Which inherited familial syndromes are listed as risk factors for colorectal cancer?

• A. BRCA1 and BRCA2
• B. Li-Fraumeni syndrome
• C. Peutz-Jeghers syndrome
• D. FAP and HNPCC

Answer: (D)

Inherited risk for colorectal cancer is driven by specific genetic syndromes that either cause numerous polyps or impair DNA repair, leading to early cancer development. The two classic high-risk conditions are familial adenomatous polyposis and Lynch syndrome. FAP comes from germline mutations in the APC gene, producing hundreds to thousands of polyps in the colon and rectum; without intervention, nearly everyone develops colorectal cancer, so intensive surveillance and often prophylactic colectomy are key management ideas. Lynch syndrome, caused by defects in mismatch repair genes, markedly increases colorectal cancer risk, often at a younger age, with cancers that can arise in the proximal colon and are associated with other cancers as well; regular, earlier, and more frequent colonoscopic screening is essential.

BRCA1/BRCA2 are mainly linked to breast and ovarian cancers, with colorectal cancer not serving as the primary inherited risk focus. Li-Fraumeni syndrome involves a broad cancer spectrum due to TP53 mutations, but colorectal cancer is not the defining elevated risk. Peutz-Jeghers does raise cancer risk, including colorectal cancer, but the strongest, most clearly recognized inherited colorectal cancer risk syndromes are the two listed—FAP and HNPCC.