Role of Genetic Variations of DNA Damage Response Pathway Genes and Heat-Shock Proteins in Increased Head and Neck Cancer Risk

Abstract

Aim:

The present study was designed to evaluate the role of DNA damage response pathway genes and heat-shock proteins in head and neck cancer (HNC) risk.

Methods:

For this purpose, two study cohorts were used. Cohort 1 (blood samples of 250 HNC patients and 250 controls) was used for polymorphism screening of selected genes using tetra-primer amplification refractory mutation system-polymerase chain (Tetra-ARMS PCR). Cohort 2 (200 HNC tumors and adjacent controls) was used for expression analysis, using quantitative PCR.

Results:

Analysis showed that mutant allele frequency of selected polymorphisms was found associated with increased HNC risk. Expression analysis showed the significant deregulation of selected genes in patients.

Conclusion:

The present study showed that selected genes (CHK1, CHK2, HSP70 and HSP90) can act as good diagnostic/prognostic markers in HNC.

Plain language summary

The present study is designed to identify the selected genes of DNA damage response pathway and heat-shock proteins as diagnostic/prognostic markers of head and neck cancer (HNC). To do this, DNA was isolated from blood samples and RNA isolated from the tissue samples of HNC patients. The mutation and expression level of selected genes was tested, and selected genes showed good diagnostic/prognostic values for HNC patients.

Keywords::

• CHK1
• CHK2
• DDR pathway
• HNC
• HSP70
• HSP90

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/fon-2022-0750

Author contributions

All of the authors read and approved the final version of manuscript. S Sheshe, T Shakoor and M Rizwan collected tissue samples, isolated the RNA samples and performed quantitative PCR experiments. A Mehmood, MS Haris, F Fazal and A Burki collected blood samples and performed SNPs analysis study. I Mahjabeen and MZ Hussain performed statistical analyses of the data and draft of the manuscript. MA Kayani and I Mahjabeen supervised the project and provided critical revisions. All the authors discussed the results and commented on the manuscript.

Acknowledgments

The authors acknowledge COMSATS University Islamabad and healthy controls/patients for their contribution in this project. The authors are also thankful to Holy Family and Pakistan Institute of Medical Sciences staff for their cooperation.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.