BackgroundWhether the progression of precursor lesions or the occurrence of cancer is influenced by lifestyle factors in carriers of genetic mutations has not been fully investigated, especially in Asian patients of hereditary colorectal cancer (CRC) syndrome.MethodsPatients at a high risk of hereditary CRC were included. For polyposis CRC syndromes, colorectal polyp burden was measured using at least 60 images per colonoscopy in each patient and classified into five stages using the International Society for Gastrointestinal Hereditary Tumours staging system according to the polyp number and size. Increase in tumor burden stage for polyposis CRC syndrome and the occurrence of CRC or any cancer for Lynch syndrome were analyzed according to lifestyle factors.ResultsNinety‐six patients with suspected hereditary polyposis CRC syndrome and 106 patients with Lynch syndrome were recruited. For polyposis CRC syndromes, multivariate analysis showed that exposure to smoking and > 100 polyps independently predicted a high risk of increased polyp burden (p = 0.008 and p = 0.012, respectively). Significant genetic mutations or phenotype of polyposis syndromes were significantly associated with an increased polyp burden. For Lynch syndrome, smokers showed to be diagnosed with CRC in younger age than never‐smokers (42.2 years vs. 49.0 years; p = 0.021), and heavy drinkers had high risk for occurrence of CRC (HR, 2.381, 95% CI, 1.338–4.236; p = 0.003) and any cancer (HR, 2.254; 95% CI, 1.334–3.806; p = 0.002).ConclusionsThe lifestyle factors (smoking and alcohol consumption) were associated with increasing precursor lesions and occurrence of cancer in patients with hereditary CRC syndrome. Lifestyle modifications may reduce the risk of hereditary CRC in carriers.