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Title:
NF-κB1 intronic region polymorphisms as risk factor for head and neck cancer in HPV-infected population from Pakistan

Abstract:
Background: Head and neck cancer (HNC) developed due to the number of risk factors, including infection of Human Papillomavirus (HPV). The genetic predisposition also plays an important role in deregulating the NF-κB pathway, and certain polymorphisms are reported to affect the pathway genes.

Objectives: The present study was conducted for the detection of HPV and polymorphisms in the NF-κB1 gene of HNC patients in the Pakistani population.

Methods: Genomic DNA from HNC tumors samples were extracted using the Exgene SV DNA extraction Kit. Allele-specific PCR and direct sequencing were done for analysis of NF-κB1 SNPs, 94ins/del (rs28362491), rs1598858, and rs4648068.

Results: The genotypes AG (36.2%/ 12%) of rs1598858, and AG (28.3%/ 12%) and GG (28.3%/ 22%) of rs4648068 were associated with significantly (p≤0.05) increased risk of head and neck cancer in studied population. Furthermore, among the HNC cases, genotypes AGrs1598858 (p≤0.014) and GGrs4648068 (p≤0.001) had increased risk of HPV related cancers. Tobacco use (OR-3.158442; [1.140, 8.754]), lymph nodes involvement (OR 4.05128; [1.854, 8.852]), and poorly differentiated tumors (OR 1.997155; [0.940, 4.245]) were positively associated with HPV induced cancers.

Conclusion: It was the first comprehensive study from Pakistan, to evaluate the polymorphic variants of NF-κB1. Genotypes AGrs4648068, GGrs4648068, and AGrs1598858 of NF-κB1 gene are associated with increased risk of head and neck cancers in the Pakistani population. It can be concluded that HPV infection, lymph nodes and tobacco use can act synergetic to each other and add up in modulating HNC when present together with intronic SNPs of NF-κB1 gene.

Journal Title: Current Molecular Medicine

Price: $95


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