Unusual intronic variant in GSTP1 in head and neck cancer in Pakistan.
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.
Department of Biosciences, COMSATS Institute of Information and Technology, Islamabad, Pakistan. nosheenmasood@hotmail.com
Nosheen
N
Masood
Faraz Arshad
FA
Malik
Mahmood Akhtar
MA
Kayani
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016017:Odds Ratio; D010154:Pakistan; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015854:Up-Regulation / Q000235:genetics
D012333:RNA, Messenger; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi