcohol use, smoking history, aspirin use, and medical conditions.
9. Cancer Prevention Study II.18 This study was conducted in the United States and designed to determine the relation between multivitamin use and cancer and all-cause mortality. American Cancer Society volunteers recruited men and women aged 30 years and older for participation. The percentage of the 1,063,023 (453,962 men and 609,061 women) eligible study subjects who continued for the 7-year followup participation period is unclear.
10. Substudy of Polyp Prevention Study.19 Conducted in the United States, this study was designed to determine the relation between folate and multivitamin use and adenomatous polyp recurrence. Adults who were involved in the Polyp Prevention Study were eligible for enrollment. Eligible study subjects were 79% male and an average age of 60 years. The percentage of the 709 participants that completed the 4-year followup colonoscopy is unclear.
11. Nurses' Health Study and Health Professionals' Followup Study.4 This analysis was designed to measure the association of folate and methionine to risk for colorectal adenoma. Female nurses aged 34-59 from the Nurses' Health Study started in 1976. Male dentists, osteopaths, optometrists, podiatrists, pharmacists, and veterinarians aged 40-75 from the Health Professionals Followup Study, all of whom had undergone an endoscopy, were eligible for participation, started in 1986. Combined 4-year followup rates for the 9490 male subjects and 10-year followup rates for the 15,984 females subjects were 96% for standardized questionnaire completion and 91% for response to letter following adenomatous polyp recurrence.
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