BRCA2 Mutations Have Stronger Link to Cancer in Men Than Do BRCA1 Mutations

By David Douglas

July 16, 2020

NEW YORK (Reuters Health) - Compared with men with germline BRCA1 pathogenic variants (PVs), those with BRCA2 PVs are more likely to be affected by cancer, according to a new study.

The research "fills a knowledge gap on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants," Dr. Laura Ottini of Sapienza University of Rome told Reuters Health by email.

"Our results, derived from analyses of the largest available male BRCA1/2 PV carrier data set, show that being affected by any cancer and developing multiple cancers, particularly breast, prostate and pancreatic cancers, is associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier," she said.

Dr. Ottini and colleagues examined data on more than 6,900 men, of whom 3,651 were BRCA1 and 3,251 BRCA2 PV carriers. They were recruited by study groups worldwide from cancer genetic clinics between 1966 and 2017, and their median age was 51.6 years.

Nearly 20% had at least one cancer diagnosis, the researchers report in JAMA Oncology. BRCA2 PV carriers were significantly more likely to be affected by any cancer (odds ratio, 3.23) and to have more than one primary tumor.

BRCA2 PV carriers were at greater risk of developing breast cancer (OR, 5.47) prostate cancer (OR, 1.39), and pancreatic cancer (OR, 3.00). However, they had a significantly lower probability of colorectal cancer (OR, 0.47).

"These data will help to optimize medical care in male BRCA1 and BRCA2 PV carriers," Dr. Ottini said. "In particular, screening and surveillance programs in men with BRCA1 and BRCA2 PVs should be tailored in light of these gene-specific cancer phenotype differences."

"Overall," she concluded, "this study will help oncologists to sensitize men with BRCA PVs in the perception of their personal cancer risk, and no longer only of their female relatives. Furthermore, these data will guide further studies, which we are working on, in order to develop increasing personalized and gender-specific guidelines to guarantee a better clinical management for all patients."

SOURCE: JAMA Oncology, online July 2, 2020.