尼日利亚拉各斯州肿瘤坏死因子-α基因多态性与宫颈癌的关联
Association between tumour necrosis factor-a polymorphism and cervical cancer in Lagos State, Nigeria.
作者信息
John-Olabode Sarah O, Udenze Ifeoma C, Adejimi Adebola A, Ajie Obiefuna, Okunade Kehinde S
机构信息
Department of Haematology and Blood Transfusion, College of Medicine, University of Lagos, PMB 12003, Lagos, Nigeria.
Department of Clinical Pathology, College of Medicine, University of Lagos, PMB 12003, Lagos, Nigeria.
出版信息
Ecancermedicalscience. 2025 Feb 12;19:1845. doi: 10.3332/ecancer.2025.1845. eCollection 2025.
BACKGROUND
The data on tumour necrosis factor-α (TNF-α) promoter gene polymorphism in the African population are relatively limited, especially in Nigerian women.
OBJECTIVES
This study aimed to determine the prevalence and allele distribution of three TNF-α promoter gene SNPs loci - rs361525 (-238 G>A), rs1799964(-1031 T>C) and rs1800629 (-308 G>A) in women with cervical cancer (CC) and then evaluated the association between TNF-α SNPs and CC among women in Lagos, Nigeria.
METHODS
This is a cross-sectional study of 75 unmatched human immunodeficiency virus (HIV)-infected and uninfected women with and without CC enrolled from October 2021 to January 2023 at the gynaecological oncology, cytology, adult HIV and blood donor clinics of the Lagos University Teaching Hospital. About 5 mL of peripheral blood was collected from each participant for total Deoxyribonucleic acid extraction, primer synthesis and genotyping. The probability of developing CC based on the given SNP genotype was expressed as an odds ratio (OR) with a 95% confidence interval. Allelic frequency deviations from Hardy-Weinberg equilibrium were calculated using chi-square, and the statistical significance level was considered as two-tailed and set at ≤ 0.05.
RESULTS
Our study found that TNF-α -1031 T>C polymorphism was significantly associated with increased CC risk in HIV-negative women (HIV+/CC-; OR = 1.4, 95%CI 0.23-8.42, = 0.03 and HIV-/CC-; OR = 1.37, 95%CI 0.01-1.68, = 0.03) while the -308A>G A allele was also significantly associated with CC in HIV-positive women (OR = 1.33, 95%CI = 0.23-7.75).
CONCLUSION
We observed that HIV-negative and HIV-positive women who carry the C allele of -1031T>C and the A allele of -308G>A promoter gene loci, respectively, are more susceptible to CC. We were also able to show protective linkages for the minor allele of the three SNPs of interest suggesting the potential of TNF-a as a surrogate marker for CC screening in addition to human papillomavirus primary testing. Further studies are required to determine the association between host factors and TNF-a polymorphism to harness the diagnostic and therapeutic advantage these associations will provide in the management of CC.
背景
非洲人群中肿瘤坏死因子-α(TNF-α)启动子基因多态性的数据相对有限,尤其是在尼日利亚女性中。
目的
本研究旨在确定宫颈癌(CC)女性中三个TNF-α启动子基因单核苷酸多态性位点——rs361525(-238 G>A)、rs1799964(-1031 T>C)和rs1800629(-308 G>A)的患病率和等位基因分布,然后评估尼日利亚拉各斯女性中TNF-α单核苷酸多态性与CC之间的关联。
方法
这是一项横断面研究,于2021年10月至2023年1月在拉各斯大学教学医院的妇科肿瘤、细胞学、成人HIV和献血者诊所招募了75名未匹配的感染和未感染人类免疫缺陷病毒(HIV)的女性,她们患有或未患有CC。从每位参与者采集约5 mL外周血用于总脱氧核糖核酸提取、引物合成和基因分型。根据给定的单核苷酸多态性基因型发生CC的概率以比值比(OR)表示,并伴有95%置信区间。使用卡方检验计算偏离哈迪-温伯格平衡的等位基因频率,统计显著性水平被视为双侧,设定为≤0.05。
结果
我们的研究发现,TNF-α -1031 T>C多态性与HIV阴性女性(HIV+/CC-;OR = 1.4,95%CI 0.23 - 8.42,P = 0.03和HIV-/CC-;OR = 1.37,95%CI 0.01 - 1.68,P = 0.03)CC风险增加显著相关,而-308A>G A等位基因在HIV阳性女性中也与CC显著相关(OR = 1.33,95%CI = 0.23 - 7.75)。
结论
我们观察到,分别携带-1031T>C的C等位基因和-/-308G>A启动子基因位点的A等位基因的HIV阴性和HIV阳性女性更容易患CC。我们还能够显示出所关注的三个单核苷酸多态性的次要等位基因的保护关联,这表明除了人乳头瘤病毒初筛外,TNF-α作为CC筛查替代标志物的潜力。需要进一步研究来确定宿主因素与TNF-α多态性之间的关联,以利用这些关联在CC管理中提供的诊断和治疗优势。
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