BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to be associated with the occurrence of solid tumors, but its relationship with colorectal cancer still needs to be studied. METHODS: We conducted a prospective matched case-control study using data from the UK Biobank, including 5,310 incident colorectal cancer cases and 26,550 controls matched for age, sex, and body mass index. RESULTS: Analysis of the UK Biobank data revealed that the presence of CHIP was associated with an increased risk of colorectal cancer. The odds ratio (OR) for colorectal cancer in the presence of CHIP was 1.20 (P = 0.006). This association remained significant even after excluding participants with a family history of bowel cancer (multivariate OR, 1.19
P = 0.007). Subgroup analyses demonstrated that CHIP independently increased the risk of colorectal cancer in females (multivariate OR, 1.25
P = 0.018) and in individuals older than 60 years (multivariate OR, 1.17
P = 0.046). Gene-specific analyses revealed that mutations in TET2 and ATM were particularly significant in relation to colorectal cancer risk, with an OR of 1.62 (P = 0.002) for TET2 and 2.98 (P <
0.002) for ATM. CONCLUSIONS: Our findings indicate that CHIP is associated with an increased risk of colorectal cancer, particularly in individuals more than 60 years of age or in females. IMPACT: Screening for CHIP in the population may improve the early detection and diagnosis rates of colorectal cancer.