Genetic polymorphism of lysyl oxidase, glutathione S-transferase M1, glutathione-S-transferase T1, and glutathione S-transferase P1 genes as risk factors for lung cancer in Egyptian patients
- 30 May 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Biology Reports
- Vol. 48 (5), 4221-4232
- https://doi.org/10.1007/s11033-021-06436-4
Abstract
Lung cancer is a lethal malignancy and is affected by genetic polymorphisms that contribute to an individual’s susceptibility to developing the disease. Several studies on lung cancer showed conflicting results. The aim of this study is to investigate whether individual or combined modifying effects of LOX G/A, GSTM1 active/null, GSTT1 active/null and GSTP1 Ile/Val polymorphisms are related to the risk of lung cancer in relation to smoking in the Egyptian population. This study is a hospital-based case control study that included 200 patients and 200 control subjects. Genotyping of the 4 studied genes was determined by Multiplex PCR for GSTM1 and GSTT1 and Taq man SNP assay for GSTP1 and LOX genes. The LOX G/A and GSTP1 Ile/Val in both homozygous and heterozygous variants, and the GSTM1 and GSTT1 null genotype showed significant association with lung cancer. Combination between gene polymorphism and smoking increased the risk of developing cancer by 2.7 fold in the LOX GA+AA variant, 1.9 fold in the GSTM1 null variant, 4.8 fold in the GSTT1 null variant and 4.3 fold in the GSTP1 Ile/Val+Val/Val variant. The genetic combination (LOX GA+AA/GSTT1 active, LOX GG/GSTT1 null, LOX GA+AA/GSTT1 null, LOX GA+AA/GSTP1 Ile/Ile, LOX GG/GSTP1 Ile/Val+Val/Val and LOX GA+AA/GSTP1 Ile/Val+Val/Val) led to a higher lung cancer risk, compared to the reference group. The LOX GA/AA, GSTM1 null, GSTT1 null and GSTP1 Ile/Val, Val/Val genotypes contributed to increased lung cancer susceptibility. To the best of our knowledge, this is the first study of LOX genotyping in the Egyptian population. The combination of genotypes increased the risk of cancer, indicating the importance of gene–gene interaction and giving a targeted preventive approach.Keywords
Funding Information
- Scientific Research Foundation for Returned Scholars of Ministry of Education (5424)
This publication has 54 references indexed in Scilit:
- Polymorphisms at GSTM 1, GSTP 1, GSTT 1 Detoxification Genes Loci and Risk of Breast Cancer in Kazakhstan PopulationAdvances in Breast Cancer Research, 2013
- Genetic polymorphisms in CYP1A1, GSTM1, GSTP1 and GSTT1metabolic genes and risk of lung cancer in AsturiasBMC Cancer, 2012
- Lysyl Oxidase Polymorphisms and Susceptibility to OsteosarcomaPLOS ONE, 2012
- Correlation of CYP1A1, GSTP1 and GSTM1 gene polymorphisms and lung cancer risk among smokersOncology Letters, 2012
- Variants in Exon 11 of MEF2A Gene and Coronary Artery Disease: Evidence from a Case-Control Study, Systematic Review, and Meta-AnalysisPLOS ONE, 2012
- Functional genetic polymorphisms and female reproductive disorders: Part II--endometriosisHuman Reproduction Update, 2008
- Influence of p53 codon 72 exon 4, GSTM1, GSTT1 and GSTP1*B polymorphisms in lung cancer risk in a Brazilian populationLung Cancer, 2008
- Association of GST Genes Polymorphisms with Asthma in Tunisian ChildrenMediators of Inflammation, 2007
- Five Glutathione S-Transferase Gene Variants in 23,452 Cases of Lung Cancer and 30,397 Controls: Meta-Analysis of 130 StudiesPLoS Medicine, 2006
- GSTM1, GSTT1 and GSTP1 polymorphisms, environmental tobacco smoke exposure and risk of lung cancer among never smokers: a population-based studyCarcinogenesis: Integrative Cancer Research, 2004