Seven Cancer Types Proven to Be Associated with BRCA1 and BRCA2 Mutations

Previous studies have shown that breast, ovarian, prostate and pancreatic cancers are associated with BRCA1 and BRCA2. A new, large case-control study found that pathological variants (harmful mutations) in the BRCA1 and BRCA2 genes are associated with a broader range of cancer types. JAMA Oncology journal published findings suggesting that BRCA1 and BRCA2 genetic testing should be performed in a broader group of patients.

In addition to the previously known associations, this new study found that pathological mutations in BRCA1 were associated with biliary tract cancer, those in BRCA2 with esophageal cancer, and those in BRCA1/2 with stomach cancer as well.

NOTE: The name BRCA1 means "BReast CAncer 1  (Breast Cancer 1)", while BRCA2 means "BReast CAncer 2 (Breast Cancer 2)". The BRCA1 and BRCA2 genes, located on chromosome 17, play a role in cell growth, cell division and DNA damage repair. Mutations in BRCA genes may cause DNA damage to accumulate in cells without being repaired, increasing a person's likelihood of developing certain cancer types. The presence of BRCA mutations in a patient makes that person more sensitive to RAPR inhibitors , a new class of cancer drugs.

The Japanese Study

The team led by Dr. Yukihide Momozawa at the Center for Integrative Medical Sciences in Japan wrote the following about their new study:

“We found that the range of cancer types associated with pathological variants (mutations) in BRCA1 and BRCA2 was broader than identified in previous analyses of European studies. Our analysis is relevant to developing and harmonizing guidelines on genetic testing, treatment options and treatability with PARP inhibitors for each cancer type.”

Momozawa and colleagues conducted large-scale genetic sequencing for 14 common cancer types using data from 63,828 patients and 37,086 controls obtained from a Japanese biobank between April 2003 and March 2018. The study estimated the risk for each cancer type and identified clinical features associated with pathogenic variant carrier status. They also investigated the usefulness of family history in identifying patients with pathogenic variants.

315 Pathological Variants Identified (the total number of harmful genetic changes in the 2 genes)

Risk ratios were quite high for biliary tract cancer with BRCA1, esophageal cancer with BRCA2, and stomach cancer with BRCA1 and BRCA2. An additional 2 cancer types associated with BRCA1 and 4 associated with BRCA2 were found. Consistent with an increasing number of cancer types reported in relatives, the number of carrier patients increased for biliary tract, female breast, ovarian and prostate cancers.

Male patients with breast cancer had a particularly high frequency of pathological variants in BRCA2 (18.9%), but not in BRCA1 (1.89%). Patients with ovarian cancer had the next highest frequency (4.6% for BRCA1 and 3.42% for BRCA2). Frequencies exceeding 1% were seen in the other six cancer types with newly observed associations. More than one cancer type was identified in 4,128 patients (6.3%). The frequency of carrying pathological variants in BRCA1 was 0.44% for one cancer type, 0.85% for two cancer types and 0.69% for three cancer types. These rates were 0.97%, 1.40% and 1.74% for BRCA2, respectively.

Genetic Testing for BRCA1 and BRCA2 Mutations Should Be Used More Widely

The new generation of cancer drugs called PARP inhibitors was developed to target pathological mutations in DNA repair genes. PARP inhibitors had so far shown significant efficacy in ovarian, breast, prostate and pancreatic cancers with pathogenic BRCA1 and BRCA2 variants. This new study highlights the importance of testing more patients for hereditary cancer genes, potentially allowing PARP inhibitor drugs to benefit more patients. These tests should be considered particularly for patients with a family history of cancer who have biliary tract cancer, cervical cancer, colon and rectal cancer, endometrial cancer, esophageal cancer or stomach cancer.

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• Related topic: Should All Cancer Patients Have Hereditary Genetic Testing?