Genetic Mutation May Play a Role in Worse Outcomes for Obese Prostate Cancer Patients
A study by researchers from Harvard School of Public Health, Dana-Farber Cancer Institute, and Brigham and Women’s Hospital has found that overweight or obese men with prostate cancer whose tumors were positive for the TMPRSS2:ERG genetic mutation had more than a 50% increased risk of dying from cancer after their diagnosis compared with normal-weight men. There was no effect of obesity on cancer survival among men whose tumors did not have the mutation. The study by Pettersson et al is published in the Journal of the National Cancer Institute.
Study Details
The study included 1,243 participants in the Physicians’ Health Study and Health Professionals Follow-up Study who were diagnosed with prostate cancer between 1982 and 2005. During a follow-up period averaging 13 years, 119 men developed a lethal form of the disease (23 men developed distant metastases and 96 men died of prostate cancer).
ERG overexpression (a TMPRSS2:ERG marker) was assessed by immunohistochemistry of tumor tissue collected from radical prostatectomy or transurethral resection of the prostate. The men provided weight and height information in 1982, then weight again at 8 years follow-up and annually thereafter. Waist circumference was provided at 9 years' follow-up.
Findings
The researchers found that one in two men with prostate cancer had tumors that were positive for the TMPRSS2:ERG mutation. Among the men with prostate cancer whose tumors had the mutation, those who were overweight or obese had a more than 50% increased risk of dying from cancer after their diagnosis compared with normal-weight men. In addition, among both all men and men with ERG-positive tumors, waist circumference increased the risk of lethal prostate more than BMI (body mass index) before diagnosis did.
Obesity is associated with higher levels of several hormones, including insulin and growth factors that may fuel the progression of cancer. According to the study findings, men whose tumors contained the TMPRSS2:ERG genetic mutation also had higher levels of the receptors for insulin and growth factor in their tumors. The results may explain why men whose prostate tumors contain the genetic mutation would be more susceptible to the effects of obesity.
“The results from this study may help us better understand the mechanisms linking obesity with poorer prostate cancer prognosis,” said Andreas Pettersson, MD, PhD, visiting scholar in the Harvard School of Public Health Department of Epidemiology, in a statement. “The key public health message is unchanged, however. Prostate cancer patients who are overweight or obese should lose weight to increase their chance of survival, regardless of whether their tumors carry this genetic change or not.”
If the study findings are confirmed, they could advance the understanding of the molecular factors linking obesity and prostate cancer outcome and potentially inform prostate cancer therapy development and secondary prevention strategies, concluded the authors.
Lorelei A. Mucci, ScD, of Harvard School of Public Health, is corresponding author of the Journal of the National Cancer Institute article.
Funding was provided by the Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence program in prostate cancer; the National Cancer Institute; the National Heart, Lung, and Blood Institute; the Prostate Cancer Foundation; the Swedish Research Council; and the Royal Physiographic Society in Lund.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
