In this study, we evaluated the effect of selected polymorphisms of mitochondrial unfolded protein response (UPR) pathway in 500 head and neck cancer (HNC) patients and 500 healthy controls from Pakistan. The experiments were conducted using tetra-ARMS PCR followed by DNA sequencing. 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 pathway single nucleotide polymorphisms have significant association with increased HNC risk. These results show that genetic aberrations in UPR pathway genes have association with increased HNC risk and can be an indicator of advance clinical outcome especially invasion and metastasis.
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