From the Desk of the Editor: Obesity is Linked to High-Grade Prostate Cancer

Obesity is all around us.  Over 30% of all Americans are obese. We know obesity is linked with many medical problems – heart disease, diabetes, hypertension, and of course cancer. Indeed, over a dozen different cancers have been linked with obesity. In regards to prostate cancer, while obesity may lower the risk of low-grade indolent cancer, it unequivocally increases the risk of high-grade aggressive disease. Many explanations have been put forward: alterations in insulin levels, changes in sex steroid hormone levels, higher cholesterol, and higher systemic inflammation. More recent data suggest that the fat cells themselves secrete hormones (leptin and adiponectin) that may influence prostate cancer growth. However, new data from Gucalp et al. suggest that the degree of inflammation in the fat may also contribute to aggressive prostate cancer.

Building upon their experience with breast cancer, Gucalp examined the adipose tissue right next to the prostate (periprostatic adipose tissue) obtained at the time of radical prostatectomy. The adipose tissue was stained with CD68, a general marker of macrophages, and assessed for crown-like structures. This is essentially a collection of macrophages around the fat cells.  If this was found, the patient was considered to have periprostatic adipose tissue inflammation. Among the 169 men examined, nearly half had periprostatic adipose tissue inflammation. Those with the inflammation were more likely to be younger, heavier, and importantly have high-grade disease. These patients also tended to have other lab tests consistent with obesity – higher leptin, lower adiponectin, higher insulin and triglycerides, and lower HDL, consistent with a generalize metabolic syndrome. Even when adjusting for body weight, inflammation was linked with high-grade disease, suggesting it is independent of the link with body weight.

Like any good study, this one by Gucalp raises more questions than it answers.  How is inflammation in fat cells linked with aggressive prostate cancer?  Do inflamed fat cells release products that promote prostate cancer aggressiveness?  Is the signal coming from the inflammatory cells?  Alternatively, is it the cancer that is giving off signals that lead to inflammation?  If so – why is it seen in the fat?  If you measured fat farther away from the prostate – would you see the same results?  Ultimately, what can we do about this? Will anti-inflammatory drugs reduce this?  Weight loss?  Exercise? 

Ultimately, this study provides yet more data to support the fact that there is a strong link between obesity, fat, and prostate cancer with inflammation a likely key mediator, though it is certainly not the sole mediator. We look forward to furthering data from this group and others to move from interesting observations to better mechanistic understanding to ultimately interventions to negate these effects.

Written by: Stephen Freedland, MD Editor-in-Chief, Prostate Cancer and Prostatic Diseases Cedars-Sinai Medical Center, Los Angeles, CA

Read the PCAN Full-Text Article