Background: Colorectal cancer survivors have increased risks of subsequent primary cancers (SPCs), but most studies have included individuals with hereditary colorectal cancer syndromes. This study assessed SPC risks for colorectal cancer survivors without a known hereditary predisposition to colorectal cancer.
Methods: We analyzed data from the Colon Cancer Family Registry Cohort, recruiting participants between 1998 and 2012 through population cancer registries in Australia, Canada and the United States, with follow-up every five years (until December 2022). Individuals with pathogenic germline mutations in APC, MUTYH, or DNA mismatch repair genes were excluded. Standardized incidence ratios (SIRs) were calculated by comparing observed cases with expected cases based on age-, sex-, country-, and calendar period-specific incidence rates.
Findings: The study included 7202 (49.8% female) colorectal cancer survivors with a mean age at diagnosis of 55.1 (SD 11.5) years and a mean follow-up of 10.6 (SD 7.45) years. Overall, there was no evidence of increased SPC risk (SIR 1.04, 95% CI: 0.98-1.11). Elevated risks were observed for subsequent primary colorectal (SIR 1.34, 95% CI: 1.14-1.57), hematopoietic (SIR 2.49, 95% CI: 1.92-3.21), liver (SIR 2.25, 95% CI: 1.51-3.36), and thyroid (SIR 1.90, 95% CI: 1.20-3.02) cancer. Early-onset colorectal cancer cases (diagnosed before age 50) had increased SPC risks (SIR 1.43, 95% CI: 1.25-1.64) while those diagnosed at 50 and above did not (p < 0.001).
Interpretation: In non-hereditary colorectal cancer survivors, overall SPC risks are not elevated, but early-onset cases have higher risks and therefore warrant targeted surveillance and follow-up.
Funding: National Institutes of Health (U01 CA167551) and National Health and Medical Research Council (1194392).
