Inclusion of a gene-environment interaction between alcohol consumption and the aldehyde dehydrogenase 2 genotype in a risk prediction model for upper aerodigestive tract cancer in Japanese men.

Abstract

The well‐known gene‐environment interaction between alcohol consumption and aldehyde dehydrogenase 2 (ALDH2) genotype in upper aerodigestive tract cancer risk may improve our ability to identify high‐risk subjects. Here, we developed and validated risk prediction models for this cancer in Japanese men and evaluated whether adding the gene‐environment interaction to the model improved the predictive performance. We developed two case‐cohort datasets in the Japan Public Health Center‐based Prospective Study: one from subjects in the baseline survey for model development (108 cases and 4049 subcohort subjects) and the second from subjects in the 5‐year follow‐up survey for model validation (31 cases and 1527 subcohort subjects). We developed an environmental model including age, smoking status, and alcohol consumption, and a gene‐environment interaction model including age, smoking status, and the combination of alcohol consumption and the ALDH2 genotype. We found a statistically significant gene‐environment interaction for alcohol consumption and the ALDH2 genotype. The c‐index for the gene‐environment interaction model (0.71) was slightly higher than that for the environmental model (0.67). The values of integrated discrimination improvement and net reclassification improvement for the gene‐environment interaction model were also slightly higher than those for the environmental model. Goodness‐of‐fit tests suggested that the models were well calibrated. Results from external model validation by the 5‐year follow‐up survey were consistent with those from the model development by the baseline survey. The addition of a gene‐environment interaction to a lifestyle‐based model might improve the performance to estimate the probability of developing upper aerodigestive tract cancer for Japanese men.