Lower prostate cancer risk in men with elevated plasma lycopene levels: Results of a prospective analysis

Dietary consumption of the carotenoid lycopene (mostly from tomato products ) has been associated with a lower risk of prostate cancer. Evidence relati ng other carotenoids, tocopherols, and retinol to prostate cancer risk has been equivocal. This prospective study was designed to examine the relation ship between plasma concentrations of several major antioxidants and risk o f prostate cancer. We conducted a nested case-control study using plasma samples obtained in 1 982 from healthy men enrolled in the Physicians' Health Study, a randomized , placebo-controlled trial of aspirin and beta-carotene, subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1294 age- and smoking status-matched controls. We quantified the five major pla sma carotenoid peaks (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and Lycopene) plus alpha- and gamma-tocopherol and retinol using high-perf ormance liquid chromatography. Results for plasma beta-carotene are reporte d separately. Odds ratios (ORs), 95% confidence intervals (CIs), and Ps for trend were calculated for each quintile of plasma antioxidant using logist ic regression models that allowed for adjustment of potential confounders a nd estimation of effect modification by assignment to either active beta-ca rotene or placebo in the trial. Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls (P = 0.04 for all cases). The ORs for all prostate cancers declined slightly with increasing quintile of plasma lyco pene (5th quintile OR = 0.75, 95% CI = 0.54-1.06; P, trend = 0.12); there w as a stronger inverse association for aggressive prostate cancers (5th quin tile OR = 0.56, 95% CI = 0.34-0.91; P, trend = 0.05). In the placebo group, plasma Lycopene was very strongly related to lower prostate cancer risk (5 th quintile OR = 0.40; P, trend = 0.006 for aggressive cancer), whereas the re was no evidence for a trend among those assigned to beta-carotene supple ments. However, in the beta-carotene group, prostate cancer risk was reduce d in each Lycopene quintile relative to men with low lycopene and placebo. The only other notable association was a reduced risk of aggressive cancer with higher alpha-tocopherol levels that was not statistically significant. None of the associations for lycopene were confounded by age, smoking, bod y mass index, exercise, alcohol, multivitamin use, or plasma total choleste rol level. These results concur with a recent prospective dietary analysis, which iden tified Lycopene as the carotenoid with the dearest inverse relation to the development of prostate cancer. The inverse association was particularly ap parent for aggressive cancer and for men not consuming beta-carotene supple ments. For men with low lycopene, beta-carotene supplements were associated with risk reductions comparable to those observed with high lycopene. Thes e data provide further evidence that increased consumption of tomato produc ts and other lycopene-containing foods might reduce the occurrence or progr ession of prostate cancer.