Abstract 1860: Association of esophageal cancer risk with genetic polymorphisms of xenobiotic metabolizing genes, DNA repair genes, and inflammation-regulating genes in Huaian, China

Abstract

Abstract Accumulating evidences suggest that both exposure to environmental carcinogens and individual susceptibility factors contribute to the formation of esophageal cancer. Huaian City is one of the highest risk areas of esophageal cancer in China with the annual incidence over 100/100,000 people. To explore etiological risk factors contributing to the high rate of esophageal cancer, a population-based case-control study was conducted in 185 esophageal squamous cell carcinoma (ESCC) cases and 515 age-, gender-, and residency-matched healthy controls in Huaian. Our previous study found an association between dietary fumonisin exposure and ESCC risk in this population. In the present study, we further investigated the association between ESCC and polymorphic genes involving in xenobiotic metabolizing activities, DNA repair, and inflammation regulation including GSTM1, GSTT1, XPD (Lys751Gln), hOGG1 (Ser326Cys), TNF-α (G308A), NF-κB (−94ins/delATTG), COX-2 (G765C), and iNOS (Ser608Leu). Genetic polymorphisms of GSTM1 and GSTT1 were determined by multiplex PCR and other polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP) analysis using genomic DNA samples obtained from lymphocytes of study subjects. The prevalence of GSTT1 null genotype was significantly higher in cases (53.51%) than in controls (41.94%) (p=0.0067), with an age- and gender-adjusted odds ratio (OR) of 1.68 and 95% confidence interval (CI) of 1.18 − 2.39. After stratifying by gender, GSTT1 null type was found more prevalent in male cases (57.14%) than in male controls (42.64%) (p=0.0117). XPD Lys751Gln polymorphism was associated with increased ESCC risk (age- and gender-adjusted OR=1.74, 95% CI: 1.11-2.74). XPD heterozygous and mutant genotypes (Lys/Gln+Gln/Gln) were more prevalent in cases (20.54%) than in controls (14.26%) (p=0.0453), and in female cases (24.32%) than in female controls (13.01%) (p=0.0187). Heterozygous genotype of TNF-α was found in 12.97% of cases and 7.65% of controls, showing a marginal increased risk of ESCC (adjusted OR=1.68, 95% CI: 0.95-2.98). These results suggest that polymorphisms of GSTT1, XPD and TNF-α gene may contribute to ESCC risk in this high-risk population. (Supported by NIH/NCI grants, CA94683 and CA90997). Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1860.