Department of Molecular Biology, Genetics Krishna Institute of Medical Sciences, Deemed to Be University Malkapur, Karad Satara, Maharashtra, Pin: 415 539, India.
Department of Oncology, Krishna Institute of Medical Sciences, Karad, India.
Asian Pac J Cancer Prev. 2022 Apr 1;23(4):1291-1300. doi: 10.31557/APJCP.2022.23.4.1291.
Last few years, several studies all over the world revealed the association of DNA repair genes with risk of developing different type of cancers, but were ambiguous to support the evidences in case of cervical cancer risk. These differences in earlier studies directed us to study the association of polymorphisms of BER genes (XRCC1, hOGG1, XPC) and NER genes (XPC, XPD) with cervical cancer susceptibility in the women of rural population of Maharashtra.
The genetic polymorphism in BER and NER pathway genes was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using DNA isolated from intravenous blood samples of patients and normal controls. The study included 400 clinically confirmed cervical cancer patients and 400 healthy women from a tertiary care hospital (Krishna Hospital and Medical Research Centre) of south-western Maharashtra. The association of polymorphisms was confirmed by Odds ratio (OR) with 95% confidence interval.
The single nucleotide polymorphism (SNP) of BER genes including XRCC1, hOGG1 and APE1 were analyzed and the results were noted that 27466AA (OR=4.88; 95% CI: 3.61- 6.60; p<0.0001) and 28152AA (OR=2.89; 95% CI: 1.57- 5.31; p=0.0005) genotypes of XRCC1 (rs25489, rs25487) were significantly associated with cervical cancer risk. The 1245GG genotype of hOGG1 (rs1052133) (OR=45.30; 95% CI: 3.76- 7.46; p=0.001) also showed significant correlation, whereas 2197GG genotype of APE1 (rs1130409) gene showed negative association with cervical carcinogenesis (OR=0.59; 95% CI: 0.35- 0.97; p=0.005). Similarly when we studied SNPs of NER genes including XPC and XPD genes, 21151TT genotype of XPC (rs 2228000) was positively associated with cervical cancer development and 23591AA genotype of XPD (rs1799793) showed negative association (OR=0.34; 95% CI: 0.17- 0.64; p=0.001).
The findings from this study supported that rs25489, rs25487SNPs of XRCC1, rs1052133 of hOGG1 and rs2228000 of XPC may increase cervical cancer risk, whereas rs1130409 SNP of APE1 and rs1799793 SNP of XPD gene lower the risk of cervical cancer in the studied population.
过去几年，全世界的几项研究都揭示了 DNA 修复基因与不同类型癌症风险之间的关联，但在宫颈癌风险方面的证据并不明确。这些早期研究中的差异促使我们研究 BER 基因（XRCC1、hOGG1、XPC）和 NER 基因（XPC、XPD）多态性与马哈拉施特拉邦农村地区女性宫颈癌易感性的关系。
使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法研究 BER 和 NER 途径基因中的遗传多态性，该方法使用来自静脉血样本的 DNA 从马哈拉施特拉邦西南部的一家三级保健医院（Krishna 医院和医学研究中心）的患者和健康女性中进行。使用 95%置信区间的优势比（OR）确认多态性的相关性。
分析了 BER 基因包括 XRCC1、hOGG1 和 APE1 的单核苷酸多态性（SNP），结果表明，27466AA（OR=4.88；95%CI：3.61-6.60；p<0.0001）和 28152AA（OR=2.89；95%CI：1.57-5.31；p=0.0005）基因型的 XRCC1（rs25489、rs25487）与宫颈癌风险显著相关。hOGG1（rs1052133）的 1245GG 基因型（OR=45.30；95%CI：3.76-7.46；p=0.001）也显示出显著相关性，而 APE1（rs1130409）基因的 2197GG 基因型与宫颈癌发生呈负相关（OR=0.59；95%CI：0.35-0.97；p=0.005）。同样，当我们研究 NER 基因包括 XPC 和 XPD 基因的 SNP 时，XPC（rs2228000）的 21151TT 基因型与宫颈癌的发展呈正相关，XPD（rs1799793）的 23591AA 基因型呈负相关（OR=0.34；95%CI：0.17-0.64；p=0.001）。
本研究结果表明，rs25489、rs25487 位点的 XRCC1、rs1052133 位点的 hOGG1 和 rs2228000 位点的 XPC 可能增加宫颈癌风险，而 rs1130409 位点的 APE1 和 rs1799793 位点的 XPD 基因降低了研究人群中宫颈癌的风险。
