title: Development of a prediction model and estimation of cumulative risk for upper aerodigestive tract cancer on the basis of the aldehyde dehydrogenase 2 genotype and alcohol consumption in a Japanese population.
abstract: Alcohol consumption and the aldehyde dehydrogenase 2 (ALDH2) polymorphism are associated with the risk of upper aerodigestive tract cancer, and a significant gene-environment interaction between the two has been confirmed in a Japanese population. To aid the development of a personalized prevention strategy, we developed a risk-prediction model and estimated absolute risks stratified by a combination of the ALDH2 genotype and alcohol consumption. We carried out two age-matched and sex-matched case-control studies: one (630 cases and 1260 controls) for model derivation and the second (654 cases and 654 controls) for external validation. On the basis of data from the derivation study, a prediction model was developed by fitting a conditional logistic regression model using the following predictors: age, sex, smoking, drinking, and the ALDH2 genotype. The risk model, including a combination of the ALDH2 genotype and alcohol consumption, provided high discriminatory accuracy and good calibration in both the derivation and the validation studies: C statistics were 0.82 (95% confidence interval 0.80-0.84) and 0.83 (95% confidence interval 0.81-0.85), respectively, and the calibration plots of both studies remained close to the ideal calibration line. Cumulative risks were obtained by combining odds ratios estimated from the risk model with the age-specific incidence rate and population size. For heavy drinkers with a heterozygous genotype, the cumulative risk at age 80 was above 20%. In contrast, risk in the other groups was less than 5%. In conclusion, modification of alcohol consumption according to the ALDH2 genotype will have a major impact on upper aerodigestive tract cancer prevention. These findings represent a simple and practical model for personalized cancer prevention.
authors: aDepartment of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka bDivision of Epidemiology and Prevention cDivision of Molecular Medicine, Aichi Cancer Center Research Institute Departments of dGastrointestinal Surgery eHead and Neck Surgery, Aichi Cancer Center Hospital fDepartment of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yuriko N
authors: YN
authors: Koyanagi
authors: Hidemi
authors: H
authors: Ito
authors: Isao
authors: I
authors: Oze
authors: Satoyo
authors: S
authors: Hosono
authors: Hideo
authors: H
authors: Tanaka
authors: Tetsuya
authors: T
authors: Abe
authors: Yasuhiro
authors: Y
authors: Shimizu
authors: Yasuhisa
authors: Y
authors: Hasegawa
authors: Keitaro
authors: K
authors: Matsuo
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology* / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011159:Population Surveillance / Q000379:methods; D011237:Predictive Value of Tests; D012307:Risk Factors
chemical_list: C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial