Karppi J, Kurl S, Nurmi T, Rissanen TH, Pukkala E, Nyyssönen K. Serum lycopene and the risk of cancer: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Ann Epidemiol. 2009 Jul;19(7): 512-518.

Cancer is a leading cause of death worldwide, second only to mortality associated with heart disease. It is thought that nutritional factors play an important role in the prevention of chronic diseases, such as cancer, and it has been estimated that nearly one-third of all cancer deaths in the United States could have been prevented through dietary modification. For example, diets rich in fruit and vegetables have been shown to be associated with a lower risk of many cancers. Among various phytochemicals the carotenoids in fruit and vegetables have shown "considerable promise" in preventing cancer because of their antioxidative ability to reduce oxidative stress—a risk factor for cancer. Of the many carotenoids, lycopene's ability to reduce the risk of prostate cancer has been studied the most. Dietary lycopene is derived primarily from tomatoes (Lycopersicon esculentum) and tomato products, but is also found in small amounts in pink grapefruit (Citrus x paradisi), watermelon (Citrullus lanatus), rose hip (Rosa spp.), apricot (Prunus armeniaca), guava (Psidium guajava), and papaya (Carica papaya). Lycopene is a potent antioxidant, and its anticancer activity has been shown both in vivo and in vitro. Its likely anticarcinogenic mechanisms of action include free radical scavenging, upregulation of detoxification systems, interruption of cell proliferation, and inhibition of cell cycle progression. The objective of the present study was to evaluate the association between serum lycopene concentrations and the risk of cancer in middle-aged eastern Finnish men in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) study.

The KIHD study is an ongoing, population-based, prospective study designed to investigate cardiovascular disease risk factors and related outcomes in middle-aged men from eastern Finland. Residents of Kuopio and the surrounding rural communities (n = 2682) aged 42, 48, 54, or 60 years were enrolled for the baseline examinations between March 1984 and December 1989. Reexaminations took place every 4 years thereafter. Nine hundred ninety-seven men from the Finnish cohort had serum lycopene data available from the reexaminations that took place between 1991 and 1993 and comprised the study population for the present study. During the examinations, blood samples were collected for the measurement of serum lycopene, retinol, a-tocopherol, a-carotene, b-carotene, and folate concentrations. Physical activity, smoking habits, alcohol consumption, education level, and family history of cancer were assessed. In addition, waist-to-hip ratio and body mass index were measured. All cancers diagnosed in Finland are recorded in the National Cancer Registry. The incidence and type of cancer that developed in the Finnish cohort were derived from this registry. All cancers diagnosed in the cohort between the time of study entry (March 1991 to December 1993) and 31 December 2006 were included in the analysis.

Over an average follow-up period of 12.6 years, 141 cancers were diagnosed: 55 prostate cancers, 17 lung cancers, 16 intestinal cancers, 10 urinary bladder cancers, and 43 cancers of other origin (e.g., stomach, lymphoma, skin, liver, kidney, and pancreas). The mean serum lycopene concentration was 0.12 mmol/L in the subjects who developed cancer and was 0.16 mmol/L in the subjects who did not develop cancer. Of the vitamins and carotenoids measured, serum lycopene was the only serum antioxidant that was significantly higher in men without cancer than in men with cancer and was the only carotenoid to have a negative correlation with cancer (r = -0.10, P = 0.003). More men with cancer than without cancer were smokers, and the duration of smoking was longer in the men with cancer than in those without cancer; smoking duration was inversely associated with serum lycopene concentration (r = -0.11; P < 0.0001). Men in the highest tertile of serum lycopene concentration had a 45% lower risk of overall cancer (risk ratio [RR] = 0.55; 95% confidence interval [CI] = 0.34–0.89; P = 0.015) and a 57% lower risk of other cancers (RR = 0.43; 95% CI = 0.23–0.79; P = 0.007) than did those in the lowest tertile of serum lycopene concentration after adjustment for the covariates age, examination years, family history of cancer, waist-to-hip ratio, duration of smoking, physical activity level, education level, alcohol consumption, and serum folate. No association between serum lycopene and prostate cancer was observed.

The results suggest that high serum lycopene concentrations may lower the risk of cancer, except for prostate cancer, in middle-aged men. However, the relatively small number of cancer cases in the cohort reduced the possibility of studying the risk of site-specific cancers. Also, the limitations to this study include obtaining only a single serum sample that simply demonstrates short-term dietary intake of lycopene due to its half-life of only a few days; multiple measurements would have been more precise.