Fall 2011 - Institute of Medical Science - University of Toronto

More documents

Recommendations

Info

FEATURE The Role of Diet and Exercise in Prostate Cancer Dr. Vasundara Venkateswaran PhD Associate Professor of Surgery, University of Toronto The fact that prostate cancer is one of the most prevalent cancers has enormous public health significance. With nearly 25,000 new cases each year, prostate cancer is a growing problem. Hence, strategies for prevention of this disease would attenuate its economic, emotional, physical and social impact. Both the substantial variation in the incidence of prostate cancer worldwide and the increased risk in the migrant population (moving from lowrisk to high-risk countries) provide strong support for modifiable environmental factors – particularly diet – in prostate cancer etiology. Over the years, dietary agents have gained considerable attention as chemopreventive agents against prostate cancer. Studies suggest that men can reduce their risk of prostate cancer by making sure they maintain a healthy diet. Dietary factors are one of the major elements accounting for the international and inter-ethnic differences in the rate of prostate cancer 1 . Many agents have been evaluated for their primary and secondary chemopreventive capacities, including soy proteins, tomatoes and lycopene, vitamin E, selenium, fish and marine fats, ω-3 fatty acids, cholesterol, polyphenols, isoflavones, red meat, pomegranate, cruciforms and green tea 2-7 . There are numerous review articles that discuss mechanisms of action and implications of dietary agents for chemoprevention of prostate cancer 8 . These compounds potentially interact with a range of carcinogenic pathways, including androgen metabolism, cell cycle processes and apoptosis, maintenance of mitochondrial membrane potentials, insulin-like growth factor (IGF)-Akt signaling and response to oxidative stress. It is interesting to note that nutrient intake can modify genetic susceptibility to diseases such as cancer 9 . This information is helpful in providing a scientific basis for cancer prevention via dietary modification. It is essential to appreciate that diet provides multiple micronutrients and macronutrients packaged in their most effective form, since diet is an important aspect of health that an individual can control. Currently, the strongest association between diet and prostate cancer appears to be obesity. Prior research conducted in our laboratory has suggested that energy balance and fat intake influence prostate cancer progression. However, the influence of dietary carbohydrates on prostate cancer progression has not been well characterized. Hence, we tested if hyperinsulinemia resulting from high intake of refined carbohydrates would lead to more rapid growth of tumors in the xenograft mouse model of prostate cancer. Interestingly, this diet was associated with increased tumor growth, with activation of signaling pathways distal to the insulin receptor 10 . Our research lends support to the concept that diets associated with a reduction in insulin levels may have benefits for prostate cancer patients, particularly for a hyperinsulinemic subset of the population. Furthermore, it also provides the rationale for clinical research attempting to determine if lower prostate cancer risk and/ or improved prostate cancer prognosis can be obtained through minimization of insulin levels and optimization of macronutrient intake to meet, but not exceed, nutritional requirements. Ongoing investigations of pharmacologic agents such as metformin (a compound that reduces hyperinsulinemia and associated metabolic abnormalities) examine if such compounds may also have a role to play in the treatment of metabolicallydefined subsets of prostate cancer patients. Besides identification of molecular targets, other methods of prevention would have to be incorporated into a prostate cancer prevention strategy. These include personalized risk assessment and discovery of biomarkers, Photo by Connie Sun 17 | IMS MAGAZINE FALL 2011 PROSTATE CANCER
