BRCA1/2 pathogenic variants linked to prostate, pancreatic and stomach cancers

Reuters Health - 31/01/2022 - Mutations in the BRCA1 and BRCA2 genes that increase the risk of breast cancer also raise the risk of prostate and pancreatic cancer, new research confirms.

"The link between BRCA2 and prostate cancer and pancreatic cancer is now much clearer, thanks to the data we've analyzed," Dr. Marc Tischkowitz of the University of Cambridge, UK, said in a news release.

The study also uncovered a potential increased risk of stomach cancer with BRCA1/2 mutations, but this is based on small numbers and needs further study, the researchers caution.

They analyzed health record data from 3,184 families with the BRCA1 mutation and 2,157 families with the BRCA2 mutation participating in the Consortium of Investigator of Modifiers of BRCA1/2. They evaluated the association of BRCA1/2 mutations with 22 primary cancers (other than female breast and ovarian 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. We've known for some time that they're linked to breast and ovarian cancer, but there's been uncertainty about other cancers," senior author Dr. Antonis Antoniou, also at Cambridge, said in the news release.

The two researchers and their colleagues found that BRCA1 mutations were associated with an increased risk of male breast cancer (relative risk, 4.30; 95% CI, 1.09 to 16.96), pancreatic cancer (RR, 2.36; 95% CI, 1.51 to 3.68) and stomach cancer (RR, 2.17; 95% CI, 1.25 to 3.77).

BRCA2 mutations were associated with increased risk of male breast (RR, 44.0; 95% CI, 21.3 to 90.9), stomach cancer (RR, 3.69; 95% CI, 2.40 to 5.67), pancreatic cancer (RR, 3.34; 95% CI, 2.21 to 5.06), and prostate cancer (RR, 2.22; 95% CI, 1.63 to 3.03).

The relative risk increase of stomach cancer was higher for women than men (6.89 v 2.76; P=0.04).

"The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers," the study team reports in the Journal of Clinical Oncology.

They note that previously suggested associations of BRCA1/2 mutations with risks of other genitourinary cancers and melanoma were not replicated. Although associations of BRCA1 mutations with colorectal and gallbladder cancers were observed, the results were not robust in the sensitivity analyses.

No associations were found with risks of other cancers.

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

Michelle Mitchell, Chief Executive of Cancer Research UK, said in the press release, "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. 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 study was supported in part by grants from Cancer Research UK.

SOURCE: https://bit.ly/3rdwBq8 Journal of Clinical Oncology, online January 25, 2022.

By Reuters Staff



Posted on 31 January 20228 February 2022