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

• Published in: Cancer science Vol. 111; no. 10; pp. 3835 - 3844
• Main Authors: Iwasaki, Motoki, Budhathoki, Sanjeev, Yamaji, Taiki, Tanaka‐Mizuno, Sachiko, Kuchiba, Aya, Sawada, Norie, Goto, Atsushi, Shimazu, Taichi, Inoue, Manami, Tsugane, Shoichiro
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.10.2020; John Wiley and Sons Inc
• Subjects: absolute risk; Accuracy; Adult; Aged; Alcohol; Alcohol Drinking - genetics; Alcohol Drinking - pathology; Alcohol use; Aldehyde dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial - genetics; Aldehydes; Cancer; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Dehydrogenases; Epidemiology and Prevention; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Ethanol; Gene-Environment Interaction; Genetic Predisposition to Disease; Genotype & phenotype; Genotype-environment interactions; Genotypes; Health facilities; Humans; Male; Middle Aged; Oncology; Original; Prediction models; Public health; Questionnaires; Reclassification; Response rates; Risk Factors; risk prediction model; single‐nucleotide polymorphisms; Smoking; Statistical analysis; Surveys; upper aerodigestive tract cancer; Womens health; Japan; absolute risk; risk prediction model; single-nucleotide polymorphisms; upper aerodigestive tract cancer; gene-environment interaction
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.14573

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. We developed and validated risk prediction models for upper aerodigestive tract cancer in Japanese men based on a prospective cohort study. We demonstrated that the addition of the gene‐environment interaction between alcohol consumption and aldehyde dehydrogenase 2 genotype on upper aerodigestive tract cancer risk to a lifestyle‐based model improved the performance to estimate the probability of developing this risk.