title: Associations of GSTM1 and GSTT1 polymorphisms with pancreatic cancer risk: evidence from a meta-analysis.
abstract: Glutathione S-transferases (GSTs), including glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1), are multifunctional enzymes which play vital roles in the detoxification of a variety of carcinogens. The genetic polymorphisms of GSTM1 and GSTT1 have been implicated in pancreatic cancer risk, but the results of published studies remain conflicting. Thus, a meta-analysis was conducted to estimate the effect of GSTM1 and GSTT1 polymorphisms on the risk of developing pancreatic cancer. A comprehensive search was performed in the PubMed, Embase, Web of Science, and Wanfang databases to identify the available studies on the associations of GSTM1 and GSTT1 polymorphisms with pancreatic cancer risk. The pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) was used to estimate the associations. Stratified analyses by ethnicity and sensitivity analyses were performed to further identify the relationships. Overall, the null genotype of GSTT1 was associated with an increased risk of pancreatic cancer (OR = 1.61, 95 % CI 1.06-2.44, P OR = 0.025), but similar association was not found between the null genotype of GSTM1 and pancreatic cancer risk. Besides, a significant association of GSTT1 polymorphism with pancreatic cancer risk was identified in Asians (OR = 2.58, 95 % CI 1.67-3.98, P OR < 0.001), but not in Caucasians (OR = 1.16, 95 % CI 0.94-1.43, P OR = 0.170). Sensitivity analyses by sequential omission of individual study confirmed the stability of our results. Meta-analysis of available data thus far shows that the null genotype of GSTT1 is a risk factor for pancreatic cancer, particularly in the Asian population. The currently available data are not sufficient enough to identify the association between the GSTM1 polymorphism and pancreatic cancer risk.
authors.affiliation: Department of Integrated TCM & Western Medicine, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road Fenglin Street, Shanghai, 200032, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Fan
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Chen-Ye
authors.initials: CY
authors.lastname: Shi
authors.forename: Ding-Fang
authors.initials: DF
authors.lastname: Cai
mesh_terms: D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000209:etiology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D005982:Glutathione Transferase; C413545:glutathione S-transferase T1