Expression of Xenobiotic Metabolizing Genes in Head and Neck Cancer Tissues


Background: Xenobiotic metabolizing genes are involved in detoxification of carcinogens. Expression ofthese enzymes may be one of the reasons for interindividual differences in head and neck cancer risks. The aimof current study was first to evaluate the expression of CYP1A1, GSTM1, GSTT1 and GSTP1 and second toobserve its relationship with stages of head and neck cancer in Pakistani population. Methodology: Fresh biopsytissues were taken from oncology institutional hospitals. Semi quantitative reverse transcriptase polymerasechain reaction was used to investigate CYP1A1, GSTM1, GSTT1 and GSTP1 expression in 49 head and neckcancer tumor tissue and 49 normal healthy tissues. Statistical analysis was performed to explore its associationwith head and neck cancer risk.
Results: The current study revealed that the CYP1A1 mRNA expression wasmarkedly reduced in tissues of head and neck carcinoma compared to adjacent normal tissue (OR 4.5, CI 1.5-13.4). CYP1A1 expression was downregulated in 62.5% tissues of stage 1, 72.7% tissues of stage 2, 60% tissuesof stage 3 and 100% tissues of stage 4. Undetectable or partial loss of expression of GSTM1 and GSTT1 mRNAwas also observed at a higher rate in head and neck cancer tissue compared to control (OR 4.5, CI 1.5- 13.4 andOR 3.2, CI 1.1- 9.6 respectively). GSTM1 and GSTT1 expression was also downregulated in stage wise pattern;stage 1 had 50% and 12.5% tissues showing down regulation of GSTM1 and GSTT1 genes respectively, bothGSTM1 and GSTT1 had 55% tissues with down regulation in stage 2, similarly stage 3 had 60% tissues showingdown regulation of these genes and stage 4 had 86% and 71% tumors. GSTP1 mRNA expression was significantlyhigher in cancer tissue as in control tissue (OR 4.2, CI 1.2- 15.3). GSTP1 over expression also revealed relatedto stages with 36.4%, 60% and 71% tumor of stage 2, 3 and 4 respectively.
Conclusion: Our results revealedthat CYP1A1, GSTM1 and GSTT1 are downregulated in the head and neck cancer progression while GSTP1 isupregulated. These down regulations and up regulation were more marked in advanced stages of head and neckcancer. Therefore, CYP and GST expression may be an important mechanism involved in the carcinogenesisbut the underlying mechanisms leading to such regulations in expression deserve further investigations.