Abstract 4146: Polymorphisms of GSTT1, APE1 and MUTYh gene and the risk of oral squamous cell carcinoma

Abstract

Abstract In Taiwan, oral cancer (including sub-sites in the oral cavity, oropharynx and hypopharynx) is the fourth most common cancer in men. According to the cancer registry report from the Ministry of Health and Welfare of the Executive Yuan, the annual age-adjusted incidence for oral cancer in males has shown a 1.55-fold increase in the past decade. Cigarette smoking, areca quid (AQ) chewing and alcohol drinking have been unveiled as the major risk factors. Previous studies have implicated that oxidative stress generated from cigarette smoking, AQ chewing and alcohol drinking contributed to oral cancer development. It is well known that GSTM1 and GSTT1 are involved in the detoxification of oxidative free radicals and nearly all oxidative DNA lesions are repaired via the DNA base excision repair (BER) pathway. To investigate the role of GSTM1, GSTT1 and BER genes (including OGG1, APE1, MUTYh, WRN and XRCC1) involved in OSCC risk in Taiwan, a comprehensive study on evaluation of polymorphisms of above genes was carried out in 1139 OSCC male cases and 1470 general males. A significant effect of AQ chewing or AQ chewing combined with cigarette smoking or alcohol drinking on the risk of OSCC was observed. GSTT1 null genotype was significantly associated with an increased risk of OSCC (odds ratio (OR), 2.10; 95% confidence interval (CI), 1.64-2.68, p = 0.000000003). After adjustment for cigarette smoking, AQ chewing and alcohol drinking, GSTT1 null-type variant was still significantly associated with an increased risk of OSCC (OR= 2.00; 95% CI, 1.42-2.81, p = 0.00007), while GSTM1 was not associated with OSCC risk. Polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu, APE1 T-656G, MUTYh Gln324His, WRN Cys1367Arg, and XRCC1 Arg399Gln were not associated with OSCC risk in general. However, stratification analysis indicated that polymorphisms of APE1 Asp148Glu and MUTYh Gln324His were associated with OSCC risk in individuals with cigarette smoking combined with AQ chewing. Furthermore, those individuals with either APE1 148 Asp/Asp or MUTYh 324 His/His genotype had an increased OSCC risks when compared to those with APE1 148 Glu and MUTYh 324 Gln allele (OR = 1.48; 95% CI, 1.13-1.95, p = 0.005). In conclusion, our results demonstrated that polymorphisms of genes involved in detoxification and BER of oxidative stress could influence the OSCC risk especially for those have history of cigarette smoking and AQ chewing. Citation Format: Chih-Hsiung Lai, Li-Ling Chiu, Huei-Tzu Chien, Saou-Hsing Liou, Shiang-Fu Huang, I-How Chen, Chun-Ta Liao, Ling-Ling Hsieh. Polymorphisms of GSTT1, APE1 and MUTYh gene and the risk of oral squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4146. doi:10.1158/1538-7445.AM2014-4146