MGMT（O6-甲基鸟嘌呤-DNA甲基转移酶）基因在修复烷基化剂引起的DNA损伤中起着关键作用，其中包括化疗中使用的烷基化剂。遗传和表观遗传的改变可以影响MGMT基因的调控，进而可能影响子宫颈癌联合化疗放疗（CRT）的治疗反应。本研究旨在评估MGMT基因这些变异与子宫颈癌联合化疗放疗（CRT）的治疗结果之间的相关性。共有460名研究对象（240名对照组和220名患者）通过放大性突变系统-聚合酶链反应（ARMS-PCR）进行MGMT基因变异rs12917（T/C）和rs2308327（A/G）的基因型分析。其中，对照组和患者各48名被分别进行启动子甲基化和表达的甲基化特异性PCR和实时PCR分析。随访了48名患者，评估了治疗（CRT）结果。统计分析使用GraphPad（9.0）和SPSS 18.0版本进行。GG基因型、rs2308327的G等位基因以及两个变异体的'haplotype'为“TA”的个体在子宫颈癌发病率方面显示出显著增加（P≤0.05）。在表观遗传调控中，与对照个体相比，患者的MGMT基因显示出显著高甲基化和表达下调。在CRT的治疗结果中，rs2308327（A/G）基因变体的GG基因型显示出更好的反应，GG+AG与生命状况（存活）显著相关。未甲基化的MGMT基因显示出更好的中位总生存期，与甲基化MGMT启动子相比显著长达25个月。基因变体rs2308327（A/G）和启动子高甲基化调控的MGMT基因可以成为子宫颈癌患者治疗反应的良好预后指标。© 2023年由作者独家授权给德国Springer-Verlag GmbH公司，隶属于Springer Nature出版。

The MGMT (O6-methylguanine-DNA methyltransferase) gene plays a crucial role in repairing DNA damage caused by alkylating agents, including those used in chemotherapy. Genetic and epigenetic alterations can influence the regulation of MGMT gene, which in turn may impact the response to concomitant chemoradiotherapy (CRT) in cervical cancer. The present study was undertaken to evaluate the correlation of such variations in MGMT gene with the treatment outcome of concomitant chemoradiotherapy (CRT) in cervical cancer.A total of 460 study subjects (240 controls and 220 patients) were subjected to genotypic analysis of MGMT gene variants rs12917(T/C) and rs2308327(A/G) by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Out of them, 48 each of controls and patients were analyzed for promoter methylation and expression by methylation-specific PCR and real-time PCR, respectively. Patients (n = 48) were followed up and evaluated for treatment (CRT) outcome. Statistical analyses were done using GraphPad (9.0) and SPSS version 18.0.Individuals with GG genotype, G allele of rs2308327, and haplotype 'TA' of both variants showed a significant increase in the development of cervical cancer (P ≤ 0.05). In epigenetic regulation, there was a significant hypermethylation of MGMT gene and down-regulation of their expression in patients compared to control individuals. In treatment outcome of CRT, GG genotype of rs2308327(A/G) gene variant showed better response and GG + AG was significantly associated with vital status (alive). Unmethylated MGMT gene showed better median overall survival up to 25 months significant in comparison to methylated MGMT promoter.Gene variant rs2308327(A/G) and promoter hypermethylation regulated MGMT gene can be a good prognostic for treatment response in cervical cancer patients.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.