Why is it that obese men are more likely to develop aggressive prostate cancer, and to die of it? "One possible biological mechanism that underlies the association between obesity and prostate cancer is telomere shortening," says epidemiologist Corinne Joshu, Ph.D., M.P.H.. Telomeres are like aglets on shoelaces – little tips that protect the ends, except these tips are repetitive DNA sequences, and what they’re protecting from wear and tear are the ends of chromosomes. "Short telomeres can cause the chromosome to become unstable, and this abnormality is strongly associated with cancer" says telomere biologist Alan Meeker, Ph.D.
Joshu, Meeker, and colleagues including Christopher Heaphy, Ph.D., and Elizabeth Platz, Sc.D., M.P.H., have been investigating telomeres as part of a larger look at how obesity influences prostate cancer development and progression, with the hope of developing new strategies for treating the disease – and ideally, for preventing it. A previous study, led by Meeker and Platz in collaboration with colleagues at Harvard University, found that men with shorter telomeres in prostate cells near their tumor, called "prostate cancer-associated stromal cells," had a higher risk of dying from prostate cancer.
Next, the team investigated the association between obesity and telomere length in these prostate cancer-associated stromal cells. In a study of nearly 600 men who had undergone surgery to treat prostate cancer, "we found that men who were overweight or obese had telomeres that were 7.5 percent shorter in their cancer-associated stromal cells than those in men of normal weight," says Joshu. Even more striking: Men who were overweight or obese who were the least physically active had significantly shorter – by more than 20 percent – telomeres compared to men of normal weight who were the most active. "These findings not only suggest that telomere shortening in prostate cells is associated with obesity and low physical activity levels," says Joshu, "but it also may be one mechanism through which lifestyle influences prostate cancer risk and outcomes."
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"Our work on telomeres and prostate cancer will be helped tremendously by the recent acquisition of a state-of-the-art, automated fluorescence microscopy slide scanner, which was funded by the generous contribution of the donors," says Platz. This new equipment, Meeker adds, "will dramatically accelerate our telomere-based research on tissues, and will also open up new research avenues such as protein biomarker studies."