Pathogenic variants (disease-causing) in the APC gene cause familial adenomatous polyposis (FAP) and attenuated FAP, conditions marked by tens to thousands of colorectal polyps (polyposis) and a high lifetime risk of colorectal cancer if not managed. APC variants can also increase risks for duodenal (small bowel)/upper gastrointestinal polyps and cancer, desmoid tumors (benign but problematic tumors), and, less commonly, thyroid cancer and hepatoblastoma (primarily in young children). Management involves increases screening for polyps and tumors starting a younger age with routine surveillance.
In addition, there is a specific variant in the APC gene called I1307K that is seen more commonly in the Askenazi Jewish population, with about 6–10% carrying this variant. The APC I1307K variant increases colorectal cancer risk by 2-3 fold but typically does not cause polyposis or other FAP-related tumors.
Pathogenic variants in APC exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
