AUA: Prostate Cancer Studies Highlight DNA Repair Gene Involvement

Two new studies presented at the Annual Scientific Meeting of the American Urological Association (AUA) offer an improved understanding of some genetic underpinnings of prostate cancer. In one, researchers found that BRCA mutations may raise the risk of the malignancy substantially, while another found a high rate of mutations among other DNA repair genes as well.

“These studies reveal new insights into the role genetic mutations play in the development of prostate cancer, particularly metastatic disease,” said Scott Eggener, MD, of the University of Chicago Medicine, who moderated the session with these studies, in a press release.

One study focused on male carriers of BRCA genes; previous work has shown increased risk for various cancers, but there are currently no screening guidelines for this population of men. The study was presented by Roy Mano, MD, of Rabin Medical Center in Petah Tikva, Israel.

The study included 154 men known to be BRCA mutation carriers; 92 of them (60%) had BRCA1 mutations, 61 (40%) had BRCA2 mutations, and 1 had a mutation in both genes. Twenty-four participants (16%) were diagnosed with cancer upon enrollment or during initial screening, and they had a median age at diagnosis of 55 years.

Four patients had multiple malignancies; seven patients (8%) had prostate cancer with a BRCA1 mutation, and three (5%) had prostate cancer with a BRCA2 mutation. The researchers noted that these rates appear substantially higher than in the general population for this age group; also, these results suggest that prostate cancer risk may not be restricted to BRCA2 mutation carriers, as previous work has shown.

In the other study, presented by Allison Glass, MD, of the University of California, Davis, researchers analyzed samples from 936 localized and metastatic prostate cancers to study the distribution of DNA repair gene mutations.

Of the full cohort, 228 samples (24.4%) showed at least one likely functional mutation of a DNA repair gene. Those mutations were found in 20.1% of prostate tumors, and in 18.8% of bone metastases, and the highest rates of DNA repair mutations were seen in visceral metastases including brain, pelvis, and liver.

The genes most commonly mutated included BRCA2 (11% of samples), ATM (6.6%), MSH6 (2.5%), MSH2 (2%), ATR (1.6%), MLH1 (1.3%), and BRCA1 (1.2%). The authors noted that genomic profiling could potentially identify prostate cancer patients that are sensitive to platinum-based chemotherapy or to PARP inhibition.

“For some patients, a detailed understanding of these mutations could have a meaningful impact on the timely diagnosis and treatment of their disease,” Eggener said.