Association between genetic polymorphisms of hOGG1 and APE1 and the risk of Taiwanese lung cancer: the contribution in p53 and EGFR deletion mutations

• Main Authors: Po-Ming, 陳柏銘
• Other Authors: 李輝
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/39995079109630826364

碩士 === 中山醫學大學 === 醫學分子毒理學研究所 === 94 === Neoplasm is the leading cause of death in Taiwanese people since 1982. Among the cancers, lung cancer is the leading cause of cancer death in women and the second cause of cancer death in men. Cigarette smoking is the major cause of lung cancer, however, the cigarette consumption is gradually decreased, the lung cancer motarity rate is remarkablly increased, espcially in lung adenocarcinomas. The pathogenesis of lung adenocarcinoma is unclear, but chronic inflammation is considered to associate with developing lung adenocarcinoma. Reactive oxgen species (ROS) is linked with chronic inflammation and cancer development. Therefore, the association between genetic polymorphisms of base excision repair genes and human cancers have been extensively investigated including lung cancer, especially in hOGG1 ser326Cys and APE1 Asp148Glu. However, the conflicting results were reported in several studies. The genetic polymorphisms of both genes were not studied in Taiwanese population, except the study on the assocation between hOGG1 and NPC. Thus, In this study, 205 lung cancer cases and 206 mached non-cancer hospital controls were enrolled to verify the association between both genetic polymorphisms and lung cancer risk. The genetic polymorphisms were determined by PCR-RFLP and PCR-CTPP, respectively. Our data indicated that subject with hOGG1 Ser/Cys, Cys/Cys variants had 2.01 fold of lung cancer risk as compared with that of Ser/Ser genotype. Being stratified three categories by gender and cigarette smoking, the the lung cancer risk of variant genotypes was increased to 2.61- and 2.72-fold in smoking male and nonsmoking female subjects, respectively, but not observed in nonsmoking male subjects. Interestingly, the lung cancer risk of subject with APE1 Asp/Glu + Glu/Glu variants was 0.53-fold of that of Asp/Asp genotype. Among these categories, only smoking male subject with APE1 variants had about one-half of lung cancer risk (OR = 0.49). When combined the genotypes of both genes, the lung cancer risk was increased in subject with variants of hOGG1 and APE1 (OR = 2.80), Asp/Asp and Ser/Ser (OR = 3.20), and Asp/Asp and Ser/Cys + Cys/Cys (OR = 4.15) as compared with subject with the combination of APE1 variants and hOGG1 Ser/Ser genotype (OR = 1). These results suggest that gene-gene interaction of hOGG1 and APE1 may increase the lung cancer risk in Taiwanese population. On the other hands, we futher understand the correlation between both genetic polymorphisms and p53 and EGFR mutations in lung cancer patients. Our data indicated that patients with APE1 Asp/Asp genotype had 1.77-fold risk of p53 mutation occurrence as compared with those of variants, moreover, the risk of p53 mutation was increased to 2.84-fold in patients with the combined genotypes of Asp/Asp and Ser/Ser. More interestingly, the deletion mutation of p53 and EGFR was frequently occurred in patients with hOGG1 variant genotypes. These results suggest that hOGG1 and APE1 involved in the removal oxidative DNA damage plays an important role in lung carcinogenesis, at least in Taiwanese population.