Results
Our analysis included 687 men (cases, 133; controls, 554) and 476 women (cases, 54; controls, 422), 20-77 years of age. The number of prevalent cases of CRC identified was 166. An additional 22 incident cases of CRC occurred during follow-up. Table 1 details the general characteristics of case participants and control participants at baseline. The mean age (SD) was 42.9 (± 8.7) years for the study population-43.5 (± 8.9) for men and 42.0 (± 8.4) for women, respectively. No significant differences were observed in BMI, WC, systolic BP, or diastolic BP among case participants and control participants for both men and women (p > 0.05); however, case participants were older and had a family history of CRC more than control participants in both men and women (p < 0.001).
Table 2 indicates the area under the ROC curves for models that included both conventional risk factors and a genetic risk factor, GRS, compared with the AUC for the model that included only conventional risk factors. In the prediction model of CRC, we included age and family history of CRC as conventional risk factors and counted GRS or weighted GRS as genetic risk factors. For both men and women, including the GRS in the model increased the AUC over that observed when the AUC was based on only age or age and family history of CRC. For men, the AUC (95% CI) was 0.729 (range, 0.682 to 0.767) for conventional risk factors plus counted GRS (p < 0.001) and 0.719 (range, 0.677 to 0.761) for conventional risk factors plus weighted GRS (p < 0.001). The AUC (95% CI) was 0.692 (range, 0.647 to 0.732) for conventional risk factors alone. The increase in the AUC for the model with counted GRS was 0.042 and 0.032 for the model with weighted GRS. For women, the AUC (95% CI) was 0.650 (range, 0.615 to 0.680) for conventional risk factors plus counted GRS (p < 0.001) and 0.646 (range, 0.612 to 0.674) for conventional risk factors plus weighted GRS (p < 0.001). The AUC (95% CI) was 0.603 (range, 0.569 to 0.637) for conventional risk factors alone. The increase in the AUC for the model with counted GRS was 0.052 and 0.048 for the model with weighted GRS.
We further examined the association between GRS and CRC risk for both men and women in the KCPS-II, with stratification by family history of CRC (Fig. 1). The interaction between counted or weighted GRS and family history of CRC was significant in men, indicating a stronger genetic effect among participants with a positive family history of CRC than in those without it (p for interaction < 0.05) (ROC, 0.834 for counted GRS; ROC, 0.822 for weighted GRS). Women with a positive family history of CRC in the highest quartile of weighted GRS had an OR of 22.3 (95% CI, 1.4 to 344.2) and 18.1 (95% CI, 3.7 to 88.1) compared to those without a family history of CRC and counted or weighted GRS in the lowest quartile, respectively (ROC = 0.826 for counted GRS; ROC = 0.818 for weighted GRS). However, they were not statistically significant (p for interaction > 0.05). In addition, smoking, alcohol consumption, BMI, and WC did not interact significantly with GRS (data not shown).