Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco, Pernambuco, Brazil.
Infect Genet Evol. 2013 Oct;19:32-7. doi: 10.1016/j.meegid.2013.06.016. Epub 2013 Jun 22.
Human Papillomavirus (HPV) infection plays a crucial role in the development of cervical lesions and tumors, however most lesions containing high-risk HPVs do not progress to cervical tumors. Some studies suggest that the use of oral contraceptives may increase the risk of cervical carcinogenesis, but this has not been confirmed by all the studies. Cytokines are important molecules that act in the defense of an organism against viral infections. Several genetic studies have attempted to correlate cytokine polymorphisms with human diseases, including cancer. The significance of IL10 polymorphisms for cancer is that they have both immunosuppressive and antiangiogenic properties. We aimed to investigate the role of promoter polymorphisms in the IL10 gene in women with cervical lesions associated with HPV infection, in the presence of the use of oral contraceptives. Using High Resolution Melt analysis (HRM), we analyzed an SNP -1082A/G and -819C/T in interleukin-10 promoter region in 364 Brazilian women: 171 with cervical lesions and HPV infection, and 193 with normal cytological results and HPV-negative. We observed no significant differences in genotype and allele frequencies in the two loci between patients and healthy controls. Furthermore, in the haplotype analysis of IL10, we found that CA haplotype was significantly more frequent in patients infected with HPV than in the control group (p = 0.0188). We did not find any genotype and allelic association of the IL10 gene polymorphisms between cases and controls. However, in this study, when the HPV-positive patients were stratified according to their use of contraceptives, we found a significant association between the -1082G allele (p = 0.0162) and -1082GG genotype (p = 0.0332) among HPV-infected patients who used oral contraceptives. Our findings suggest that -1082A/G gene polymorphism represents a greater susceptibility to progressive cervical lesions in HPV- infected women who use oral contraceptives.
人乳头瘤病毒（HPV）感染在宫颈病变和肿瘤的发展中起着至关重要的作用，然而，大多数含有高危 HPV 的病变并不进展为宫颈癌。一些研究表明，口服避孕药的使用可能会增加宫颈癌发生的风险，但并非所有研究都证实了这一点。细胞因子是在机体抵抗病毒感染中起重要作用的分子。一些遗传研究试图将细胞因子多态性与人类疾病（包括癌症）相关联。IL10 多态性与癌症的相关性在于其具有免疫抑制和抗血管生成特性。我们旨在研究 HPV 感染相关宫颈病变患者中，白细胞介素 10 基因启动子多态性在口服避孕药使用情况下的作用。我们使用高分辨率熔解分析（HRM）分析了 364 名巴西女性白细胞介素 10 启动子区域的 SNP-1082A/G 和-819C/T：171 名患有宫颈病变和 HPV 感染的患者，193 名细胞学正常且 HPV 阴性的患者。我们未观察到两个基因座的基因型和等位基因频率在患者和健康对照组之间存在显著差异。此外，在 IL10 的单体型分析中，我们发现 HPV 感染患者中 CA 单体型明显比对照组更为常见（p=0.0188）。我们未发现 IL10 基因多态性的任何基因型和等位基因与病例和对照组之间的关联。然而，在这项研究中，当根据 HPV 阳性患者使用避孕药的情况进行分层时，我们发现 HPV 阳性患者中使用口服避孕药的患者中 -1082G 等位基因（p=0.0162）和-1082GG 基因型（p=0.0332）之间存在显著关联。我们的研究结果表明，-1082A/G 基因多态性与使用口服避孕药的 HPV 感染妇女进展性宫颈病变的易感性增加有关。
