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Expression of xenobiotic metabolizing genes in head and neck cancer tissues
Nosheen Masood1, Fraz Arshad Malik, Mahmood Akhtar Kayani
1COMSATS Institute of Information and Technology, Islamabad, Pakistan.
Background:
Xenobiotic metabolizing genes are involved in detoxification of carcinogens. Expression of these enzymes may be one of the reasons for interindividual differences in head and neck cancer risks. The aim of current study was first to evaluate the expression of CYP1A1, GSTM1, GSTT1 and GSTP1 and second to observe its relationship with stages of head and neck cancer in Pakistani population.
Methodology:
Fresh biopsy tissues were taken from oncology institutional hospitals. Semi quantitative reverse transcriptase polymerase chain reaction was used to investigate CYP1A1, GSTM1, GSTT1 and GSTP1 expression in 49 head and neck cancer tumor tissue and 49 normal healthy tissues. Statistical analysis was performed to explore its association with head and neck cancer risk.
Results:
The current study revealed that the CYP1A1 mRNA expression was markedly 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% tissues of stage 3 and 100% tissues of stage 4. Undetectable or partial loss of expression of GSTM1 and GSTT1 mRNA was also observed at a higher rate in head and neck cancer tissue compared to control (OR 4.5, CI 1.5- 13.4 and OR 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, both GSTM1 and GSTT1 had 55% tissues with down regulation in stage 2, similarly stage 3 had 60% tissues showing down regulation of these genes and stage 4 had 86% and 71% tumors. GSTP1 mRNA expression was significantly higher in cancer tissue as in control tissue (OR 4.2, CI 1.2- 15.3). GSTP1 over expression also revealed related to stages with 36.4%, 60% and 71% tumor of stage 2, 3 and 4 respectively.
Conclusion:
Our results revealed that CYP1A1, GSTM1 and GSTT1 are downregulated in the head and neck cancer progression while GSTP1 is upregulated. These down regulations and up regulation were more marked in advanced stages of head and neck cancer. Therefore, CYP and GST expression may be an important mechanism involved in the carcinogenesis but the underlying mechanisms leading to such regulations in expression deserve further investigations.
Insights
Expression of detoxification genes CYP1A1, GSTM1, and GSTT1 decreases in head and neck cancer, while GSTP1 increases. These changes are more pronounced in advanced cancer stages, suggesting a role in carcinogenesis.
Area of Science:
- Genetics
- Oncology
- Biochemistry
Background:
- Xenobiotic metabolizing genes are crucial for carcinogen detoxification.
- Variations in these enzyme expressions contribute to individual differences in cancer risk.
- Head and neck cancer (HNC) risk may be influenced by these genetic factors.
Purpose of the Study:
- To evaluate the expression of CYP1A1, GSTM1, GSTT1, and GSTP1 genes in HNC.
- To investigate the correlation between the expression of these genes and the clinical stages of HNC in a Pakistani population.
Main Methods:
- Biopsy tissues from 49 HNC patients and 49 healthy individuals were analyzed.
- Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was employed to measure gene expression.
- Statistical analyses were performed to determine associations with HNC risk and stage.
Main Results:
- CYP1A1 mRNA expression was significantly reduced in HNC tissues compared to normal tissues, with downregulation more severe in advanced stages.
- GSTM1 and GSTT1 mRNA expression showed decreased levels or loss of expression in HNC tissues, also stage-dependently.
- GSTP1 mRNA expression was significantly higher in HNC tissues, with overexpression correlating with advanced cancer stages.
Conclusions:
- CYP1A1, GSTM1, and GSTT1 are downregulated in HNC progression, while GSTP1 is upregulated.
- These expression changes are more pronounced in advanced HNC stages.
- Altered CYP and GST gene expression represents a potential mechanism in HNC carcinogenesis, warranting further mechanistic investigation.
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