Abstract 2591: Risk prediction for stomach cancer using helicobacter pylori infection and atrophic gastritis, fruits and vegetables, smoking and GWAS-identified genetic polymorphism (PSCA-rs2294008) in a Japanese population

Abstract

Abstract [Background] Helicobacter pylori (H. pylori) infection and atrophic gastritis (AG) following H. pylori infection are well-established risk factors worldwide. Smoking is a convincing risk factor and fruits and vegetables intake is a possible protective factor in Japanese populations. PSCA-rs2294008 is one of single nucleotide polymorphisms (SNPs) with the susceptibility of a stomach cancer risk identified by Genome-wide association studies in Japanese populations. The advances in molecular evidence may have a potential to impact cancer prevention. However, it has never been clear how much it may contribute to cancer risk of the stomach on a population level in combination with environmental factors. In this study, we established a risk prediction model of stomach cancer using these environmental, clinical and genetic risk factors as a potential practical application in cancer preventive intervention. [Methods] We conducted two age- and sex- matched case-control studies, one for model derivation (697 cases and 1,372 controls) and the second (678 cases and 678 controls) for external validation. Based on data from the derivation study, a prediction model was developed by fitting a conditional logistic regression model using the following predictors: age, ABCD category defined by H.pylori infection and AG, smoking, fruits and vegetable intakes and PSCA genotype. Performance of the model was assessed in terms of discrimination (C statistic), calibration (calibration plots and Hosmer-Lemeshow test) and Integrated discrimination improvement (IDI) index. Cumulative risks were obtained by combining odds ratios estimated from the risk model with the age-specific incidence rate and population size. [Results] The risk model, including a combination of PSCA genotype, smoking, fruit & vegetable intake and alcohol consumption, provided high discriminatory accuracy and good calibration in both the derivation and validation studies: C statistics were 0.78 (95% confidence intervals 0.76-0.80) and 0.80 (0.77-0.82), respectively, and the calibration plots of both studies stayed close to the ideal calibration line. IDI indices are 0.11 and 0.12 (p<0.00001), respectively. [Conclusion] The risk prediction model that includes these environmental, clinical and genetic factors could be useful to classify Japanese into relevant risk groups of stomach cancer for personalized prevention programs. Citation Format: Hidemi Ito, Isao Oze, Satoyo Hosono, Miki Watanabe, Hideo Tanaka, Keitaro Matsuo. Risk prediction for stomach cancer using helicobacter pylori infection and atrophic gastritis, fruits and vegetables, smoking and GWAS-identified genetic polymorphism (PSCA-rs2294008) in a Japanese population. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2591.