Tomato products, lycopene, and prostate cancer: a review of the epidemiological literature.

In the past several years, 2 general lines of evidence have supported a role of lycopene in the prevention of certain malignancies, especially prostate cancer. First, important antioxidant properties of lycopene have been established (1). Given the relatively high concentrations of lycopene in the serum of many individuals and the potential role of oxidative stress in the formation or the progression of cancers, a potential anticancer influence of lycopene has been hypothesized. Second, a number of epidemiological studies have suggested that individuals with a relatively high intake of lycopene, particularly from tomato products, have a lower risk of prostate cancer (2). However, the association between tomato products or lycopene and lower prostate cancer risk, while suggestive, remains controversial, because not all the studies are supportive. The results from the epidemiological studies will be summarized here, and factors that may contribute to the apparent inconsistencies will be considered. There have been 2 basic study designs, those based on dietary intakes and those based on plasma or serum measures of lycopene. The dietary-based studies have been either retrospective (case control), in which prior recalled diet in men with prostate cancer is compared with that of a control or a comparison group free of prostate cancer, or prospective (cohort), in which diet is assessed in men initially free of cancer who are then followed for the occurrence of prostate cancer. The dietary studies have either been based on tomato or tomato-product intake or have estimated lycopene intake based on the intake of lycopene-containing foods. Results from a recent meta-analysis serve as a useful starting point in summarizing the results. This meta-analysis summarized results from studies published up to March 2003 (3). The authors identified 11 case-control studies and 10 cohort studies or nested case-control studies that presented data on the use of tomato, tomato products, or lycopene, and that met the inclusion criteria. The main findings were that, compared with nonfrequent users of tomato products (1st quartile of intake), the relative risk (RR) of prostate cancer among consumers of high amounts of raw tomato (5th quintile of intake) was 0.89 (95% CI 0.80–1.00). For a high intake of cooked tomato products, the corresponding RR was 0.81 (95% CI 0.71–0.92). The RR of prostate cancer related to an intake of 1 serving/d of raw tomato (200 g) was 0.97 (95% CI 0.85–1.10) for the case-control studies and 0.78 (95% CI 0.66–0.92) for cohort studies. For serumor plasma-based studies, the corresponding RRs were 0.74 (95% CI 0.59–0.92) for all studies, 0.55 (95% CI 0.32–0.94) for case-control studies, and 0.78 (95% CI 0.61–1.00) for cohort studies. The meta-analysis indicates that results from cohort studies and serumor plasma-based studies support about a 25–30% reduction in the risk of prostate cancer. The dietary-based case-control studies are generally not supportive, although 2 case-control studies that measured serum lycopene concentrations did find an inverse association with risk (3). Of 11 cohort studies of either diet or plasma, only 2 are nonsupportive. One of these studies, conducted in The Netherlands (4), found no appreciable association between tomato consumption and prostate-cancer risk. However, tomato consumption appeared to be low in this population. In the positive studies conducted in the United States, the average intake of lycopene may have exceed that in the Dutch study by about 10-fold. The other null cohort study was a study of prediagnostic serum carotenoids and prostate-cancer risk conducted between 1971 and 1993 in a Japanese-American population in Hawaii (5). In that study, a single assessment of serum lycopene was used to 1 Presented as part of the conference “Promises and Perils of Lycopene/ Tomato Supplementation and Cancer Prevention,” February 17–18, 2005, Bethesda, MD. This conference was sponsored by the Division of Cancer Prevention, Division of Cancer Epidemiology and Genetics, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services (DHHS); Office of Dietary Supplements (ODS), NIH, DHHS; and the Agricultural Research Services (ARS), USDA. Guest editors for the supplement publication were Cindy D. Davis, NCI, NIH; Johanna Dwyer, ODS, NIH; and Beverly A. Clevidence, ARS, USDA. 2 To whom correspondence should be addressed. E-mail: edward.giovannucci@channing.harvard. edu.