Comprehensive Analysis of the Association Between the rs1138272 Polymorphism of the GSTP1 Gene and Cancer Susceptibility

Abstract

Background: We obtained conflicting results regarding the relationship between the genetic role of the rs1138272 C/T polymorphism of the GSTP1 (Glutathione S-Transferase pi) gene and the risk of various cancers.Methods: Using the presently available data, a meta-analysis was conducted to comprehensively evaluate the genetic relationship between the GSTP1 rs1138272 polymorphism and cancer susceptibility.Results: A total of 43 studies including 15,688 cases and 17,143 controls were recruited into our quantitative synthesis. In the overall population, we observed an increased risk of overall cancer cases, compared with unrelated controls, in the genetic models of allele T vs. allele C (P-association = 0.007, OR = 1.17), carrier T vs. carrier C (P-association = 0.035, OR = 1.11), TT vs. CC (P-association = 0.002, OR = 1.45), TT vs. CC+CT (P-association = 0.009, OR = 1.42), and CT+TT vs. CC (P-association = 0.027, OR = 1.13). We detected similar positive results within the Asian population. Additionally, there was a significant increase in the incidence of cancer for Africans under all genetic models (all P-association < 0.05, OR > 1). When targeting the Caucasian population, we detected a positive association with the TT vs. CC and TT vs. CC+CT models in the “Colorectal cancer” (P-association < 0.05, OR < 1) and “Head and neck cancer” (P-association < 0.05, OR > 1) subgroups. For the “Lung cancer” subgroup, we observed a slightly increased risk in Caucasians under the models of allele T vs. allele C, carrier T vs. carrier C, CT vs. CC, and CT+TT vs. CC (P-association < 0.05, OR > 1).Conclusion: The TT genotype of the GSTP1 rs1138272 polymorphism is likely related to the susceptibility to overall cancer in the Asian and African populations and, specifically, “Colorectal” and “Head and neck” cancers in the Caucasian population. In addition, the CT genotype of the GSTP1 rs1138272 polymorphism may be linked to the risk of lung cancer in Caucasians. Additional evidence is required to confirm this conclusion.

Correlation of GSTP1 gene variants of male Iraqi waterpipe (Hookah) tobacco smokers and the risk of lung cancer

“…In addition, a meta-analysis conducted in 2013 in an Asian population, which included 28 case control studies, revealed that GSTP1-rs1138272 was associated with an increased risk of lung cancer [28]. Another meta-analysis included 43 studies with more than 15,000 cases and more than 17,000 controls, revealed that the GSTP1-rs1138272 (TT) genotype was more likely to be associated with cancers in Asian and African populations [29]. While the GSTP1-rs1138272 (CT) genotype was possibly related to lung cancer susceptibility in Caucasians [29].…”

“…Another meta-analysis included 43 studies with more than 15,000 cases and more than 17,000 controls, revealed that the GSTP1-rs1138272 (TT) genotype was more likely to be associated with cancers in Asian and African populations [29]. While the GSTP1-rs1138272 (CT) genotype was possibly related to lung cancer susceptibility in Caucasians [29]. No significant association between the GSTP1-rs1695: rs1138272 combinations (AA:CC), (GG:CC) and (GG:TT) and the risk of lung cancer was found in a Finnish population [30].…”

The Association of Polymorphisms in Nrf2 and Genes Involved in Redox Homeostasis in the Development and Progression of Clear Cell Renal Cell Carcinoma

“…However, since this SNP is located in the ARE-like motif of the gene, importance for self-induction of the Nrf2 is being emphasized throughout the literature [ 26 , 28 , 29 ]. In the case of GSTP1 gene polymorphisms, two most commonly occurring SNPs are rs1695 and rs1138272 [ 30 ]. Substitution of A313G in the case of rs1695 causes change of isoleucine with valine at position 105 (Ile105Val) [ 31 ].…”

The genetic role of Glutathione S-Transferase Mu 3 (GSTM3) intron 6 polymorphism in the susceptibility to cancer

“…There exist a group of genes, such as the Glutathione S-transferase alpha 1 (GSTA1), Glutathione S-transferase theta 1 (GSTT1), Glutathione S-Transferase pi (GSTP1), Glutathione S-transferase Mu1 (GSTM1) and Glutathione S-transferase Mu3 (GSTM3), in the GSTs supergene family [4,5]. In addition, several variants, such as present/null of GSTM1 or GSTT1 gene, rs1695, rs1138272 of GSTP1 gene, rs1799735 of GSTM3, were observed [6,7]. A deletion of three base pairs-induced GSTM3 rs1799735, also known as GSTM3 A/B or AGG/del, is situated in the intron 6 of the GSTM3 gene [8][9][10].…”

“…The variants with in the above GST family genes were reported to be associated with the genetic susceptibility to some clinical cancer diseases [6,7,11,12]. For example, GSTP1 rs1138272 polymorphism may be linked to the risk of overall cancer in the Asian and African populations.…”