NF-κB1 内含子区域多态性作为 HPV 感染人群中亚裔巴基斯坦人头颈部癌症的风险因素。

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

机构信息

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

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

出版信息

Curr Mol Med. 2022;22(1):74-82. doi: 10.2174/1566524021666210302144344.

DOI:10.2174/1566524021666210302144344

PMID:33653249

Abstract

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.

摘要

背景

头颈部癌症（HNC）的发生与多种危险因素有关，包括人乳头瘤病毒（HPV）感染。遗传易感性也在调节包括 NF-KB 途径在内的不同信号通路中起着重要作用。一些多态性被报道会影响 NF-kB 途径基因。

目的

本研究旨在探讨 HPV 与巴基斯坦人群 HNC 患者 NF-KB1（p50）基因多态性的关系。

方法

使用 Exgene SV DNA 提取试剂盒从 HNC 肿瘤样本中提取基因组 DNA。采用等位基因特异性 PCR 和直接测序分析 NF-κB1 SNP94ins/del（rs28362491）、rs1598858 和 rs4648068。

结果

在研究人群中，AGrs1598858、AGrs4648068 和 GGrs4648068 基因型与头颈部癌症的发生风险显著增加相关。此外，携带 AGrs1598858 和 GGrs4648068 基因型的 HNC 病例发生 HPV 相关癌症的风险逐渐增加。启动子区域 SNP94ins/del（rs28362491）在研究人群中未检出。吸烟、淋巴结受累和低分化肿瘤与 HPV 诱导的癌症呈正相关。

结论

这是来自巴基斯坦的首个综合研究，评估了 NF-κB1 的多态性变异。NF-κB1 基因的 AGrs4648068、GGrs4648068 和 AGrs1598858 基因型与研究中 HPV 感染的巴基斯坦人群中头颈部癌症的风险增加相关。可以得出结论，HPV 感染、淋巴结受累和吸烟可能协同作用，在巴基斯坦人群中 NF-κB1 基因内含子 SNP 调节 HPV 诱导的 HNC 中发挥作用。