Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco, Pernambuco, Brazil.
Academic Unit of Serra Talhada - Federal Rural University of Pernambuco, Pernambuco, Brazil.
Cytokine. 2019 Jan;113:99-104. doi: 10.1016/j.cyto.2018.06.014. Epub 2018 Jun 20.
Human papillomavirus (HPV) is responsible for high-grade cervical lesions and cervical cancer. The inflammation plays a key role in cervical cancer progression. In this context, studies propose an association between TNFα and IL10 SNPs and susceptibility to HPV infection. The present work aimed to investigate the possible association between IL10 and TNFα promoter polymorphisms and HPV infection in the cervical carcinogenesis risk in women from Brazil. A total of 654 samples was evaluated in this study. HPV detection was performed by PCR and HPV genotyping was performed by PCR and sequencing of positive MY09/11 PCR product. Genotyping of IL10 SNPs (rs1800871 and rs1800896) was performed by High Resolution Melt analysis. Genotyping of TNFα SNP (rs1800629) was performed by fluorogenic allele-specific probes. The distribution of TNF-308 (rs1800629) allelic (p = 0.03) and genotype (p = 0.03) frequencies and HPV-58 infection has showed a statistically significant difference between case and control groups for the assessed TNFα polymorphism. When it comes to TNFα (rs1800629) allelic and genotypic distribution and HPVs 18 and 31 infections, no statistically significant differences between case and control groups were observed for the studied TNFα polymorphism. The allelic and genotypic distribution of IL10-819 (rs1800871) and IL10-1082 (rs1800896) and HPV infection (HPVs 58, 18 and 31) has showed no statistically significant differences between case and control groups for the assessed IL10 polymorphisms. Furthermore, it was observed that haplotypes were associated with an increased cervical cancer risk in HPVs 16, 18 and 58-positive women. It was observed that women carrying the GTA and ATG haplotypes had 3.85 and 17.99-fold, respectively, increased cervical cancer susceptibility when infected by HPV-58. In women infected with HPV-16 and HPV-18, statistically significant results in women carrying the GTA and ATA haplotypes was observed. They had a 2.32 and 3.67-fold, respectively, increased cervical cancer susceptibility when infected by these two HPV types. The analysis of the haplotypes distribution in women infected with HPV-31 has showed no statistically significant results. Our study indicates that the association of genetic polymorphism in inflammation-related genes represents a risk to the susceptibility in the development of cervical cancer in women infected by HPVs 16, 18 and 58.
人乳头瘤病毒（HPV）是导致高级别宫颈病变和宫颈癌的原因。炎症在宫颈癌进展中起着关键作用。在这种情况下，研究提出 TNFα 和 IL10 SNPs 与 HPV 感染易感性之间存在关联。本研究旨在探讨巴西女性中 IL10 和 TNFα 启动子多态性与 HPV 感染和宫颈癌发生风险之间的可能关联。本研究共评估了 654 个样本。通过 PCR 检测 HPV，通过 PCR 和对阳性 MY09/11 PCR 产物进行测序进行 HPV 基因分型。通过高分辨率熔解分析对 IL10 SNPs(rs1800871 和 rs1800896)进行基因分型。通过荧光等位基因特异性探针对 TNFα SNP(rs1800629)进行基因分型。TNF-308(rs1800629)等位基因（p=0.03）和基因型（p=0.03）频率的分布在病例组和对照组之间显示出统计学显著差异，与 TNFα 多态性评估有关。当涉及 TNFα(rs1800629)等位基因和基因型分布以及 HPV18 和 31 感染时，与 TNFα 多态性研究相比，病例组和对照组之间未观察到统计学显著差异。IL10-819(rs1800871)和 IL10-1082(rs1800896)的等位基因和基因型分布以及 HPV 感染（HPV58、18 和 31）在病例组和对照组之间未显示出与评估的 IL10 多态性统计学显著差异。此外，还观察到在 HPV16、18 和 58 阳性女性中，单倍型与宫颈癌风险增加相关。观察到携带 GTA 和 ATG 单倍型的女性在感染 HPV-58 时，宫颈癌易感性分别增加了 3.85 倍和 17.99 倍。在感染 HPV-16 和 HPV-18 的女性中，携带 GTA 和 ATA 单倍型的女性宫颈癌易感性分别增加了 2.32 倍和 3.67 倍。感染 HPV-31 的女性的单倍型分布分析未显示出统计学显著结果。我们的研究表明，炎症相关基因遗传多态性的关联代表了 HPV16、18 和 58 感染女性宫颈癌发生易感性的风险。
