Lack of Associations between Genetic Polymorphisms in GSTM1, GSTT1 and GSTP1 and Pancreatic Cancer Risk: A Multi-Institutional Case-Control Study in Japan

Abstract

<b>Background:</b> We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizinggenes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. Materialsand <br/><b>Methods</b>: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1,GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilicmolecules. The study population consisted of 360 patients and 400 control subjects, who were recruited fromseveral medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios(ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk.<br/><b>Results</b>: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotypewas approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 andGSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated withthe risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-nullgenotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) forindividuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1-present genotypes. No synergistic effects of smoking or GST genotypes were observed. <br/><b>Conclusions</b>: Our resultsindicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancerrisk in the Japanese subjects in our study.