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高级别鳞状上皮内病变或宫颈癌与宫颈细胞学阴性之间白细胞介素-10基因启动子多态性及单倍型的比较

Comparison of IL-10 gene promoter polymorphisms and haplotypes between high-grade squamous intraepithelial lesions or cervical cancer and negative cervical cytology.

作者信息

de Souza Amaxsell Thiago Barros, de Sousa Santos Deborah Luisa, Medeiros Fernanda Silva, de Carvalho Kleyton Thiago Costa, Lira George Alexandre, Cobucci Ricardo Ney, de Lima Kassio Michell Gomes, Lucena-Silva Norma, Donadi Eduardo Antônio, de Oliveira Crispim Janaina Cristiana

机构信息

Postgraduate Program in Science Applied to Women's Health, Federal University of Rio Grande do Norte, Natal, 59012-310, RN, Brazil.

Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, 59072- 970, RN, Brazil.

出版信息

Sci Rep. 2025 Aug 3;15(1):28330. doi: 10.1038/s41598-025-12851-5.

Abstract

Cervical cancer, a leading cancer among women, is strongly associated with Human Papillomavirus infection, but host genetic factors also contribute to the progression from high-grade squamous intraepithelial lesions (HSIL) to invasive cancer. Interleukin-10 (IL-10), an immunosuppressive cytokine, may influence susceptibility to HSIL and cervical cancer through genetic variations. This study aimed to compare IL-10 gene promoter polymorphisms, -1082 A > G and - 819T > C, in women diagnosed with HSIL or cervical cancer and those with negative for intraepithelial lesion or malignancy (NILM). In this case-control study, 309 women were analyzed, including 142 with HSIL or cervical cancer and 167 controls with NILM. Blood samples were collected for DNA extraction and genotyping of polymorphisms through PCR amplification. Statistical analyses included comparisons of genotype and allele frequencies, haplotype frequency, and assessments of Hardy-Weinberg equilibrium and linkage disequilibrium. The mean age was 33.4 years for cases and 41.7 years for controls (p < 0.05). For the - 1082 A > G polymorphism, the GG genotype was significantly associated with a decreased risk of HSIL and cervical cancer (p = 0.0266, OR = 0.35). Recessive model (GG vs. AA + AG) confirmed this association (p = 0.0045, OR = 0.29). AC/GC diplotype was associated with a 2-fold increased risk of cervical lesions. Further studies are needed to confirm our results.

摘要

宫颈癌是女性主要的癌症之一,与人类乳头瘤病毒感染密切相关,但宿主遗传因素也在高级别鳞状上皮内病变(HSIL)向浸润性癌的进展过程中发挥作用。白细胞介素-10(IL-10)是一种免疫抑制细胞因子,可能通过基因变异影响HSIL和宫颈癌的易感性。本研究旨在比较诊断为HSIL或宫颈癌的女性与上皮内病变或恶性肿瘤阴性(NILM)的女性中IL-10基因启动子多态性,即-1082 A>G和-819T>C。在这项病例对照研究中,分析了309名女性,包括142名患有HSIL或宫颈癌的女性和167名NILM对照。采集血样进行DNA提取,并通过PCR扩增对多态性进行基因分型。统计分析包括基因型和等位基因频率比较、单倍型频率以及哈迪-温伯格平衡和连锁不平衡评估。病例组的平均年龄为33.4岁,对照组为41.7岁(p<0.05)。对于-1082 A>G多态性,GG基因型与HSIL和宫颈癌风险降低显著相关(p=0.0266,OR=0.35)。隐性模型(GG与AA+AG)证实了这种关联(p=0.0045,OR=0.29)。AC/GC双倍型与宫颈病变风险增加2倍相关。需要进一步研究来证实我们的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d03e/12319095/715183056682/41598_2025_12851_Fig1_HTML.jpg

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