NF-κB1 Intronic Region Polymorphisms as Risk Factor for Head and Neck Cancer in HPV-Infected Population from Pakistan.


Journal

Current molecular medicine
ISSN: 1875-5666
Titre abrégé: Curr Mol Med
Pays: Netherlands
ID NLM: 101093076

Informations de publication

Date de publication:
2022
Historique:
received: 06 10 2020
revised: 27 01 2021
accepted: 09 02 2021
pubmed: 4 3 2021
medline: 5 4 2022
entrez: 3 3 2021
Statut: ppublish

Résumé

Head and neck cancer (HNC) develops due to a number of risk factors, including infection of Human Papillomavirus (HPV). The genetic predisposition also plays an important role in deregulating different signaling pathways including the NF-KB pathway. Certain polymorphisms are reported to affect the NF-kB pathway genes. The present research was conducted to study the association of HPV with NF-KB1 (p50) gene polymorphisms in HNC patients of the Pakistani population. Genomic DNA from HNC tumors samples was 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. The genotypes AGrs1598858, AGrs4648068 and GGrs4648068 were associated with significantly increased risk of head and neck cancer in studied population. Furthermore the HNC cases with genotypes AGrs1598858 and GGrs4648068 displayed growing risk of HPV related cancers. Promotor region SNP 94ins/del (rs28362491) was not detected in studied population. Tobacco use, lymph nodes involvement and poorly differentiated tumors were positively associated with HPV induced cancers. It is 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 studied HPV infected Pakistani population. It can be concluded that HPV infection, involvement of lymph nodes and tobacco use can act synergetic and add up in modulating HPV induced HNC with intronic SNPs of NF-κB1 gene in Pakistani population.

Sections du résumé

BACKGROUND
Head and neck cancer (HNC) develops due to a number of risk factors, including infection of Human Papillomavirus (HPV). The genetic predisposition also plays an important role in deregulating different signaling pathways including the NF-KB pathway. Certain polymorphisms are reported to affect the NF-kB pathway genes.
OBJECTIVES
The present research was conducted to study the association of HPV with NF-KB1 (p50) gene polymorphisms in HNC patients of the Pakistani population.
METHODS
Genomic DNA from HNC tumors samples was 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 AGrs1598858, AGrs4648068 and GGrs4648068 were associated with significantly increased risk of head and neck cancer in studied population. Furthermore the HNC cases with genotypes AGrs1598858 and GGrs4648068 displayed growing risk of HPV related cancers. Promotor region SNP 94ins/del (rs28362491) was not detected in studied population. Tobacco use, lymph nodes involvement and poorly differentiated tumors were positively associated with HPV induced cancers.
CONCLUSION
It is 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 studied HPV infected Pakistani population. It can be concluded that HPV infection, involvement of lymph nodes and tobacco use can act synergetic and add up in modulating HPV induced HNC with intronic SNPs of NF-κB1 gene in Pakistani population.

Identifiants

pubmed: 33653249
pii: CMM-EPUB-114667
doi: 10.2174/1566524021666210302144344
doi:

Substances chimiques

NF-kappa B p50 Subunit 0
NFKB1 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

74-82

Subventions

Organisme : Higher Education Commission of Pakistan (Indigenous PhD Fellowship)
ID : 2MB1-487

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Sumaira Sarwar (S)

Department of Biochemistry, Quaid-i-Azam University, Islamabad, 75500, Pakistan.

Muammad Usman Tareen (MU)

Department of Biochemistry, Quaid-i-Azam University, Islamabad, 75500, Pakistan.

Maimoona Sabir (M)

Department of Microbiology, University of Haripur, Khyber Pakhtunkhwa 75500, Pakistan.

Aneesa Sultan (A)

Department of Biochemistry, Quaid-i-Azam University, Islamabad, 75500, Pakistan.

Salman A Malik (SA)

Department of Biochemistry, Quaid-i-Azam University, Islamabad, 75500, Pakistan.

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Classifications MeSH