Vitamin C Intakes and Prostate Cancer Risk

Background: Vitamin E, β -carotene, and vitamin C are micronutrient antioxidants that protect cells from oxidative damage involved in prostate carcinogenesis. In separate trials, supplemental vitamin E was associated with a decreased risk of prostate cancer among smokers and supplemental β -carotene was associated with a decreased risk of prostate can cer among men with low baseline plasma β -carotene levels. Methods: We evaluated the association between intake of these micronutrient antioxidants from foods and supplements and the risk of prostate cancer among men in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. At baseline, trial participants completed a 137-item food frequency questionnaire that included detailed questions on 12 individual supplements. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confi dence intervals (CIs). All statistical tests were two-sided. Results: We identifi ed 1338 cases of prostate cancer among 29 361 men during up to 8 years of follow-up. Overall, there was no association between prostate cancer risk and dietary or supplemental intake of vitamin E, β carotene, or vitamin C. However, among current and recent (i.e., within the previous 10 years) smokers, decreasing risks of advanced prostate cancer (i.e., Gleason score ≥ 7 or stage III or IV) were associated with increasing dose (RR for >400 IU/day versus none = 0.29, 95% CI = 0.12 to 0.68; P trend = .01) and duration (RR for ≥ 10 years of use versus none = 0.30, 95% CI = 0.09 to 0.96; P trend = .01) of supplemental vitamin E use. Supplemental β -carotene intake at a dose level of at least 2000 μ g/day was associated with decreased prostate can cer risk in men with low (below the median of 4129 μ g/day) dietary β -carotene intake (RR = 0.52, 95% CI = 0.33 to 0.81). Among smokers, the ageadjusted rate of advanced prostate cancer was 492 per 100 000 person-years in those who did not take supplemental vitamin E, 153 per 100 000 person-years in those who took more than 400 IU/day of supplemental vitamin E, and 157 per 100 000 personyears in those who took supplemental vitamin E for 10 or more years. Among men with low dietary β-carotene intake, the ageadjusted rate of prostate cancer was 1122 per 100 000 personyears in those who did not take supplemental β-carotene, and 623 per 100 000 person-years in those who took at least 2000 μg/day of supplemental β-carotene. Conclusions: Our results do not provide strong support for population-wide implementation of high-dose antioxidant supplementation for the prevention of prostate cancer. However, vitamin E supplementation in male smokers and β carotene supplementation in men with low dietary β -carotene intakes were associated with reduced risk of this disease. [J Natl Cancer Inst 2006;98:245 – 54] Micronutrient antioxidants, including vitamin E, carotenoids, and vitamin C, neutralize free radicals ( 1 ) , which may play a role in prostate carcinogenesis by causing oxidative damage to DNA, lipid membranes, and proteins ( 2 ) . Vitamin E, which comprises a mixture of tocopherols, is a lipid-soluble antioxidant that is found in vegetable oils, nuts, whole grains, and other foods ( 3 ) . Carotenoids are found in a variety of orange or yellow fruits and vegetables as well as in some dark green leafy vegetables, including spinach and Brussels sprouts ( 4 ) . Vitamin C (ascorbic acid) is a water-soluble antioxidant found mainly in citrus fruits, strawberries, melons, tomatoes, broccoli, and peppers ( 5 ) . The most common carotenoids in the human diet include β -carotene, α -carotene, β -cryptoxanthin, lutein and zeaxanthin, and lycopene. Three large randomized trials have reported on the association between β -carotene supplementation and prostate cancer risk. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study found that male smokers who were randomly assigned to receive 20 mg of β -carotene daily experienced a nonsignifi cant increase in prostate cancer risk compared with those not receiving β -carotene ( 6 ) . The Physicians’ Health Study found that, overall, men who took 50 mg of β -carotene supplements on alternate days did not have a reduced risk of prostate cancer; however, among men with low plasma levels of β -carotene, those who took the supplements had a lower risk of prostate cancer than those who did not take supplements ( 7 ) . The β -Carotene and Retinol Effi cacy Trial (CARET) found no association between β -carotene supplementation and prostate cancer risk ( 8 ) . Vitamin E is the collective term for eight tocopherols and tocotrienols, with α , β , γ , and δ vitamers for each. Whereas γ tocopherol is the most prevalent form of vitamin E in the diet ( 9 ) , α -tocopherol (the form of vitamin E found in dietary supplements) is the most biologically available form because it is