Elizabeth C. Miller

Tomatoes, Lycopene, and Prostate Cancer: Progress and Promise

Prostate cancer has emerged as a major public health problem in nations that have an affluent culture with an aging population. The search for etiologic risk factors and an emphasis on the development of chemopreventive agents has gained momentum over the last decade. Among the landmark epidemiologic findings during this period has been the association between the consumption of tomato products and a lower risk of Prostate cancer. The traditional reductionist scientific approach has led many investigators to propose that lycopene, a carotenoid consumed largely from tomato products, may be the component responsible for lowering the risk of prostate cancer. Thus, many laboratory and clinical studies are now underway with the goal of assessing the ability of pure lycopene to serve as a chemopreventive agent for prostate and other malignancies. The focus on lycopene should continue, and an improved understanding of lycopene absorption, distribution, role in antioxidant reactions, and metabolism is critical in the quest to elucidate mechanisms whereby this compound could possibly reduce prostate cancer risk. In contrast to the pharmacologic approach with pure lycopene, many nutritional scientists direct their attention upon the diverse array of tomato products as a complex mixture of biologically active phytochemicals that together may have anti–prostate cancer benefits beyond those of any single constituent. These contrasting approaches will continue to be explored In clinical, laboratory and epidemiologic studies in the near future, providing hope that the next generation will benefit from this knowledge and experience a lower risk of prostate cancer.

Tomato products, lycopene, and prostate cancer risk

Several case-control and large prospective studies focusing on dietary assessment suggest that the intake of tomatoes and tomato products may be associated with a lower risk of prostate cancer [18]. Although less certain at present, the accumulated data suggest that the benefit may be most pronounced in the protection against more advanced or aggressive prostate cancer. It is possible that lycopene is one of the compounds in raw and processed tomato products that may contribute to a lower risk of prostate cancer; however, this hypothesis remains to be further investigated. Other carotenoids and phytochemicals in tomato products may also contribute to the proposed health benefits. Food processing does not seem to reduce the benefits but may, in fact, enhance the bioavailability of beneficial components. The reported correlations or associations between the consumption of tomato products and prostate cancer risk should not be interpreted as causal until additional data are available from a variety of studies in different populations. Ideally, randomized controlled intervention studies would provide an ultimate test of the tomato/lycopene hypothesis; however, the expense, long duration of exposure, and the near universal consumption of tomato products among Americans make a dietary intervention study difficult to undertake. It is reasonable to recommend to the general population the consumption of tomato products at approximately one serving per day or five servings per week as part of an overall healthy dietary pattern that may reduce the risks of prostate cancer, other malignancies, or other chronic diseases. This recommendation is consistent with current dietary guidelines to increase fruit and vegetable consumption to lower the risk of heart disease and many types of cancer [38]. Nutritional prevention of prostate cancer is very different from the use of dietary or nutritional treatments for established prostate cancer. The use of lycopene and other extracts for the treatment of prostate cancer is a separate issue that warrants individual attention and investigation.

Lycopene, tomato products, and prostate cancer prevention. Have we established causality?

The relationship between tomato products and prostate cancer prevention has been the subject of increasingly intense research activity over the past decade. The hypothesis that tomato products contain phytochemicals, perhaps lycopene and others, that modify prostate carcinogenesis warrants investigation. However, scientists, regulatory agencies, marketers of products, and those defining public health policy have differing opinions regarding the strength of the data when applied to criteria for inference and causality. It is useful to briefly review these criteria and discuss the relative strengths and weaknesses of the published data in order to better define future directions for research. Accepted categories of criteria include: consistency, strength of association, biological gradient, temporality, specificity, biological mechanisms and coherence, and experimental evidence. We believe that continued support for research regarding tomato products, lycopene and other phytochemicals, and prostate cancer risk is warranted and may ultimately serve as the basis for more consistent public health recommendations for the consumer. But, what do we say to the public when the data is still inconclusive? The authors support the recommendation that a minimum of five servings of fruit and vegetables should be consumed daily from a variety of sources. We believe that the hypothesized benefits of tomato products for prostate cancer prevention may be achieved with approximately five servings of tomato products per week. The consumption of lycopene supplements is not currently recommended for prostate cancer prevention or therapy. Future research will allow us to provide more definitive guidelines.

Tomatoes, lycopene and prostate cancer: a clinician's guide for counseling those at risk for prostate cancer.

Prostate cancer has become a major public health issue and the search for etiologic risk factors and the development of chemopreventive agents has gained momentum over the last decade. An important epidemiologic finding has been the association between the consumption of tomato products and a lower risk of prostate cancer. Several investigators have proposed that lycopene, a carotenoid consumed largely from tomato products, may be the component responsible for lowering the risk of prostate cancer. Laboratory and clinical studies have been initiated with the goal of assessing the ability of pure lycopene to serve as a chemopreventive agent for prostate cancer. The focus on lycopene should continue, and an improved understanding of lycopene absorption, distribution, role in antioxidant reactions, and metabolism is critical in the quest to elucidate mechanisms whereby this compound may possibly reduce prostate cancer risk.

CHEMOPREVENTION: PROGRESS AND OPPORTUNITY

A generally accepted definition of chemoprevention is the administration of purified chemical agents for the prevention of clinical cancer. This concept is commonly thought to have emerged a little over two decades ago and is attributed to cancer biologists who were elucidating the role of various natural substances and pharmacologic agents on the stepwise progression of cancer.26 However, a brief review of public health and medical advances over the twentieth century will reveal that the concept and application of chemoprevention for various disease processes evolved directly from the great successes of nutritional scientists in the early decades of this century. Regardless of the conceptual origins of cancer chemoprevention, the progress in identifying agents, testing them in preclinical models, followed by human intervention studies, has rapidly accelerated in recent years. The century ends with the success of the Breast Cancer Prevention Trial (BCPT) illustrating the ability of the anti-estrogen Tamoxifen to prevent breast cancer in a cohort of women at high-risk.10 Indeed, it is our opinion that chemoprevention, tobacco control, and the application of early detection strategies provide the opportunity to reduce cancer mortality by at least 50% within a generation.11 The objective of this review is to provide the broad audience of cancer prevention investigators with a brief overview of the progress and future promise of cancer chemoprevention.