Cancer Genetics
Hereditary cancer fundamentals
Know the hallmarks that raise suspicion of a hereditary syndrome: early age at diagnosis, multiple primaries, bilateral or multifocal disease, male breast cancer, ovarian cancer, Ashkenazi Jewish ancestry for BRCA, and clustering of related cancers across generations. Understand that hereditary cancer syndromes are often autosomal dominant with incomplete penetrance, so an unaffected carrier remains at elevated risk.
Genes and management concepts
Candidates should recognize the broad roles of high-penetrance genes such as BRCA1 and BRCA2 (breast and ovarian cancer), mismatch repair genes (Lynch syndrome, colorectal and endometrial cancer), and TP53 (Li-Fraumeni). Management discussions involve enhanced surveillance, risk-reducing surgery, and chemoprevention, always framed as shared decisions with the client's team. Exact risk figures vary by gene, mutation location, and family history; avoid quoting a single number as universal.
Traps
Frequent errors: assuming a negative family history excludes a syndrome (small families and paternal transmission hide patterns); treating a variant of uncertain significance as actionable for surgery; forgetting that a BRCA2 result also carries pancreatic and prostate cancer implications; and confusing somatic tumor testing with germline testing. Tumor profiling may reveal germline findings and should prompt referral when suspicion exists.
Worked example
A 42-year-old woman with triple-negative breast cancer has no family history. Age and subtype raise suspicion despite the negative history. Genetic testing is offered; if a pathogenic BRCA1 variant is found, her relatives each face a 50% chance of carrying it, and cascade testing is arranged. Rule of thumb: test the affected person first whenever possible, because it yields the most informative result.