Colorectal cancer risk based on extended family history and body mass index

Family history and body mass index (BMI) are well-known risk factors for colorectal cancer (CRC), however, their joint effects are not well described. Using linked data for genealogy, self-reported height and weight from driver's licenses, and the Utah Surveillance, Epidemiology, and End-Results cancer registry, we found that an increasing number of first-degree relatives (FDR) with CRC is associated with higher standardized incidence ratio (SIR) for overweight/obese probands but not for under/normal weight probands. For probands with two CRC-affected FDRs, the SIR = 1.91 (95% CI [0.52, 4.89]) for under/normal weight probands and SIR = 4.31 (95% CI [2.46, 7.00]) for overweight/obese probands. In the absence of CRC-affected FDRs, any number of CRC-affected SDRs did not significantly increase CRC risk for under/normal weight probands, but for overweight/obese probands with at least three CRC-affected SDRs the SIR = 2.68 (95% CI [1.29, 4.93]). In the absence of CRC-affected FDRs and SDRs, any number of CRC-affected third-degree relatives (TDRs) did not increase risk in under/normal weight probands, but significantly elevated risk for overweight/obese probands with at least two CRC-affected TDRs was observed; SIR = 1.32 (95% CI [1.04, 1.65]). For nonsyndromic CRC, maximum midlife BMI affects risk based on family history and should be taken into account for CRC risk communication when possible.