Relationship of Single Nucleotide Polymorphisms and Haplotype Interaction of Mitochondrial Unfolded Protein Response Pathway Genes with Head and Neck Cancer

Abstract

Aim: In this study, we evaluated the effect of selected polymorphisms of mitochondrial unfolded protein response (UPR^mt) pathway in 500 head and neck cancer (HNC) patients and 500 healthy controls from Pakistan. Materials&methods: The experiments were conducted using tetra-ARMS PCR followed by DNA sequencing. Results: Multivariate analysis showed that AA genotype of rs3782116 showed fivefold, GG genotype of rs6598072 approximately twofold and CC genotype of rs4946936 and TT genotype of rs12212067 showed twofold increased risk of HNC. Furthermore, haplotype analysis showed that certain haplotypes of UPR^mt pathway single nucleotide polymorphisms have significant association with increased HNC risk. Conclusion: These results show that genetic aberrations in UPR^mt pathway genes have association with increased HNC risk and can be an indicator of advance clinical outcome especially invasion and metastasis.

Keywords::

• clinical outcome
• haplotype analysis
• HNC
• metastasis
• UPR^mt mechanism

Author contributions

All of the authors read and approved the final version of manuscript. MW Ahmed, S Gul and A Khursheed collected and isolated the DNA samples. MW Ahmed and A Mehmood performed the genotyping and drafted the manuscript. I Mahjabeen performed the genotyping studies, statistical analyses of the data and draft of the manuscript. MA Kayani supervised the project, helped to analyze the statistical data and provided critical revisions. All of the authors discussed the results and commented on the manuscript.

Acknowledgments

Authors are thankful to patients and staff of Nuclear Medicine Oncology and Radiotherapy Institute, Islamabad, for contribution in this research.

Financial&competing interests disclosure

The authors received financial and infrastructural support from Higher Education Commission of Pakistan and COMSATS University, Islamabad. The authors have no other 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 apart from those disclosed.

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

Additional information

Funding

The authors received financial and infrastructural support from Higher Education Commission of Pakistan and COMSATS University, Islamabad. The authors have no other 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 apart from those disclosed. No writing assistance was utilized in the production of this manuscript.