In many observational studies, a higher intake of individual antioxidants is inversely associated with lung cancer risk. Data from in vitro and animal experiments suggest that there are biochemical interactions among antioxidant nutrients; therefore, consideration of multiple antioxidants simultaneously may be important in terms of risk estimation. The authors constructed a dietary antioxidant index and evaluated its ability to predict lung cancer risk within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. At baseline (1985–1988), 27,111 Finnish male smokers aged 50–69 years completed a dietary questionnaire that assessed usual frequency of consumption and portion sizes for the previous 12 months. A total of 1,787 incident cases of lung cancer were identified during a follow-up period of up to 14.4 years (1985–1999). Principal components analyses were individually applied to the carotenoid, flavonoid, and vitamin E nutrient groups, and summation of retained principal component scores, plus selenium and vitamin C, yielded the composite antioxidant index. In multivariate proportional hazards models, the relative risks for lung cancer according to increasing quintiles of the antioxidant index were 1.00 (referent), 1.00 (95% confidence interval (CI): 0.87, 1.14), 0.91 (95% CI: 0.79, 1.05), 0.79 (95% CI: 0.68, 0.92), and 0.84 (95% CI: 0.72, 0.98) (p for trend = 0.002). These findings support the hypothesis that a combination of dietary antioxidants reduces lung cancer risk in male smokers.

BACKGROUND.: Adiposity has been linked inconsistently with prostate cancer, and few studies have evaluated whether such associations vary by disease aggressiveness.METHODS.: The authors prospectively examined body mass index (BMI) and adult weight change in relation to prostate cancer incidence and mortality in 287,760 men ages 50 years to 71 years at enrollment (1995–1996) in the National Institutes of Health‐AARP Diet and Health Study. At baseline, participants completed questionnaires regarding height, weight, and cancer screening practices, including digital rectal examinations and prostate‐specific antigen tests. Cox regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (95% CIs).RESULTS.: In total, 9986 incident prostate cancers were identified during 5 years of follow‐up, and 173 prostate cancer deaths were ascertained during 6 years of follow‐up. In multivariate models, higher baseline BMI was associated with significantly reduced total prostate cancer incidence, largely because of the relationship with localized tumors (for men in the highest BMI category [≥40 kg/m²] vs men in the lowest BMI category [<25 kg/m²]: RR, 0.67; 95% CI, 0.50–0.89; P = .0006). Conversely, a significant elevation in prostate cancer mortality was observed at higher BMI levels (BMI <25 kg/m²: RR, 1.0 [referent group]; BMI 25–29.9 kg/m²: RR, 1.25; 95% CI, 0.87–1.80; BMI 30–34.9 kg/m²: RR, 1.46; 95% CI, 0.92–2.33; and BMI ≥35 kg/m²: RR, 2.12; 95% CI, 1.08–4.15; P = .02). Adult weight gain from age 18 years to baseline also was associated positively with fatal prostate cancer (P = .009), but not with incident disease.CONCLUSIONS.: Although adiposity was not related positively to prostate cancer incidence, higher BMI and adult weight gain increased the risk of dying from prostate cancer. Cancer 2007. Published 2007 by the American Cancer Society.

Background Multivitamin supplements are used by millions of Americans because of their potential health benefits, but the relationship between multivitamin use and prostate cancer is unclear. Methods We prospectively investigated the association between multivitamin use and risk of prostate cancer (localized, advanced, and fatal) in 295344 men enrolled in the National Institutes of Health (NIH)–AARP Diet and Health Study who were cancer free at enrollment in 1995 and 1996. During 5 years of follow-up, 10241 participants were diagnosed with incident prostate cancer, including 8765 localized and 1476 advanced cancers. In a separate mortality analysis with 6 years of follow-up, 179 cases of fatal prostate cancer were ascertained. Multivitamin use was assessed at baseline as part of a self-administered, mailed food-frequency questionnaire. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by use of Cox proportional hazards regression, adjusted for established or suspected prostate cancer risk factors. Results No association was observed between multivitamin use and risk of localized prostate cancer. However, we found an increased risk of advanced and fatal prostate cancers (RR = 1.32, 95% CI = 1.04 to 1.67 and RR = 1.98, 95% CI = 1.07 to 3.66, respectively) among men reporting excessive use of multivitamins (more than seven times per week) when compared with never users. The incidence rates per 100000 person-years for advanced and fatal prostate cancers for those who took a multivitamin more than seven times per week were 143.8 and 18.9, respectively, compared with 113.4 and 11.4 in never users. The positive associations with excessive multivitamin use were strongest in men with a family history of prostate cancer or who took individual micronutrient supplements, including selenium, β-carotene, or zinc. Conclusion These results suggest that regular multivitamin use is not associated with the risk of early or localized prostate cancer. The possibility that men taking high levels of multivitamins along with other supplements have increased risk of advanced and fatal prostate cancers is of concern and merits further evaluation.

The mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear. We investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case–cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5–12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided. Insulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8% higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10% and 6% higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95% confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95% CI = 0.86 to 3.56; and OR = 2.55, 95% CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; P_trend = .02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; P_trend = .02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration ( P_trend = .38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100 000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100 000 person-years in the highest quartile. Elevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.

A meta-analysis of 19 trials suggested a small increase in the risk of all-cause mortality with high-dose vitamin E supplementation. Little is known, however, about the relation between mortality and circulating concentrations of vitamin E resulting from dietary intake, low-dose supplementation, or both. We examined whether baseline serum alpha-tocopherol concentrations are associated with total and cause-specific mortality. A prospective cohort study of 29 092 Finnish male smokers aged 50-69 y who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study was carried out. Fasting serum alpha-tocopherol was measured at baseline by using HPLC. Only 10% of participants reported vitamin E supplement use at baseline, and thus serum concentrations of vitamin E mainly reflected dietary intake and other host factors. Risks of total and cause-specific mortality were estimated by using proportional hazards models. During up to 19 y of follow-up, 13 380 deaths (including 4518 and 5776 due to cancer and cardiovascular disease, respectively) were identified. Men in the higher quintiles of serum alpha-tocopherol had significantly lower risks of total and cause-specific mortality than did those in the lowest quintile [relative risk (RR) = 0.82 (95% CI: 0.78, 0.86) for total mortality and 0.79 (0.72, 0.86), 0.81 (0.75, 0.88), and 0.70 (0.63, 0.79) for deaths due to cancer, cardiovascular disease, and other causes, respectively; P for trend for all < 0.0001]. Cubic regression spline analysis of continuous serum alpha-tocopherol values indicated greater risk reductions with increasing concentrations up to approximately 13-14 mg/L, after which no further benefit was noted. Higher circulating concentrations of alpha-tocopherol within the normal range are associated with significantly lower total and cause-specific mortality in older male smokers.

Education inequalities in cancer incidence have long been noted. It is not clear, however, whether such inequalities persist in the United States, especially for less common malignancies and after adjustment for individual risk factors. Within the NIH–AARP Diet and Health Study, we examined the association between education and the risk of developing cancers in a prospective cohort of 498 455 participants who were 50–71 year old and without cancer at enrollment in 1995/96. During a maximum 8.2 years of follow–up we identified 40 443 cancers in men and 18 367 in women. In age-adjusted models, the least educated men (<high school), compared to those with the most education (post–graduate), had increased risks of developing cancers of the esophagus (RR: 2.64, 95%CI:1.86–3.75), head and neck (1.98, 1.54–2.54), stomach (2.32, 1.68–3.18), colon (1.31, 1.12–1. 53), rectum (1.68, 1.32–2.13), liver (1.90, 1.22–2.95), lung (3.67, 3.25–4.15), pleura (4.01, 1.91–8.42), bladder (1.56,1.33–1.83) and combined smoking–related cancers (2.41, 2.22–2.62). In contrast, lower education level was associated with a decreased risk of melanoma of the skin (0.43, 0.35–0.54) and local prostate cancers (0.79, 0.74–0.85). Women with the least education had increased risks of colon (1.60, 1.24–2.05), lung (2.14, 1.79–2.56), kidney (1.68, 1.12–2.54) and combined smoking–related cancers (1.66, 1.43–1.92) but a lower risk of melanoma of the skin (0.33, 0.22–0.51), endometrial (0.67, 0.51–0.89) and invasive breast cancers (0.72, 0.61–0.84). Adjustment for smoking and other risk factors did not eliminate these associations, except those for cancers of the head and neck, colon, and liver in men and kidney in women. We found a higher risk of malignant disease, particularly smoking– related cancers, among those in the lowest educational attainment category. Only some of the educational gradient is attributable to smoking. The persistence of substantial education inequalities in cancer incidence poses a challenge for etiologic research and public health policy.