Risk of Colorectal Cancer Associated With Frequency of Colorectal Polyp Diagnosis in Relatives

Background & Aims: The aim of the study was to evaluate the association of frequency of polyp diagnosis in relatives with the risk of overall and early-onset colorectal cancer (CRC). Methods: Data from nationwide Swedish family cancer datasets (1964–2018) were leveraged to calculate standardized incidence ratios for individuals with a family history of polyp by frequency of polyp diagnosis in family members. Results: A total of 11,676,043 individuals were followed for up to 54 years. Compared with the risk in individuals without a family history of colorectal tumor (n = 142,234), the risk of overall CRC was 1.4-fold in those with 1 first-degree relative (FDR) with 1-time polyp diagnosis (95% CI, 1.3–1.4; n = 11,035; early-onset standardized incidence ratio [SIR], 1.4; 95% CI, 1.3–1.5; n = 742). The risk was significantly higher in individuals with 1 FDR with 2 or more (frequent) polyp diagnoses (overall CRC: SIR, 1.8; 95% CI, 1.8–1.9; early-onset CRC: SIR, 2.3; 95% CI, 2.0–2.6). A rather similar risk was observed for individuals with ≥2 FDRs with 1-time polyp diagnosis (overall CRC: SIR, 1.9; 95% CI, 1.7–2.1; early-onset CRC: SIR, 2.2; 95% CI, 1.5–2.9). Individuals with ≥2 FDRs with frequent polyp diagnoses had a 2.4-fold overall risk (95% CI, 2.2–2.7) and a 3.9-fold early-onset risk (95% CI, 2.8–5.3). Younger age at polyp diagnosis in FDRs was associated with an increased risk of CRC. A family history of polyp in second-degree relatives was important only when there were frequent diagnoses of polyp. Conclusions: A higher frequency of colorectal polyp diagnosis in relatives is associated with a greater risk of CRC, especially early-onset CRC. This risk is independent of number of affected relatives or youngest age at polyp diagnosis. These findings underscore the need for more personalized CRC screening strategies that are tailored to individuals with a family history of polyp.