Investigation of Genetic Polymorphisms Related GSTM1, GSTT1, GSTP1 Genes and their Association with Radiotherapy Toxicity among Head and Neck Cancer Patients.

Abstract

Background: In this study we explored the association of polymorphisms of glutathione s transferase gene including GSTM1, GSTT1 and GSTP1 with adverse acute normal tissue reactions resulted from radiotherapy in HNC patients. We assessed the association of GSTM1 and GSTT1 null genotypes and Ile105Val of exon-5 and Ala114Val of exon-6 of GSTP1 gene polymorphisms with the risk of acute skin toxicity reactions after therapeutic radiotherapy in HNC patients.

Methods: Four hundred HNC patients administered with Intensity modulated radiation therapy were enrolled in this study for the evaluation of radiotherapy associated toxicity reactions. The genotyping of GSTM1 and GSTT1 were performed by polymerase chain reaction (PCR). The GSTP1 Ile/Val of exon-5 and Ala/Val of exon-6 polymorphism was determined by PCR followed by restriction fragment length polymorphism (PCR-RFLP).

Results: The univariate logistic regression analysis showed that GSTM1 and GSTT1 null genotypes were not associated with either skin reaction or oral mucositis in response to radiotherapy induced after effects. When we studied, A313G polymorphism at exon 5 and C341T polymorphism at exon 6 of GSTP1 gene, majority of genotypes were wild type A/A genotype for exon 5 showed non-significant association with Skin reactions whereas, C/T genotype of exon-6 showed significant negative association with skin reactions.

Conclusion: The findings obtained from this study concluded that the null genotypes of GSTM1 and GSTT1 gene polymorphisms showed no association with radiotherapy induced acute toxicities such as dermatitis and oral mucositis. The results indicated negative association of heterozygous C/T genotype of exon-6 of GSTP1 with acute skin reactions.