Tawe Leabaneng, Grover Surbhi, Zetola Nicola, Robertson Erle S, Gaseitsiwe Simani, Moyo Sikhulile, Kasvosve Ishmael, Paganotti Giacomo M, Narasimhamurthy Mohan
Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana.
Botswana-University of Pennsylvania Partnership, Gaborone, Botswana.
Front Oncol. 2021 Feb 26;11:560296. doi: 10.3389/fonc.2021.560296. eCollection 2021.
Epidemics of human immunodeficiency virus (HIV) and cervical cancer are interconnected. DNA hypermethylation of host genes' promoter in cervical lesions has also been recognized as a contributor to cervical cancer progression. For this purpose we analyzed promoter methylation of four tumor suppressor genes ( and ) and explored their possible association with cervical cancer in Botswana among women of known HIV status. Overall, 228 cervical specimens (128 cervical cancers and 100 non-cancer subjects) were used. Yates-corrected chi-square test and Fisher's exact test were used to explore the association of promoter methylation for each host gene and cancer status. Subsequently, a logistic regression analysis was performed to find which factors, HIV status, high risk-HPV genotypes, patient's age and promoter methylation, were associated with the following dependent variables: cancer status, cervical cancer stage and promoter methylation rate. In patients with cervical cancer the rate of promoter methylation observed was greater than 64% in all the genes studied. Analysis also showed a higher risk of cervical cancer according to the increased number of methylated promoter genes (OR = 6.20; 95% CI: 3.66-10.51; < 0.001). methylation showed the strongest association with cervical cancer compared to other genes (OR = 15.25; 95% CI: 6.06-40.0; < 0.001). Cervical cancer and promoter methylation of and genes were associated with increasing age (OR = 1.12; 95% CI: 1.01-1.26; = 0.037 and OR = 1.05; 95% CI: 1.00-1.10; = 0.040). The presence of epigenetic changes at those genes appeared to be independent of HIV status among subjects with cervical cancer. Moreover, we found that cervical cancer stage was influenced by (χ= 7.32; = 0.002) and (χ=12.68; = 0.013) hypermethylation, and HIV status (χ= 19.93; = 0.001). This study confirms the association between invasive cervical cancer and promoter gene methylation of tumor suppressing genes at the site of cancer. HIV infection did not show any association to methylation changes in this group of cervical cancer patients from Botswana. Further studies are needed to better understand the role of HIV in methylation of host genes among cancer subjects leading to cervical cancer progression.
人类免疫缺陷病毒（HIV）流行与宫颈癌相互关联。宫颈病变中宿主基因启动子的DNA高甲基化也被认为是宫颈癌进展的一个因素。为此，我们分析了四个肿瘤抑制基因（和）的启动子甲基化情况，并在博茨瓦纳已知HIV感染状况的女性中探讨了它们与宫颈癌的可能关联。总体而言，共使用了228份宫颈标本（128例宫颈癌患者和100例非癌症受试者）。采用Yates校正卡方检验和Fisher精确检验来探讨每个宿主基因启动子甲基化与癌症状态之间的关联。随后，进行逻辑回归分析，以确定哪些因素，即HIV感染状况、高危型HPV基因型、患者年龄和启动子甲基化，与以下因变量相关：癌症状态、宫颈癌分期和启动子甲基化率。在宫颈癌患者中，所有研究基因中观察到的启动子甲基化率均大于64%。分析还表明，随着甲基化启动子基因数量的增加，患宫颈癌的风险更高（OR = 6.20；95%CI：3.66 - 10.51；< 0.001）。与其他基因相比，甲基化与宫颈癌的关联最强（OR = 15.25；95%CI：6.06 - 40.0；< 0.001）。宫颈癌以及和基因的启动子甲基化与年龄增长相关（OR = 1.12；95%CI：1.01 - 1.26；= 0.037和OR = 1.05；95%CI：1.00 - 1.10；= 0.040）。在宫颈癌患者中，这些基因的表观遗传变化似乎与HIV感染状况无关。此外，我们发现宫颈癌分期受（χ = 7.32；= 0.002）和（χ = 12.68；= 0.013）高甲基化以及HIV感染状况（χ = 19.93；= 0.001）的影响。这项研究证实了浸润性宫颈癌与癌灶处肿瘤抑制基因启动子基因甲基化之间的关联。在博茨瓦纳的这组宫颈癌患者中，HIV感染与甲基化变化无任何关联。需要进一步研究以更好地了解HIV在癌症患者宿主基因甲基化中导致宫颈癌进展的作用。
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