ERCC1核苷酸多态性C118T与中晚期宫颈癌患者顺铂耐药的相关性
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摘要
目的探究ERCC1核苷酸多态性C118T与中晚期宫颈癌患者顺铂耐药间的关系。方法统计诊治的102例中晚期宫颈癌患者顺铂化疗疗效,同时检测患者外周血ERCC1核苷酸多态性C118T比例,将完全缓解+部分缓解定义为化疗敏感组;疾病进展+肿瘤稳定定义为化疗耐药组。比较该多态性与宫颈癌顺铂耐药间的关系。结果纯合子CC型的基因显著存在于化疗敏感组(65%vs 18%)(P <0. 05);两组间杂合子TC型基因分布差异无统计学意义(P> 0. 05);而纯合子TT型基因显著存在于化疗耐药组(67%vs25%)(P <0. 05)。化疗耐药组T等位基因频率显著高于化疗敏感组(74%vs 30%)(P <0. 05);与化疗敏感组相比,TT及TC基因型显著存在于化疗耐药组(OR=8. 438,95%CI=3. 061～23. 256);化疗耐药组T等位基因频率显著高于化疗敏感组(OR=6. 819,95%CI=3. 519～13. 214)。结论 ERCC1核苷酸多态性C118T与中晚期宫颈癌患者顺铂化疗耐药间具有显著联系。
Objective To investigate the correlation between ERCC1 polymorphism C118T and cisplatin resistance in patients with advanced cervical cancer. Methods A total of 102 patients with advanced cervical cancer undergoing cisplatin chemotherapy were recruited. We detected the ERCC1 polymorphism C118T in peripheral blood and collected the follow-up data in these patients. The correlation between ERCC1 polymorphism C118T and cisplatin resistance in advanced cervical cancer was analyzed. Results The homozygous CC genotype was significant higher in chemotherapy sensitive group comparing to the chemotherapy resistant group( 65% vs. 18%,P < 0. 05). The distribution of heterozygous TC genotype showed no significant difference in these two groups,while the homozygous TT genotype was significant higher in chemotherapy resistant group( 67% vs. 25%,P < 0. 05). The frequency of allele C was significantly higher in chemotherapy resistant group than it in chemotherapy sensitive group( 77% vs. 29%,P < 0. 05). At the same time,patients with CC genotype was significantly less in chemotherapy resistant group( OR = 8. 438,95% CI = 3. 061-23. 256) compared to the chemotherapy sensitive group. The frequency of allele T was significantly higher in chemotherapy resistant group than that in chemotherapy sensitive group( OR = 6. 819,95% CI = 3. 519-13. 214). Conclusion ERCC1 polymorphism C118T is associated to the cisplatin resistance in patients with advanced cervical cancer.
Objective To investigate the correlation between ERCC1 polymorphism C118T and cisplatin resistance in patients with advanced cervical cancer. Methods A total of 102 patients with advanced cervical cancer undergoing cisplatin chemotherapy were recruited. We detected the ERCC1 polymorphism C118T in peripheral blood and collected the follow-up data in these patients. The correlation between ERCC1 polymorphism C118T and cisplatin resistance in advanced cervical cancer was analyzed. Results The homozygous CC genotype was significant higher in chemotherapy sensitive group comparing to the chemotherapy resistant group( 65% vs. 18%,P < 0. 05). The distribution of heterozygous TC genotype showed no significant difference in these two groups,while the homozygous TT genotype was significant higher in chemotherapy resistant group( 67% vs. 25%,P < 0. 05). The frequency of allele C was significantly higher in chemotherapy resistant group than it in chemotherapy sensitive group( 77% vs. 29%,P < 0. 05). At the same time,patients with CC genotype was significantly less in chemotherapy resistant group( OR = 8. 438,95% CI = 3. 061-23. 256) compared to the chemotherapy sensitive group. The frequency of allele T was significantly higher in chemotherapy resistant group than that in chemotherapy sensitive group( OR = 6. 819,95% CI = 3. 519-13. 214). Conclusion ERCC1 polymorphism C118T is associated to the cisplatin resistance in patients with advanced cervical cancer.
引文
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[9]Real NE,Castro GN,Dario Cuello-Carrion F,et al. Molecular markers of DNA damage and repair in cervical cancer patients treated with cisplatin neoadjuvant chemotherapy:an exploratory study[J]. Cell Stress Chaperones,2017,22(6):811-822.
[10]Wen Q,Liu Y,Lyu H,et al. Long noncoding rna gas5,which acts as a tumor suppressor via microrna 21,regulates cisplatin resistance expression in cervical cancer[J]. Int J Gynecol Cancer,2017,27(6):1096-1108.
[11]Tao T,Yang X,Qin Q,et al. NHERF1 enhances cisplatin sensitivity in human cervical cancer cells[J]. Int J Mol Sci,2017,18(1):pii:E5.
[12]Hou R,Liu Y,Feng Y,et al. Association of single nucleotide polymorphisms of ERCC1 and XPF with colorectal cancer risk and interaction with tobacco use[J]. Gene,2014,548(1):1-5.
[13]Ryu JS,Viguier J,Praz F. Genetic effect of ERCC1 codon 118polymorphism:and confounding factors[J]. Clin Cancer Res,2006,12(15):4784-4785.
[14]Kaewbubpa W,Areepium N,Sriuranpong V. Effect of the ERCC1(C118T)polymorphism on treatment response in advanced nonsmall cell lung cancer patients undergoing platinum-based chemotherapy[J]. Asian Pac J Cancer Prev,2016,17(11):4917-4920.
