Family history of colorectal cancer is not associated with colorectal cancer survival regardless of microsatellite instability status.

Phipps AI1, Ahnen DJ2, Campbell PT3, Win AK4, Jenkins MA5, Lindor NM6, Gryfe R7, Potter JD8, Newcomb PA9.

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Abstract

Background: Individuals with a family history of colorectal cancer (CRC) in first-degree relatives have an elevated risk of developing CRC themselves, particularly CRC exhibiting high microsatellite instability (MSI-high). Given that MSI-high CRC is associated with a favorable prognosis, it is plausible that having a family history of CRC could, in turn, be favorably associated with CRC survival. Methods: This study comprised N=4284 incident CRC cases enrolled in the Colon Cancer Family Registry via population-based cancer registries. Using Cox proportional hazards regression, we evaluated the association between family history and both overall and disease-specific survival, accounting for MSI status and tumor site via stratified analyses and statistical adjustment. Results: There was no evidence of association between family history and overall [hazard ratio (HR)=0.92, 95% confidence interval (CI): 0.79-1.08] or disease-specific survival (HR=1.03, 95% CI: 0.85-1.24) for all cases combined, after adjustment for MSI status or tumor site. Only for rectal cancer cases was CRC family history modestly associated with more favorable overall survival (HR=0.75, 95% CI: 0.56-0.99). Conclusions: Although individuals with a family history of CRC were more likely to have MSI-high tumors than those with non-familial disease, this did not translate to a survival benefit. Impact: Overall, there is no evidence that family history of CRC is associated with CRC survival; however, specific mechanisms underlying family history may have prognostic impact and merit further study.