Abstract 1657: Genome-wide association study of lung cancer: Variation in TP63 gene confers the risk of lung adenocarcinoma

Abstract Lung cancer is the most common cause of death from cancer worldwide, and its incidence is increasing in East Asian and Western countries. Lung cancer comprises various types of histology that are often divided into two main types, non-small cell lung cancer and small cell lung cancer. Each type has different pathophysiological and clinical features, suggesting that their mechanisms of carcinogenesis differ. Adencarcinoma accounts for about 50% of all histological types of lung cancer, and its incidence is increasing in East Asian and Western countries. Because most of the current genome-wide association studies (GWAS) on lung cancer have been conducted in European populations with a full range of different histological types of lung cancer, GWAS that focus on individual histological groups with archived clinicopathological features are required. To identify genetic factors that modify the risk of lung adenocarcinoma, we conducted a genome-wide association study in a Japanese cohort, with replication in two independent studies in Japanese and Korean individuals, in a total of 2,098 lung adenocarcinoma cases and 11,048 controls. The combined analyses identified two susceptibility loci for lung adenocarcinoma: TERT (rs2736100, combined P = 2.91 × 10(-11), odds ratio (OR) = 1.27) and TP63 (rs10937405, combined P = 7.26 × 10(-12), OR = 1.31). When we analyzed the combinational combined effect of TP63 and TERT, we found that these two susceptibility genes showed a synergistic effect on the risk of lung adenocarcinoma (OR = 4.26). Fine mapping and re-sequencing of the region containing TP63 showed that a SNP (rs4488809) in intron 1 of TP63 showed the most significant association. Our results suggest that genetic variation in TP63 may influence susceptibility to lung adenocarcinoma in East Asian populations. Further functional studies are necessary to clarify the mechanisms by which TP63 influences susceptibility to lung adenocarcinoma. We will also report additional studies of TP63 on other ethnic populations as well as other histological types of lung cancer that will provide detailed information on the genetic etiology and heterogeneity of lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1657. doi:1538-7445.AM2012-1657