Population-Based Family History–Specific Risks for Colorectal Cancer: A Constellation Approach
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.
Methods
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 (FDRs, 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 ≥3 generation family histories were analyzed; 10,556 had a diagnosis of CRC. The FRR for CRC in persons with ≥1 affected FDR = 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 >1.0 (0 affected FDRs, 1 affected SDR, 2 affected TDRs; FRR = 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 = 3.28 (95% CI, 2.44–4.31) for probands with 1 affected FDR, 1 affected SDR, and ≥3 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.
Keywords: Colorectal, Relative Risk, UPDB
Abbreviations used in this paper: CRC, colorectal cancer, E, expected, FDR, first-degree relative, FRR, familial relative risk, O, observed, SDR, second-degree relative, TDR, third-degree relative, UCR, Utah Cancer Registry, UPDB, Utah Population Database
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Conflicts of interest Randall Burt is a consultant for Myriad Genetics, but has no conflict. The remaining authors disclose no conflicts.
Funding Research was supported by the Utah Cancer Registry, which is funded by contract N01-PC-35141 from the National Cancer Institute's Surveillance, Epidemiology, and End Results program with additional support from the Utah State Department of Health and the University of Utah. Partial support for all data sets within the Utah Population Database was provided by the University of Utah Huntsman Cancer Institute. Additional support was from R01, National Library of Medicine grant LM009331 (L.A.C.-A.), National Cancer Institute grants R01-CA40641 and PO1-CA73992 (R.W.B.), and an Intermountain Healthcare Homer Warner Center for Informatics Research Fellowship (D.P.T.).
PII: S0016-5085(09)02061-7
doi:10.1053/j.gastro.2009.11.044
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