FEATURE Photo courtesy of http://www.sxc.hu/photo/816375 sensitivity to preventive agents, and surrogate molecular markers serving as intermediate end points. Despite all this, one has to recognize that the intrinsic heterogeneity of any given study population makes nutritional studies difficult to perform. This is due to several factors including variations in individual lifestyles, complexity in food and food products, as well as the levels of consumption of such foods. Laboratory studies in preclinical animal models provide important guidelines in designing, conducting, and interpreting large studies in humans; however, complications and errors arise while translating data from animal studies to the clinical setting. This demonstrates the complexity in interpreting many of the contradictory reports that can confuse researchers, physicians and the public alike. Recent evidence highlights not only the role of dietary factors but also the inclusion of physical activity as a key component in the development and progression of prostate cancer. Epidemiological and laboratory investigations indicate a negative relationship between regular exercise and the risk of certain malignancies, including prostate cancer. A recent review 11 has discussed the influence of physical activity on the carcinogenic process, where physical activity is dependent on energy contribution and the duration of exercise. There are several probable biological mechanisms projected to explain the cancer-preventive effects of exercise, including changes in endogenous metabolic or sex hormone levels and growth factors, decreased obesity and central adiposity, alterations in immune functions, and alternations in reactive oxygen species (ROS). Interestingly, different levels of exercise may influence the ROS generation in different ways. In fact, it has been suggested that moderate levels of exercise may have protective effects while too much exercise can be harmful. Thus, the determination of the optimal load of physical activity that can elicit cancer-preventive effects warrants further investigation. It is imperative to determine the best approach to keep prostate cancer at bay. Although much research still needs to be accomplished regarding the effect of micronutrients and macronutrients in prostate cancer progression, it is suggested that one can maintain overall good health by eating a well-balanced diet that is low in fat and carbohydrates, but rich in fruits and vegetables, and accompanied by moderate exercise. References 1. Chan, J. M., et.al. Role of diet in prostate cancer development and progression. J. Clin. Oncol. 23: pp 8152– 8160, 2005. 2. Fleshner, NE., et al. Dietary Fat and Prostate Cancer. The Journal of Urology.171 (2): pp S19-S24, 2004. 3. Venkateswaran, V., et al. Antioxidants block prostate cancer in Lady transgenic mice. Cancer Research. 64: pp 5891-5896, 2004. 4. Haddad, A., et al. Novel antiproliferative flavonoids induce cell cycle arrest in prostate cancer cell lines. Prostate Cancer Prostatic Diseases. 9 (1): pp 68-76, 2005. 5. Venkateswaran, V. Selenium and Prostate Cancer: Biological Pathways and Biochemical Nuances. Cancer Therapy. 4: pp 73-80, 2006. 6. Venkateswaran, V., et al. Early commencement of micronutrients is beneficial in reducing the incidence of prostate cancer and increasing survival in the Lady transgenic model. Cancer Prevention Research. 2 (5): pp 473-483, 2009. 7. Venier N., et al. Chemopreventative Strategies in Prostate Cancer: Role of Dietary Agents. Invited Review. Current Cancer Therapy Reviews. 6: pp 308-316, 2010. 8. Venkateswaran, V., et al. Diet and prostate cancer: mechanisms of action and implications for chemoprevention. Nature Reviews Urology. 7: pp 442-453, 2010. 9. Huang, H.Y., et al. Customized diets for cancer prevention according to genetic polymorphisms: are we ready yet? Journal of the National Cancer Institute. 98(22): 1590-1, 2006. 10. Venkateswaran, V., et al. Association of diet induced hyperinsulinemia with accelerated growth of prostate cancer (LNCaP) xenografts. Journal of the National Cancer Institute. 99: pp 1793-800, 2007. 11. Na, HK., et al. Effects of physical activity on cancer prevention. Ann. N.Y. Acad. Sci. Issue: Nutrition and Physical Activity in Aging, Obesity, and Cancer. 1229: 176–183, 2011. IMS MAGAZINE FALL 2011 PROSTATE CANCER | 18
Page 1: IMSMAGAZINE FALL THINK, LEARN, DISC
Page 4 and 5: COMMENTARY Tell us what you think
Page 6 and 7: NEWS AT A GLANCE NEWS&VIEWS OCTOBER
Page 9 and 10: DIRECTOR’S MESSAGE Director’s M
Page 11 and 12: IMS SURP HIGHLIGHT IMS SUMMER INTER
Page 13 and 14: IMS SURP HIGHLIGHT SURP Day Winners
Page 15 and 16: FEATURE The prostate is a walnut-s
Page 17: FEATURE analysis suggested a small
Page 21 and 22: FEATURE T ADC DCE MRI - K ep map Fi
Page 23 and 24: FEATURE Pick Your Brain... A column
Page 25 and 26: FEATURE I n line with this hope, it
Page 27 and 28: SPOTLIGHT itself as a versatile and
Page 29 and 30: CLOSE UP Dr. Jill Cameron many of t
Page 31 and 32: SURP RESEARCH FOCUS Given the rigou
Page 33 and 34: VIEWPOINT I think about the ablest
Page 35 and 36: VIEWPOINT this bias should be of hi
Page 37 and 38: BEHIND THE SCENES Most students kno
Page 39 and 40: FUTURE DIRECTIONS terest in genetic
Page 41 and 42: Ask Experts the Dear Experts, Last
Page 43 and 44: DIVERSIONS SUDOKU 2 7 1 5 8 4 9 6 2

Fall 2011 - Institute of Medical Science - University of Toronto

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?