Prostate news article, December 2009

CAN LIFESTYLE LOWER THE RISK OF PROSTATE CANCER?   Article by:   Professor Roger Kirby, Chairman, Prostate UK, Professor Michael Kirby, University of Hertfordshire and Professor John Fitzpatrick, Mater Hospital, Dublin

It is now accepted that lifestyle modification can significantly reduce the risk of both cardiovascular disease and diabetes. Accordingly, patients considered at risk are often exhorted to increase their exercise levels and eat more healthily. But what is the evidence that such lifestyle changes may also be valuable in reducing the risk of prostate cancer?

With respect to diet, it is known that the incidence of prostate cancer in Asia is increasing in parallel with the rising consumption of a Western-style diet. In a recent study the incidence of prostate cancer in Singapore rose by 5.6% per annum between 1968 and 2002. During the same period the mortality from the disease increased 5.8 fold¹. In a study from the 1980’s prostate cancer mortality correlated strongly with the intake of dietary fat². However, subsequent studies have provided less certitude³, in a meta-analysis of case control and prospective studies a higher intake of total fat was associated with only a slightly higher overall risk of prostate cancer. Saturated fat intake was more strongly associated with advanced prostate cancer⁴. In a recent prospective study of 142,520 European men there was no clear association between dietary fat and prostate cancer⁵. Similar uncertainties exist about a positive association between obesity and prostate cancer⁶.

Evidence on meat consumption and the risk of prostate cancer is somewhat stronger, but still far from conclusive. In a review of 22 studies on dietary meat 16 showed a positive correlation and the association was strongest for processed meats and those grilled with charcoal⁷. Diary products and calcium intake have also been linked to an increase prostate cancer risk. In a meta-analysis of 16 trials dairy products were found to increase risk only slightly but a high calcium intake (possibly as a result of a high consumption of milk and other diary products) had a strong positive correlation⁸.

Several studies have reported a negative correlation between moderate intensity exercise and prostate cancer risk^9-10. Although the mechanism remains uncertain, exercise has been shown to decrease serum levels of metabolic and steroid sex hormones hypothesized to stimulate prostate cancer, including insulin-like growth factor-1 (ILGF-1), insulin, leptin and testosterone. Exercise is also a potent stimulator of endogenous antioxidant protection pathways, thereby decreasing lipid peroxidation and reducing reactive oxygen species. Furthermore, exercise may improve innate immune function and surveillance, thereby protecting the individual against this disease and other cancers.

In a very recent report by Antonelli et al¹¹, 190 men who underwent prostate biopsy were assessed for their exercise level using the Godwin Leisure Time Exercise Questionnaire. Men who reported 9 or more metabolic equivalent task hours per week of exercise were significantly less likely to have cancer on biopsy. Furthermore, among men with malignant biopsy results, reporting moderate exercise (3 – 8.9 metabolic equivalent task hours weekly) was associated with a lower risk of high grade (ie Gleason 7 or greater) disease (p = 0.04).

If lifestyle modification were to become a regular component of the advice urologists deliver, then it would be most convenient if there were a way of identifying those men who are especially likely to develop the disease, because they would be the group who might be anticipated to benefit the most. Fortunately a framework for the identification of men at increased risk for prostate cancer has recently been published¹². Prostate specific antigen (PSA) turns out to be the most significant predictive factor. In the Baltimore Longitudinal Study of Aging for example, a longitudinal study in which men with a PSA greater than 4 ng/ml and/or suspicious DRE underwent prostate biopsy, a PSA greater than the age adjusted median was associated with a relative risk of 3.6 of being diagnosed with prostate cancer with a median follow up of 13 years¹³. A suspicious DRE, a family history of prostate cancer, the presence of high grade intra-epithelial neoplasia or atypical small acinar proliferation and black ethnicity are all important predictive factors, while a larger prostate volume and previous negative prostate biopsies are negative predictors. For men between 50 and 70 a PSA of more than 1.5 ng/ml is a marker for greater than average risk up to 8 years. Moreover 29 specific genetic mutations have now been associated with increased prostate cancer risk¹⁴ and in the future genetic profiling may identify a sub-group for whom enhanced surveillance and active risk reduction strategies, including lifestyle modification, might be appropriate.

In conclusion, although there is some circumstantial evidence in support of the proposal, it is still unclear whether lifestyle modification is capable of significantly reducing the risk of prostate cancer. The results of recent large-scale studies have provided conflicting evidence for dietary agents that were previously thought to have a positive association. However, advice designed to reduce the intake of saturated fats and red (especially barbequed) meats and to increase the amount of regular, reasonably strenuous exercise certainly will do no harm, and should afford protection against the development of cardiovascular disease and diabetes. As the urologist increasingly takes on the mantle of the specialist in Men’s Health¹⁵, it seems logical that he or she addresses the important issue of lifestyle with patients, especially those who are overweight and underactive.

References:
1. Chia SE, Tan CS Lim GH et al. Incidence, mortality and survival patterns of prostate cancer among residents in Singapore from 1968 to 2002. BMC Cancer 2008 8:368
2. Rose DP, Boyar AP, and Wynder EL. International comparisons of mortality rates for cancer of the breast, ovary, prostate and colon per capita food consumption. Cancer 1986 58:2363.
3. Colli JL, and Colli A. Comparisons of prostate cancer mortality rates with dietary practices in the United States. Urol Oncol 2005 23:390.
4. Dennis L, Snetsellaar LG, Smith BJ, et al. Problems with the assessment of dietary fat in prostate cancer studies Am J Epidemiol 2004; 160:436.
5. Crowe FL, Key TJ, Appleby PN. Dietary fat intake and the risk of prostate cancer in the European Prospective Investigation into Cancer Nutrition. Am J Clin Nutr 2008;87:1405.
6. Goldstraw MA, Besrani D, Amoroso P, Kirby RS. Is obesity a risk factor for prostate cancer? BJU Int. 2007;100:726-8 7. Kolonel LN, Fat meat and prostate cancer, Epidemiol Rev 2001;23:72
8. Gao X, LaValley MP and Tucker KL, Prospective studies of diary product and calcium intakes and prostate cancer risk: a meta-analysis. J Natl Cancer Inst 2005 97: 1798.
9. Giovannucci EL, Liu Y, Leitzmann MF et al. A prospective study of physical activity and incident and fatal prostate cancer. Arch Intern Med 2005;165:1005.
10. Antonelli J, Freeland SJ, Jones LW, Exercise therapy across the prostate cancer continuum Prostate Cancer Prostatic Dis 2009 12:110.
11. Antonelli J, Jones LW, Banez LL, et al Exercise and prostate cancer risk in a cohort of veterans undergoing prostate needle biopsy. J Urol 2009: 182:2226-31.
12. Roobol MJ, Schroder FH, Crawford ED et al. A framework for the identification of men at increased risk for prostate cancer. J Urol 2009; 182:2112-22.
13. Fang J, Metter EJ, Landis P et al. Low levels of prostate-specific antigen predict long-term risk of prostate cancer: results from the Baltimore Longitudinal Study of Aging Urology 2001; 58:411.
14. Kirby RS, Eeles R et al Screening for prostate cancer: the way ahead. BJUI 2010 in press.
15. Kirby RS The urologist as the advocate of men's health. BJU Int. 2005; 95:929.