Cancer risk for male and female carriers of BRCA1/2 mutations

It is well known that female carriers of the BRCA1 and BRCA2 gene mutations have increased risk of cancers, but new research published in the Journal of Clinical Oncology reveals an increased risk of various cancers for male carriers as well.

The research team from The University of Melbourne, the University of Cambridge and Sapienza University of Rome claims to have used the largest sample size ever in a cancer study of the same kind worldwide, using the data of 3184 BRCA1 families and 2157 BRCA2 families (with at least one family member having a mutation) across 26 studies from 18 countries. The families included 14,979 carriers, 9296 non-carriers and 153,323 untested individuals.

The study established that in addition to female breast and ovarian cancers, BRCA1/2 carriers are at risk for male breast, pancreatic, stomach and prostate (BRCA2 carriers only) cancers, but not other cancers as previously thought. Significantly, the study team found that BRCA1/2 carriers did not have higher risk of melanoma.

Senior author Professor Antonis Antoniou, from the University of Cambridge, said it had been known for some time that the gene mutations were linked to breast and ovarian cancer, but there had been uncertainty about other cancers.

“These large datasets of patients have allowed us to estimate with much greater accuracy the extent to which faulty BRCA1 and BRCA2 genes increase the risk of several cancers,” Prof Antoniou said. “At the same time, the findings will be reassuring because they show that many other cancers are not linked to the BRCA1 and BRCA2 genes.”

The research is said to provide the most up-to-date evidence and precise cancer risks for BRCA1 or BRCA2 mutation carriers, with the findings expected to change guidelines on clinical management of BRCA1/2 mutation carriers. Indeed, lead author Dr Shuai Li, from the University of Melbourne, suggested that male relatives of known BRCA1/2 carriers should be informed about their individual cancer risk.

“They should be informed about cancer risk and encouraged to be tested, because male and female carriers have the same cancer risks for pancreatic and stomach cancers, and male BRCA2 carriers also have increased risk of prostate cancers,” said Dr Li, a Victorian Cancer Agency Early Career Research Fellow. “Male carriers can also have increased risk of developing breast cancer. BRCA-related cancers are not a ‘female only’ thing.”

Dr Li said while rare, incidences of pancreatic and stomach cancers are rising, and because they are difficult to detect and have low survival rates, the study showed how important it is to screen for upper gastrointestinal tract malignancies in carriers, particularly for those under 65 years of age.

The research team now plan to use prospectively collected data of BRCA1/2 carriers to further refine the findings, using the same method to investigate the cancer risks of carriers of other genes, such as ATM, CHEK2 and TP53.

Image credit: ©stock.adobe.com/au/Antonio Tanaka

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