America is becoming a heftier nation. Take three American adults, and current statistics show that one of them is likely to be overweight, and another one out of the three is frankly obese. The health consequences here are serious; some illnesses, such as diabetes, hypertension, and coronary artery disease, have long been linked to obesity. But it turns out that obesity plays a role in cancer, too. In 2003, a landmark study by the AmericanCancer Society showed that obese people are at increased risk for death from several kinds of cancer, including prostate cancer.

What does this mean for a man being diagnosed today, with early-stage diseas ethat is considered curable by surgery or radiation therapy? Did obesity somehow affec this development of prostate cancer — and more significantly, does it change his odds of surviving it? Hopkins investigators, led by urologist Stephen Freedland, M.D., have been trying to answer these questions, and they have made some important discoveries.

First, Freedland and his team noted that obese men treated by radical prostatectomy at several Veterans Affairs Hospitals were more likely to have their cancer come back after surgery. In two further studies, they have extended these findings to more than 5,000 men treated by radical prostatectomy at Johns Hopkins Hospital. “These studies provide strong evidence that obese men undergoing radical prostatectomy are more

likely to have aggressive prostate cancer,”says Freedland. However, he notes, the exact reason for the more aggressive cancers remains unclear.

One problem with studying obesity is simply defining the term “obese.” Men can be very muscular and weigh a lot without being obese. In addition, recent evidence suggests that obesity may lower levels of PSA in the blood — perhaps masking cancer when it is less aggressive.

Because both of these factors make it challenging to study how obesity affect sprostate cancer, Freedland and his team are also exploring potential molecular links that would explain why obese men may be at greater risk for aggressive cancer. For example, along with Alan Partin, M.D., David Hall McConnell Professor and Director of Urology, they examined the expression of two hormones made by fat cells: leptin and adiponectin. It turns out that obese men produce more leptin but less adiponectin in the blood than thinner men.

The scientists did not find any association between leptin and aggressive prostate cancer. However, they may have struck gold with adiponectin: Overweight and obese men who had lower adiponectin levels tended to have higher-grade cancers.

“Though the data for adiponectin look exciting, we continue to search for new molecular links between obesity and prostate cancer,” Freedland says. In exciting new research, Freedland, William Isaacs, Ph.D, the William Thomas Gerrard, Mario Anthony Duhon and Jennifer and John Chalsty Professor of Urology, and Jun Luo,Ph.D., assistant professor of urology, have begun to examine genetic differences in the cancers of men who are obese and men who are not. In their preliminary studies, they’ve found that cancers from obese men have a“molecular fingerprint,” and can be distinguished from cancers from trimmer men. They are currently investigating some ofthese genetic differences. Notes Freedland: “We hope that the differences we have found may give us some insight into why obesity causes more aggressive prostate cancer —which, in turn, will give us greater insight into prostate cancer biology in general.”