Familial colorectal cancer risk may be lower than previously thought: a Danish cohort study

Background: The risk of colorectal cancer (CRC) is reportedly increased two-fold if at least one first-degree relative (FDR) is affected with CRC, increasing to three- to four-fold if multiple FDRs are affected or if one FDR was diagnosed at a young age. We evaluated familial risk of CRC, systematically excluding monogenetic high-risk families with polyposis or Lynch syndrome/hereditary non-polyposis colorectal cancer (HNPCC).

Methods: FDRs of 1196 Danish CRC patients diagnosed between 1995 and 1998 (baseline) were identified and the family history of cancer was assessed at baseline using Danish medical registries; 4182 FDRs without CRC from 1060 of the families were matched on age and gender with ten individuals from the general population and followed from baseline to 2010. Family history was updated with any new cancer event during follow-up.

Results: Using Cox proportional hazard modeling the risk estimates were: at least one relative with CRC: hazard ratio (HR)=1.78 (95%CI: 1.45, 2.17), one relative with CRC diagnosed after the age of 50: HR=1.68 (95%CI: 1.32, 2.14), one relative with CRC diagnosed before the age of 50: HR=1.86 (95%CI: 0.70, 4.94), and multiple affected relatives: HR=2.04 (95%CI: 1.38, 3.00).

Conclusion: Although the overall risk in FDRs of CRC patients in our study was comparable with the results of previous studies, the risk in families with multiple relatives with CRC or one CRC patient diagnosed young may be lower than reported previously.