Association between GSTM1 and GSTT1 Allelic Variants and Head and Neck Squamous Cell Cancinoma

Yang Zhang,Yuanyuan Ni,Yongchu Pan,Junqing Ma,Lin Wang,Hao Zhang,Andrzej T Slominski

doi:10.1371/journal.pone.0047579

Yang Zhang, Yuanyuan Ni + Show 5 more

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https://doi.org/10.1371/journal.pone.0047579

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Journal: PloS one	Publication Date: Oct 15, 2012
Citations: 15	License type: CC BY 4.0

Affiliation: Nanjing Medical University

Abstract

Backgrounds GSTM1 and GSTT1 are involved in the detoxification of carcinogens such as smoking by-products, and polymorphisms in these two genes with a result of loss of enzyme activity may increase risk of carcinogenesis. Although many epidemiological studies have investigated the association between GSTM1 or GSTT1 null genotype and head and neck squamous cell carcinoma (HNSCC), the results remain conflicting. To elucidate the overall association of GSTM1, GSTT1 and HNSCC, we included all available studies and performed this meta-analysis.Methodology/Principal FindingsA dataset including 42 articles for GSTM1, 32 articles for GSTT1, and 15 articles for GSTM1 and GSTT1 in combination were identified by a search in PubMed. Associations beween HNSCC and polymorphisms of GSTM1 and GSTT1 alone and in combination were analysed by software RevMan 5.1. Stratification analysis on ethnicity and smoking status, sensitivity analysis, heterogeneity among studies and their publication bias were also tested. Association was found in overall analysis between HNSCC and GSTM1 and GSTT1 null genotype. Stratified by ethnicity, we found increased risks of HNSCC in carriers with GSTM1 null genotype in Asian, GSTT1 null genotype in South American, and dual null genotype in European and Asian. When stratified by smoking, a more significant association of GSTM1 null genotype with HNSCC risk was observed in smokers.Conclusions/SignificanceThis meta-analysis presented additional evidence of the association between GSTM1 and GSTT1 polymorphisms and HNSCC risk.

Highlights

Head and neck neoplasms are the sixth leading cause of death by cancer [1]
glutathione S-transferase (GST) contribute to the detoxification of by-products of smoking and alcohol and other exogenous chemical carcinogens which may induce head and neck squamous cell carcinoma (HNSCC), so they have been considered as potential candidates for HNSCC susceptibility
42 studies described the association between GSTM1 null genotype and HNSCC, and 32 between GSTT1 null genotype and HNSCC

Summary

Introduction

Head and neck neoplasms are the sixth leading cause of death by cancer [1]. The most common histological type is the squamous cell carcinoma, accounting for about 90% of all cases [2,3]. The etiology of head and neck squamous cell carcinoma (HNSCC) is still a much debated question. Enzymes of the glutathione S-transferase (GST) family are present in eukaryotes and in prokaryotes, which are composed of many cytosolic, mitochondrial, and microsomal proteins. They catalyze various reactions and participate in the phase II biotransformation of xenobiotics. The GSTM1 and GSTT1 gene have been localized to chromosome 1p13.3 and 22q11.2. Both of the genes are polymorphic and frequent homozygous deletions of the genes presenting null genotype are associated with loss of the corresponding enzyme activity. Carriers with null genotype will increase the risk of the development of HNSCC due to the decreased ability to detoxify carcinogens theoretically

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