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reference
To K, Mucci L, Rosner BA, et al. Dietary lycopene, angiogenesis and prostate cancer: a prospective study in the prostate-specific antigen era.J Natl Cancer Inst. 2014;106(2):djt430.
design
Ongoing prospective cohort study
Study participants
In 1986, 51,529 male U.S. health professionals (dentists, optometrists, osteopaths, podiatrists, pharmacists, and veterinarians) between the ages of 40 and 75 years participated in this study.
Evaluated study parameters
Dietary intake was assessed every four years from 1986 to 2006 using a self-administered semiquantitative food frequency questionnaire. Dietary lycopene content was calculated based on data from the US Department of Agriculture. Plasma lycopene values were also available for some of the men in the study (n=1,200), for whom quintiles with the highest to lowest lycopene values were identified. Prostate cancer diagnoses were self-reported in a biennial questionnaire. Medical records were reviewed for data on tumor stage, prostate-specific antigen (PSA) at diagnosis, Gleason score, angiogenic biomarkers, apoptosis, and proliferation. Deaths due to prostate cancer were confirmed through review of medical records, death certificates, and National Death Index searches. To assess whether PSA screening influences the association between lycopene intake and prostate cancer incidence, stratified survival analyzes were performed before and after the introduction of PSA testing in 1994.
Primary outcome measures
Overall incidence of prostate cancer in relation to dietary lycopene intake; Incidence of fatal or metastatic prostate cancer associated with dietary intake; and markers of tumor angiogenesis, apoptosis and proliferation associated with dietary lycopene intake.
Key findings
Compared to the lowest quintile of dietary lycopene consumption, the top quintile showed an inverse association between overall prostate cancer incidence and early lycopene intake (hazard ratio). [HR]: 0.91; 95% confidence interval [CI]: 0.84–1.00). A stronger inverse association was found between fatal prostate cancer and lycopene intake (HR: 0.72; 95% CI: 0.56-0.94). The strongest inverse association was found in men who had the highest intake at baseline and maintained that intake (HR: 0.48; 95% CI: 0.30-0.78), as opposed to those who increased their intake over time. Before the introduction of PSA testing into clinical practice, high lycopene intake was found to have a stronger inverse association with the total number of prostate cancers diagnosed. However, only a small reduction in overall prostate cancer diagnoses was noted in the PSA era. However, the lower risk of fatal prostate cancer remained unchanged. There was a strong association between higher lycopene intake and markers of angiogenesis in the subjects with prostate cancer. These men had tumors with much lower angiogenic potential. Markers of tumor apoptosis and proliferation showed no association with lycopene intake.
Effects on practice
This study is the latest of many attempting to elucidate the connection between lycopene and its possible role in preventing or treating prostate cancer. The large size (N=51,529) and long duration of the study give us a more comprehensive insight into how lifelong habits can influence prostate cancer. The study also gives us an important perspective on how a food ingredient, rather than an isolated compound, can alter the course of a disease over time. The data from this study can be used as a tool to help physicians educate their patients about habits that promote wellness throughout their lives. Theoretically, lycopene appears to be an ideal cancer prevention agent. It is the most powerful antioxidant of all carotenoids and activates antioxidant enzymes such as glutathione S-transferase and superoxide dismutase.1This means it can prevent cell and DNA damage. There are also many studies that have shown lycopene's ability to interfere with the growth of prostate cancer cells in culture.1-3However, there are mixed data about how lycopene affects prostate cancer in people.
Men with the highest dietary lycopene intake also generally consumed more fruits, vegetables and fiber, which has been shown to reduce the risk of prostate cancer.
While previous studies showed a more consistent association between an overall diagnosis of prostate cancer and high lycopene intake, studies over the past 10 years have found mixed results.4-9According to the present study, since the introduction of PSA testing, there has been a smaller difference in the number of prostate cancers diagnosed relative to lycopene intake. However, the research team found a significant difference in the incidence of fatal or metastatic prostate cancer in men with the highest and lowest levels of dietary lycopene. It may be that prostate cancer is being diagnosed much earlier since the introduction of PSA testing. This also implies that lycopene influences the growth of prostate cancer instead of preventing the tumors from forming. Supporting this notion, men with higher lycopene intake and prostate cancer had significantly different markers of angiogenic potential, meaning their tumors were less aggressive.
While there is controversy over the practical value of universal PSA screening due to the overdiagnosis and treatment of indolent cancers,10,11In this particular study, PSA was a useful surrogate for later biopsy-proven cancers and their association with lycopene intake. The group members who showed the greatest benefit initially consumed the highest amount of lycopene and continued to do so throughout the years of the study, in contrast to the men who began consuming higher dietary lycopene intakes later. Ideally, incorporating foods high in lycopene early into the diet will have the most profound impact on the men who go on to develop prostate cancer.
As with all whole food studies, other factors may also play a role. For example, foods high in lycopene may contain other chemicals that could be responsible for the results or have a synergistic effect with lycopene in the body. This study used data calculated from reported intake of lycopene-containing foods rather than supplemented lycopene. Other studies using whole tomato products have also shown positive results.12,13while studies with supplemented lycopene have shown less benefit.11,14,15Additionally, other phytochemicals such as alpha-tomatine, a saponin found in tomatoes, have been found to inhibit the growth of prostate cancer cells in cell cultures and in mice.16,17It is also important to consider whether other factors besides the consumption of foods high in lycopene played a role in these results. For example, in this study, the men with the highest dietary intake of lycopene also generally consumed more fruits, vegetables, and fiber, which have been shown to reduce the risk of prostate cancer.18.19
This study is a good long-term look at how consumption of a particular class of food can help alter the course of a disease process over time. In the short term, it is less clinically relevant for patients with prostate cancer because the effects of lycopene-rich foods on prostate cancer are more pronounced when long-term consumption is initiated before the diagnosis of prostate disease. However, the results of the study can help doctors advise their patients about their eating habits. It highlights the need for quality nutritional advice as a crucial part of the prevention aspect of a routine check-up. This gives primary care physicians another tool to improve the long-term health of their patients.