BRCA Mutations a Risk for Pancreatic and Prostate Cancers

Dr Rob Hicks

January 27, 2022

The researchers of a study, published in the Journal of Clinical Oncology , have assessed the risks associated with BRCA1 and BRCA2 mutations and primary cancers other than female breast and ovarian cancers, since it is already well established that faulty versions of BRCA1 and BRCA2 are linked to increased risk of these cancers.

The authors emphasise that "being able to estimate the risks accurately is important for informing cancer prevention and screening strategies and providing genetic counselling to those at greatest risk".

For their study the researchers from the University of Cambridge used data from 26 study groups in the Consortium of Investigators of Modifiers of BRCA1/2, which included 7,618 families with at least one family member having a BRCA1 or BRCA2 mutation. All individuals were at least 18 years old.

The researchers then analysed data from 3,184 families with one or more members with the BRCA1 mutation and 2157 families with members carrying the BRCA2 mutation, examining the associations with 22 primary cancers.

Links Between Cancer and BRCA1 and BRCA2 Much Clearer

Prof Antonis Antoniou from the Department of Public Health and Primary Care at the University of Cambridge, who led the research, said: "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. We’ve known for some time that they’re linked to breast and ovarian cancer, but there’s been uncertainty about other cancers."

The researchers estimated that by the time they are 80 years old, men who carry a BRCA2 mutation have a 27% risk of developing prostate cancer, more than double the rate of non-carriers. However, they found that BRCA1 mutations were not associated with an increase in prostate cancer risk.

For those with a faulty copy of either BRCA1 or BRCA2 the risk of developing pancreatic cancer by age 80 was double (2.5% to 3.0%) that of non-carriers.

The BRCA1 and BRCA2 mutations were also found to increase the risk of stomach cancer, though the researchers caution that because of the rarity of this form of cancer, the number of patients in their datasets was small.

Mutations in both genes significantly increased the risk of breast cancer in men - BRCA1 mutation increased the risk more than fourfold to 0.4% by age 80, a BRCA2 mutation increased the risk by 44 times to 3.8% by age 80.

The researchers said they were "unable to find compelling evidence that mutations were linked to increased risk of some other cancers which were previously thought to be linked to faulty BRCA genes, such as melanoma".

Prof Marc Tischkowitz from the Department of Medical Genetics at the University of Cambridge said: "The link between BRCA2 and prostate cancer and pancreatic cancer is now much clearer, thanks to the data we’ve analysed. We have also identified a potential link with stomach cancer, but this is based on small numbers and needs further study.” He added that their data suggests that there is “no strong link between BRCA2 and melanoma, which may provide greater clarity to BRCA2 gene carriers."

Optimise Screening and Early Detection Strategies

Michelle Mitchell, chief executive of Cancer Research UK, who funded the study, said: "Cancers caused by inherited faulty BRCA genes are relatively rare, and other factors like age, smoking, diet and other preventable factors contribute to a person’s risk."

Prof Tischkowitz emphasised: "Overall, the results will add to our knowledge on optimising cancer screening and early detection strategies for people who are known to carry these faulty genes."

Michelle Mitchell added that: "Improving our understanding of how faults in our genes are associated with certain cancers puts us in a much better position to pinpoint those at a higher risk of developing cancer."

The authors concluded their study results and estimated age-specific risks will "improve the cancer risk management for men and women" with BRCA1 and BRCA2 mutations.

Li S, Silvestri V, Leslie G, et al. Cancer risks associated with BRCA1 and BRCA2 pathogenic variants. J Clin Oncol. Published online January 25, 2022. PMID: 35077220. DOI: 10.1200/JCO.21.02112

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