Lung Adenocarcinoma and Squamous Cell Carcinoma in association with Genetic Polymorphisms of GSTs in Slovak Population

Abstract

Slovak Republic belongs to the countries with high incidence of lung cancer. Gene polymorphisms of the glutathione S-transferases (GSTs) may play a role in individual lung cancer susceptibility. In presented case-control study we investigate the incidence of polymorphism of GSTT1, GSTM1, GSTP1 genes and their combinations as possible predictive factors for identification of individuals with increased risk of formation and development of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of lung in Slovak population. The study was conducted on 520 individuals consisting of 118 patients with adenocarcinoma, 112 patients with squamous cell carcinoma and 290 control individuals. GSTT1, GSTM1, GSTP1 gene polymorphisms were assayed by standard PCR and PCR-RFLP technique. The results of this study indicate that the GSTT1null-genotype and combination GSTT1 null and Ile/Val or Val/Val are associated with increased risk of lung adenocarcinoma. A significant association with 2.13 -fold increased risk was observed between lung adenocarcinoma and GSTT1 null genotype (95% CI = 1.29 -3.51; p= 0.004). Also it was proved 2.83 times statistically higher risk for development of this histological type of lung cancer (95% CI = 1.34 -6.01; P = 0.005) in combination of GSTT1null and Ile/Val or Val/Val genotypes. GSTT1, GSTM1, GSTP1 polymorphism did not show any significant association with SCC. Our study suggests that genetic make-up in metabolizing genes may increase susceptibility towards lung cancer development.

Glutathione S-transferase pi 1 variant and squamous cell carcinoma susceptibility: a meta-analysis of 52 case-control studies

“…Similarly, inconsistent results regarding an association between the GSTP1 rs1695 A/G polymorphism and LSCC risk have been reported in different races and geographical locations [24, 31, 33, 34, 37, 40, 45, 47, 52, 56, 57, 60, 63]. Here, we failed to detect a positive correlation between GSTP1 rs1695 and LSCC susceptibility, consistent with the prior meta-analysis of Feng in 2013 [66] and Xu in 2014 [67].…”

Combined effects of glutathione S-transferase M1 and T1 polymorphisms on risk of lung cancer: evidence from a meta-analysis

“…It is possible that the effect sizes of genetic factors predisposing to human diseases are different in various ethnic populations [66]. Dzian et al [16], Matakova et al [18], and Cajas-Salazar et al [27] suggested that the combined effects of GSTM1 and GSTT1 polymorphisms increased lung cancer risk in Caucasians. Chen et al [22], Liang KC et al [56], Cao YF et al [45], Pan et al [39], Piao et al [40], and Zhang et al [38] suggested that the GSTM1 and GSTT1 polymorphisms in combination were associated with increased risk factors of lung cancer in Asians.…”