Fat's fatal link to prostate cancer

Obesity is associated with an 80 percent increase in the risk of high-grade, aggressive prostate cancer, according to the largest and most comprehensive analysis to date on obesity and prostate-cancer risk.

Dr. Alan Kristal and colleagues in the Public Health Sciences Division conducted the analysis based on data from the nationwide Prostate Cancer Prevention Trial — a randomized, controlled clinical trial designed to look at the ability of the well-known baldness drug, finasteride, to prevent prostate cancer.

The study, published in the October issue of Cancer Epidemiology, Biomarkers and Prevention, showed that among men who had a first-degree relative with prostate cancer, the distribution of body fat also contributed to increased prostate-cancer risk. Such "apple-shaped" men, who stored fat in the abdominal area, were found to have a nearly twofold increased risk of both low- and high-grade prostate cancer.

The researchers found an increased risk of low-grade prostate cancer among the tallest men in the study — a finding that confirms previous research. "The correlation between height and prostate cancer probably has to do with the role of steroid hormones such as testosterone and estrogen that regulate both prostate development and height," Kristal said.

Interestingly, the study also found that obesity is linked to an 18 percent reduced risk of low-grade, non-aggressive prostate cancer, which accounts for about 80 percent of all cases. "This difference in the effect of obesity on low- and high-grade cancer answers a perplexing enigma about prostate cancer," Kristal said. "It helps explain why obese men are more likely to die of prostate cancer, as they are much more likely to get the form of prostate cancer that is difficult to treat and is often fatal."

Factor inflammation, hormones

Researchers believe the mechanisms behind the link between obesity and the most aggressive, fatal form of prostate cancer involve both steroid hormones and systemic inflammation. "Obesity is a massive inflammatory condition," Kristal said. "It also increases levels of circulating estrogens and growth factors that promote cell growth." While previous studies have examined the link between obesity and prostate-cancer risk, the results have been inconsistent.

This National Cancer Institute-funded study involved more than 10,000 participants, approximately one-fifth of whom developed prostate cancer. Strengths of the study include the fact that all of the men were screened for prostate cancer based on PSA level, digital-rectal exam and biopsy. In addition, a central pathology laboratory conducted all of the tissue analysis to ensure consistent interpretation of cancer grade. Trained staff collected measurements such as height and weight as opposed to relying on participants' self-reports.