Session 1: How Persuasive Is the Epidemiologic Evidence Suggesting a Role of Lycopene/Tomatoes in Cancer Prevention? Session Moderator: Christine Swanson, ODS, NIH What Do Epidemiologic Studies Suggest About Lycopene and/or Tomatoes as Modifiers of Prostate, Lung, or Colon Cancer Risk? Dr. Edward Giovannucci, Harvard University Dr. Giovannucci summarized the epidemiological literature on tomatoes, lycopene, and cancer. The epidemiologic evidence falls into four overlapping categories; retrospective case-control studies, prospective cohort studies, plasma-based studies, and questionnaire-based studies. Etminan, et al. (1) conducted a meta-analysis of 11 case-control and 10 cohort studies based on either plasma or dietary lycopene. They found: 1) a statistically significant inverse association between prostate cancer and serum lycopene (but not raw tomato intake, lycopene intake, or cooked tomato intake) in the case-control studies; and 2) a statistically significant inverse association between prostate cancer and raw tomato intake, lycopene intake, cooked tomato intake, and serum lycopene in the cohort studies and cohort/case-control studies combined, with a stronger inverse association in the cohort than combined group. Dr. Giovannucci concluded, from the work of Etminan, et al. (1) and others, that a moderate inverse association is observed between tomato products and prostate cancer in most prospective and plasma-based studies of lycopene. This association is unlikely to be caused solely by chance or bias and persists in most multivariate analyses, but residual confounders cannot be eliminated. Numerous case-control studies have reported inverse associations between tomato intake and risk of lung and gastric cancers, as well as several other cancers. Dr. Giovannucci stated that the studies of tomatoes, lycopene, and other cancers are suggestive, but not always consistent. In addition, few of the studies separated tomatoes from other fruits and vegetables, and almost no prospective or plasma-based studies have been conducted. Additional conclusions are that: 1) most dietary-based case-control studies (n = 7) do not support an association with lycopene; 2) most dietary-based cohort studies (n = 4), plasma-based cohort studies (n = 6), and plasma-based case-control studies (n = 2) support a 25 to 30 percent risk reduction; 3) this risk reduction is observed at lycopene intakes of approximately 10,000 mg/d or blood concentrations of approximately0.75 ìmol/L; 4) these associations are relatively modest, but if causal they are important because a single measure of diet and plasma would underestimate the true association; 5) the epidemiologic results apply only to tomato products (supplemental lycopene has not been studied); 6) although there is no obvious source of confounders, this cannot be excluded entirely; and 7) future research should include epidemiologic studies in diverse settings (e.g., non-United States), randomized intervention studies (prediagnostic and postdiagnostic), and studies to identify genetically susceptible groups. Discussion It was suggested that, because the association is strongest in the older group in which there is more obesity, the insulin-like growth factor-1 (IGF) might be involved. Dr. Giovannucci replied that, although the results are preliminary, he observed that IGF was associated with higher risk of prostate cancer in general, particularly for the more advanced cancers. When divided by grade, IGF was associated with better differentiated (lower grade and less advanced) cancers. He further speculated that cancers that are poorly differentiated, high grade and more advanced at diagnosis may be insensitive to endogenous or exogenous factors. In contrast, those that are better differentiated may be more susceptible to factors such as IGF. Lycopene and tomatoes also appear to be associated with better differentiated less advanced cancers. One participant asked if there is a potential interaction between lycopene and any other antioxidant that may contribute to the risk reduction profile. Dr. Giovannucci replied that, if lycopene acts as an antioxidant, interactions would be expected with selenium and vitamin E. When a high lycopene, high tocopherol, high selenium group of a population was compared to a group that was low in all of those factors, a highly significant, ten-fold difference in relative risk was observed in men with a specific variant of the manganese-dependent superoxide dismutase gene. This study should be replicated, but it suggests the presence of more susceptible groups. African-American men have a heightened risk of prostate cancer. One participant stated that the results of her case-control study showed that lycopene was inversely associated with risk in Caucasian and African-American men. It has been found that African-American men eat fewer tomatoes, and their lycopene levels are lower in blood. Dr. Giovannucci responded that only about 1 % of his study population was African American; however, even in such a small sample, he observed a statistically significant enhanced risk for prostate cancer among African-American men. He indicated that the African-American men in the study had a slightly lower intake of tomato products, but this study did not have the power to tease out the risk to this population. Another participant asked if there is any evidence that fat intake is a determinant of the response to lycopene or tomato products. Dr. Giovannucci replied that this issue has not yet been studied from an epidemiological perspective, but it could be in the future. 2/05 NIH Meeting February 2005 February 2005 February 2005 NIH Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. 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