Unusual Intronic Variant in GSTP1 in Head and Neck Cancer in Pakistan

Nosheen Masood,Faraz Arshad Malik,Mahmood Akhtar Kayani

doi:10.7314/apjcp.2012.13.4.1683

Nosheen Masood, Faraz Arshad Malik + Show 1 more

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https://doi.org/10.7314/apjcp.2012.13.4.1683

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Abstract

In the present case control study mRNA expression of the GSTP1 gene, encoding a phase II enzyme that detoxifies via glutathione conjugation, was investigated using semiquantitative PCR followed by SSCP for 49 confirmed head and neck (HN) cancer and 49 control samples. It was found that GSTP1 was upregulated in significantly higher number of cancers (OR 4.2, 95% CI 1.2- 15.3). Grade wise correlation was also observed with more up regulation in patients with more advanced grades of HN carcinomas. We also found that 5 patients showed variation in mRNA with a larger product size than expected. Sequencing revealed insertion of an intronic segment between the 6th and 7th exon of the GSTP1 gene. Germline screening was performed showing mobility shifts which suggested mutation at the DNA level resulting in intronic portion retention. This study is of prime importance for drug design and treatment selection to overcome increased resistance of HN cancers to drugs due to alteration in the GSTP1 gene.

Highlights

Head and neck cancers include cancers of oral cavity, larynx and pharynx
GSTP1 expression was upregulated in head and neck cancer patients. β actin was used as a housekeeping c)
As a complementary approach to confirm the above results, we sought whether the variants of GSTP1 were at sporadic level or germline level

Summary

Introduction

Head and neck cancers include cancers of oral cavity, larynx and pharynx. It is sixth most frequent cancer worldwide and is high in south East Asian countries (Johnson, 1991; Parkin et al, 2002) including Pakistan where it is second most prevalent cancer (Faheen, 2007).In humans, glutathione S transferases (GSTs), supergene family has four distinct isoforms (Mu, Theta, Pi and Alpha). Head and neck cancers include cancers of oral cavity, larynx and pharynx. It is sixth most frequent cancer worldwide and is high in south East Asian countries (Johnson, 1991; Parkin et al, 2002) including Pakistan where it is second most prevalent cancer (Faheen, 2007). Glutathione S transferases (GSTs), supergene family has four distinct isoforms (Mu, Theta, Pi and Alpha). Glutathione S transferase pi (GSTP1) is the predominant isoform in various malignant tumors of urinary, digestive and respiratory tracts (Nelson et al, 2001; Kim et al, 2009; Scharmach et al, 2009; Arun et al, 2010; Yu et al, 2010). GSTP1 is genetically polymorphic, and two GSTP1 nonsynonymous SNPs have been studied extensively in the epidemiological literature (Yang et al, 2006)

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