No role for glutathione S-transferase genotypes in Caucasian esophageal squamous cell or adenocarcinoma etiology: an European case–control study

Abstract

BackgroundIdentifying and monitoring high-risk patients can aid the prevention of esophageal cancer (EC). The interaction of environmental risk factor exposure and genetic susceptibility may contribute to the etiology of EC. Biotransformation enzymes such as Glutathione S-Transferases (GSTs ) detoxify mutagenic and genotoxic compounds and therefore control the rate of detoxification of carcinogens. Functional polymorphisms in the genes coding for GSTs alter their enzyme activity in vitro, and were reported to modify EC risk in Asians. We hypothesized that altered enzyme activity GST genotypes influence the susceptibility for esophageal adeno- (EAC) and squamous cell carcinoma (ESCC) in Caucasians.MethodsWe performed a case–control study including 440 Caucasian patients with EC and 592 healthy Caucasian controls matched for age and sex. Functional polymorphisms were selected and genotypes were determined in GST classes Alpha, Mu, Theta and Pi by means of polymerase chain reaction. Genotypes were classified into predicted high, intermediate and low enzyme activity categories based on in vitro activity data. The distribution of the activity genotypes were compared between patients with EAC or ESCC, and controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by logistic regression analyses. Gene-gene interactions were tested and for comparison purposes, the predicted low and intermediate activity genotypes were combined. Genotypes with similar risks for EAC or ESCC were combined and analyzed for multiplicative effects.ResultsOur analyses includes 327 patients with EAC and 106 patients with ESCC. Low or intermediate activity enzyme genotypes for GSTM1, GSTA1, GSTP1 I105V and A114V as well as for GSTT1, did not significantly modify the risk for ESCC or EAC in our Dutch population.ConclusionFunctional genotypes in GST genes are not involved in EAC or ESCC susceptibility in Caucasians, in contrast to results on ESCC from Asia or Africa.

GST Theta null genotype is associated with an increased risk for ulcerative colitis: a case–control study and meta-analysis of GST Mu and GST Theta polymorphisms in inflammatory bowel disease

“…Polymorphisms in GSTM1 and GSTT1 were analyzed using PCR as described previously. 15 The primers 5 0 -CTGGATTGTA GCAGATCATGC-3 0 /5 0 -CTCCTGATTATGACAGAAGCC-3 0 and 5 0 -TCACCGG ATCATGGCCAGCA-3 0 /5 0 -TTCCTTACTGGTCCTCACATCTC-3 0 were used for GSTM1 and GSTT1, respectively. To detect GSTM1 and GSTT1 genotypes, melt curve analysis was applied using the Bio-Rad Precision Melt Analysis Software version 1.0 (Bio-Rad, Hercules, CA, USA) and in this way homozygous and heterozygous most common genotypes could be distinguished from homozygous GSTM1*0 (null) or GSTT1*0 (null) genotypes.…”

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

“…An additional 56 articles were excluded, including 56 articles with unavailable data on the genotype frequency of CC, CT, and TT within GSTP1 rs1138272, and 4 articles in which the data were not in HWE. After a quality evaluation, 40 articles (Harris et al, 1998; Saarikoski et al, 1998; Park et al, 1999; Wadelius et al, 1999; Welfare et al, 1999; Marshall et al, 2000; Stanulla et al, 2000; Krajinovic et al, 2002; Wang et al, 2003, 2011; Sorensen et al, 2004; Yang et al, 2004; Garcia-Closas et al, 2005; Landi et al, 2005, 2007; Moore et al, 2005; De Roos et al, 2006; Lira et al, 2006; Marciniak et al, 2006; Jiao et al, 2007; Li et al, 2007, 2010; Murphy et al, 2007; Al-Dayel et al, 2008; Kury et al, 2008; Siraj et al, 2008; Van Emburgh et al, 2008; Zienolddiny et al, 2008; Canova et al, 2009; Northwood et al, 2010; Sainz et al, 2011; Ebrahimkhani et al, 2012; Garcia-Gonzalez et al, 2012; Ibarrola-Villava et al, 2012; Dura et al, 2013; Oskina et al, 2014; Ghatak et al, 2016; De Mattia et al, 2017; Minina et al, 2017; Rajesh et al, 2018) of good quality were included. Finally, we included a total of 43 case-control studies for our quantitative synthesis.…”

“…We removed one case-control study in which the data were not in HWE (Marie-Genica Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer Risk, 2010), and we removed two additional studies (Barnette et al, 2004) because they failed to meet the requirement of reporting the genotype frequency in both the case and control group. Moreover, 17 new articles (Park et al, 1999; Welfare et al, 1999; Marshall et al, 2000; Stanulla et al, 2000; Krajinovic et al, 2002; De Roos et al, 2006; Lira et al, 2006; Li et al, 2007, 2010; Sainz et al, 2011; Garcia-Gonzalez et al, 2012; Dura et al, 2013; Oskina et al, 2014; Ghatak et al, 2016; De Mattia et al, 2017; Minina et al, 2017; Rajesh et al, 2018) were added. Finally, a total of 40 articles were included in our updated meta-analysis.…”

Association between GSTM1 and GSTT1 polymorphisms and esophageal squamous cell carcinoma: results from a case-control study in Kashmir, India

“…A meta-analysis also reported a significant association between GSTT1 polymorphism and ESCC risk in Asian populations (OR = 1.26, 95 %CI = 1.05-1.52) [36]. However, this association has not been supported by studies from low-incidence areas, including Japan and Europe [37]. The reason for this heterogeneity is unclear and needs further investigation, but one may speculate that people in high-incidence areas are exposed to much higher levels of certain xenobiotic compounds that need detoxification by the GSTT1 gene.…”