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Association between GSTP1, GSTM1 and GSTT1 polymorphisms involved in xenobiotic metabolism and head and neck cancer development

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Abstract

Polymorphisms in the glutathione S-transferase superfamily genes that encodes enzymes involved in the phase II xenobiotic metabolism may lead head and neck cancer development. In this study we investigate the association of A313G and C341T GSTP1 polymorphisms, GSTM1 and GSTT1 null genotypes in the head and neck cancer development, interactions between these polymorphisms,the tumor histopathologic parameters and risk factors (smoking and drinking) were also evaluated in the case–control study. 775 individuals (261 patients/514 controls) were included in the study. Molecular analyzes were performed by PCR and PCR–RFLP; and statistical analyzes by Chi square and multiple logistic regression. Chi square test showed that only the genotype frequencies for GSTM1 and GSTT1 were in Hardy–Weinberg disequilibrium in both groups. Significant results with p ≤ 0.05 showed that age ≥ 48 years (OR = 11.87; 7.55–18.65), smoking (OR = 4.25; 2.70–6.69), drinking (OR = 1.59; 1.02–2.46) were possible predictors for the head and neck cancer development and the presence of A313G GSTP1 polymorphism (OR = 0.62; 0.42–0.92) decreased the risk for this disease. Individuals with the 313AG/GG GSTP1 and age ≥ 48 years (OR = 0.59; 0.38–0.91), male gender (OR = 0.54; 0.35–0.83), smokers (OR = 0.63; 0.40–0.99) and drinkers (OR = 0.57; 0.35–0.95); the GSTM1 null genotype and age < 48 years (OR = 2.46; 1.09–5.55); the GSTT1 null genotype and primary anatomical sites of pharynx (OR = 0.37; 0.17–0.79) and larynx (OR = 3.60; 1.93–6.72), can modulate the risk for the disease development. The variables age ≥ 48 years, smoking and drinking can be predictors for head and neck cancer development; moreover, A313G GSTP1 polymorphism, GSTM1 and GSTT1 null genotypes can modulate the risk for this disease.

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Acknowledgments

The authors are grateful for the financial support of the “Fundação de Amparo à Pesquisa do Estado de São Paulo”-FAPESP, to “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior”-CAPES and “Conselho Nacional de Desenvolvimento Científico e Tecnológico”-CNPq and to support of FAMERP/FUNFARME. Jim Hesson of AcademicEnglishSolutions.com proofread the English.

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Russo, A., Francelin, P.R., Galbiatti, A.L.S. et al. Association between GSTP1, GSTM1 and GSTT1 polymorphisms involved in xenobiotic metabolism and head and neck cancer development. Mol Biol Rep 40, 4181–4188 (2013). https://doi.org/10.1007/s11033-013-2499-1

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  1. Eny Maria Goloni-Bertollo