关键词: CYP1A1 CYP2E1 DNA repair gene cervical cancer polymorphisms treatment outcome CYP1A1 CYP2E1 DNA repair gene cervical cancer polymorphisms treatment outcome

Mesh : Case-Control Studies Chemoradiotherapy Cisplatin / therapeutic use Cytochrome P-450 CYP1A1 / genetics Cytochrome P-450 CYP2E1 / genetics Cytochrome P-450 Enzyme System / genetics DNA Repair DNA-Binding Proteins / genetics Female Genetic Predisposition to Disease Genotype Humans Polymorphism, Single Nucleotide Uterine Cervical Neoplasms / drug therapy radiotherapy X-ray Repair Cross Complementing Protein 1 / genetics Case-Control Studies Chemoradiotherapy Cisplatin / therapeutic use Cytochrome P-450 CYP1A1 / genetics therapeutic use Cytochrome P-450 CYP2E1 / genetics DNA Repair / genetics DNA-Binding Proteins / genetics Female Genetic Predisposition to Disease Genotype Humans Polymorphism, Single Nucleotide / genetics Uterine Cervical Neoplasms / drug therapy therapy X-ray Repair Cross Complementing Protein 1 / genetics

来  源:   DOI:10.3389/bjbs.2021.10120   PDF(Pubmed)

Abstract:
Background: Evidences suggest that single nucleotide polymorphisms (SNPs) can be considered as potential biomarkers for disease progression and therapeutic response in cervical cancer. The present study investigated the association of CYP1A1 T>C (rs4646903), CYP1A1 A>G (rs1048943), CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), XRCC1 G>A (rs25487), XRCC2 G>A (rs3218536) and XRCC3 C>T (rs861539) polymorphisms with treatment outcome of cisplatin based chemoradiation (CRT). Methods: Total 227 cervical cancer cases, treated with the same chemoradiotherapy regimen were selected for the study. Genotyping analysis was performed by PCR-restriction fragment length polymorphisms (PCR-RFLP). Treatment response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Association of all clinical data (responses, recurrence and survival of patients) and single nucleotide polymorphisms (SNPs) was analysed by using SPSS (version 21.0). Results: Patients with TA/AA genotype of CYP2E1 T>A polymorphism showed significantly poor response while those with GC/CC genotype of RAD51 G>C showed better response (p = 0.008, p = 0.014 respectively). Death was significantly higher in patients with GG genotypes of RAD51 G>C and XRCC1 G>A (p = 0.006, p = 0.002 respectively). Women with GC+CC genotype of RAD51 G>C and AG+GG of XRCC1 showed better survival and also reduced risk of death (HR = 0.489, p = 0.008; HR = 0.484, p = 0.003 respectively). Conclusion: Results suggested that CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), and XRCC1 G>A (rs25487) polymorphisms may be used as predictive markers for clinical outcomes in cervical cancer patients undergoing cisplatin based concomitant chemoradiotherapy.
摘要:
背景:有证据表明,单核苷酸多态性(SNP)可以被认为是宫颈癌疾病进展和治疗反应的潜在生物标志物。本研究调查了CYP1A1T>C(rs4646903),CYP1A1A>G(rs1048943),CYP2E1T>A(rs6413432),RAD51G>C(rs1801320),XRCC1G>A(rs25487),XRCC2G>A(rs3218536)和XRCC3C>T(rs861539)多态性与基于顺铂的放化疗(CRT)的治疗结果。方法:宫颈癌227例,选择相同的放化疗方案进行研究.通过PCR限制性片段长度多态性(PCR-RFLP)进行基因分型分析。通过实体瘤中的反应评价标准(RECIST)评价治疗反应。所有临床数据的关联(反应,使用SPSS(21.0版)分析患者的复发和生存)和单核苷酸多态性(SNP)。结果:CYP2E1T>A多态性的TA/AA基因型患者的反应明显较差,而RAD51G>C的GC/CC基因型患者的反应较好(分别为p=0.008,p=0.014)。RAD51G>C和XRCC1G>A的GG基因型患者的死亡显着增加(分别为p=0.006,p=0.002)。具有RAD51G>C和XRCC1的AGGG的GCCC基因型的女性显示出更好的生存率,并且还降低了死亡风险(HR=0.489,p=0.008;HR=0.484,p=0.003)。结论:结果表明CYP2E1T>A(rs6413432),RAD51G>C(rs1801320),XRCC1G>A(rs25487)多态性可作为宫颈癌患者顺铂同步放化疗后临床结局的预测指标.
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