Population-Based Family History–Specific Risks for Colorectal Cancer: A Constellation Approach

David P. Taylor, Randall W. Burt, Marc S. Williams, Peter J. Haug, Lisa A. Cannon–Albright
2010 Gastroenterology  
BACKGROUND & AIMS: Colorectal cancer (CRC) risk estimates based on family history typically include only close relatives. We report familial relative risk (FRR) in probands with various combinations, or constellations, of affected relatives, extending to third-degree. METH-ODS: A population-based resource that includes a computerized genealogy linked to statewide cancer records was used to identify genetic relationships among CRC cases and their first-, second-, and third-degree relatives
more » ... SDRs, and TDRs). FRRs were estimated by comparing the observed number of affected persons with a particular family history constellation to the expected number, based on cohort-specific CRC rates. RESULTS: A total of 2,327,327 persons included in Ն3 generation family histories were analyzed; 10,556 had a diagnosis of CRC. The FRR for CRC in persons with Ն1 affected FDR ϭ 2.05 (95% CI, 1.96 -2.14), consistent with published estimates. In the absence of a positive first-degree family history, considering both affected SDRs and TDRs, only 1 constellation had an FRR estimate that was significantly Ͼ1.0 (0 affected FDRs, 1 affected SDR, 2 affected TDRs; FRR ϭ 1.33; 95% CI, 1.13-1.55). The FRR for persons with 1 affected FDR, 1 affected SDR, and 0 affected TDRs was 1.88 (95% CI, 1.59 -2.20), increasing to FRR ϭ 3.28 (95% CI, 2.44 -4.31) for probands with 1 affected FDR, 1 affected SDR, and Ն3 affected TDRs. CONCLUSIONS: Increased numbers of affected FDRs influences risk much more than affected SDRs or TDRs. However, when combined with a positive first-degree family history, a positive second-and third-degree family history can significantly increase risk.
doi:10.1053/j.gastro.2009.11.044 pmid:19932107 pmcid:PMC2831153 fatcat:fxnte5smt5esph2zoqfpwh3osi