Which genes are considered indicators of hereditary cancer susceptibility in breast cancer risk assessment?

• A. BRCA1 and BRCA2
• B. TP53 and PTEN
• C. KRAS and BRAF
• D. MSH2 and MLH1

Answer: (A)

High-penetrance hereditary breast cancer risk is most clearly indicated by germline mutations in BRCA1 and BRCA2. These genes code proteins that repair double-strand DNA breaks through homologous recombination; when they’re dysfunctional, cells accumulate DNA damage and cancer risk rises substantially. The inheritance is autosomal dominant, so a parent with a pathogenic variant can pass it to about half of their children, making BRCA1/BRCA2 testing a central part of risk assessment for families with strong breast cancer histories or early-onset disease. A positive result guides intensified screening (earlier and more frequent MRI and mammography), consideration of risk-reducing options (like prophylactic surgeries), and informs relatives who may also carry the mutation.

Other genes listed are associated with cancer predisposition but are not the primary indicators used in standard breast cancer risk assessment. For example, TP53 and PTEN relate to broader syndromes with multiple cancer types; while they can increase breast cancer risk, they’re less central for routine breast cancer risk evaluation. KRAS and BRAF are commonly involved in tumor signaling pathways across various cancers, and MSH2/MLH1 are classic mismatch repair genes linked to Lynch syndrome, mainly colorectal and related cancers.