[15]Xu ZC,Cai HZ,Li X,et al. ERCC1 C118T polymorphism has predictive value for platinum-based chemotherapy in patients with late-stage bladder cancer[J]. Genet Mol Res,2016,15(2):doi:10. 4238/gmr. 15027801.
[16]Qian YY,Liu XY,Wu Q,et al. The ERCC1 C118T polymorphism predicts clinical outcomes of colorectal cancer patients receiving oxaliplatin-based chemotherapy:a meta-analysis based on 22 studies[J]. Asian Pac J Cancer Prev,2014,15(19):8383-8390.
[17]雄兴东,刘新光. DNA修复基因ERCC1 C19007T多态性与宫颈癌发生的相关性研究[J].实用妇产科杂志,2010,26(4):286-289.
[18]Yu JJ,Lee KB,Mu C,et al. Comparison of two human ovarian carcinoma cell lines(A2780/CP70 and MCAS)that are equally resistant to platinum,but differ at codon 118 of the ERCCC1 gene[J]. Int J Oncol,2000,16(3):555-560.
[19]Cheng J,Ha M,Wang Y,et al. A C118T polymorphism of ERCC1 and response to cisplatin chemotherapy in patients with latestage non-small cell lung cancer[J]. J Cancer Res Clin Oncol,2012,138(2):231-238.
[20]Moxley KM,Benbrook DM,Queimado L,et al. The role of single nucleotide polymorphisms of the ERCC1 and MMS19 genes in predicting platinum-sensitivity,progression-free and overall survival in advanced epithelial ovarian cancer[J]. Gynecol Oncol,2013,130(2):377-382.
[2]Soares S,Nogueira A,Coelho A,et al. Relationship between clinical toxicities and ERCC1 rs3212986 and XRCC3 rs861539polymorphisms in cervical cancer patients[J]. Int J Biol Markers,2018,33(1):116-123.
[3]朱佳妮,王东卓,刘宗唐.宫颈癌筛查技术研究进展[J].中国实用妇科与产科杂志,2016,32(6):597-600.
[4]魏丽惠.从不同视角看以HPV检测作为宫颈癌初筛的方法[J].中国妇产科临床杂志,2016,17(1):1-2.
[5]Zamaniah WW,Mastura M,Phua C,et. al. Definitive concurrent chemoradiotherapy in cervical cancer-a university of malaya medical centre experience[J]. Asian Pac J Cancer Prev,2014,15(20):8987-8992.
[6]Kadkhodayan S,Homaei Shandiz F,Seilanian Toussi M,et al.Concurrent Chemoradiotherapy without Brachytherapy in Locally Advanced Cervical Cancer[J]. Iran J Cancer Prev,2013,6(4):195-200.
[7]韩超,孔为民.单纯放疗与以顺铂为主的同步放化疗治疗子宫颈癌的临床效果对比分析[J].中华妇产科杂志,2007,42(11):723-726.
[8]Park JH,Kim YS,Ahn SD,et al. Concurrent chemoradiotherapy or radiotherapy alone for locally advanced cervical cancer in elderly women[J]. Tumori,2010,96(6):959-965.
[9]Real NE,Castro GN,Dario Cuello-Carrion F,et al. Molecular markers of DNA damage and repair in cervical cancer patients treated with cisplatin neoadjuvant chemotherapy:an exploratory study[J]. Cell Stress Chaperones,2017,22(6):811-822.
[10]Wen Q,Liu Y,Lyu H,et al. Long noncoding rna gas5,which acts as a tumor suppressor via microrna 21,regulates cisplatin resistance expression in cervical cancer[J]. Int J Gynecol Cancer,2017,27(6):1096-1108.
[11]Tao T,Yang X,Qin Q,et al. NHERF1 enhances cisplatin sensitivity in human cervical cancer cells[J]. Int J Mol Sci,2017,18(1):pii:E5.
[12]Hou R,Liu Y,Feng Y,et al. Association of single nucleotide polymorphisms of ERCC1 and XPF with colorectal cancer risk and interaction with tobacco use[J]. Gene,2014,548(1):1-5.
[13]Ryu JS,Viguier J,Praz F. Genetic effect of ERCC1 codon 118polymorphism:and confounding factors[J]. Clin Cancer Res,2006,12(15):4784-4785.
[14]Kaewbubpa W,Areepium N,Sriuranpong V. Effect of the ERCC1(C118T)polymorphism on treatment response in advanced nonsmall cell lung cancer patients undergoing platinum-based chemotherapy[J]. Asian Pac J Cancer Prev,2016,17(11):4917-4920.
[15]Xu ZC,Cai HZ,Li X,et al. ERCC1 C118T polymorphism has predictive value for platinum-based chemotherapy in patients with late-stage bladder cancer[J]. Genet Mol Res,2016,15(2):doi:10. 4238/gmr. 15027801.
[16]Qian YY,Liu XY,Wu Q,et al. The ERCC1 C118T polymorphism predicts clinical outcomes of colorectal cancer patients receiving oxaliplatin-based chemotherapy:a meta-analysis based on 22 studies[J]. Asian Pac J Cancer Prev,2014,15(19):8383-8390.
[17]雄兴东,刘新光. DNA修复基因ERCC1 C19007T多态性与宫颈癌发生的相关性研究[J].实用妇产科杂志,2010,26(4):286-289.
[18]Yu JJ,Lee KB,Mu C,et al. Comparison of two human ovarian carcinoma cell lines(A2780/CP70 and MCAS)that are equally resistant to platinum,but differ at codon 118 of the ERCCC1 gene[J]. Int J Oncol,2000,16(3):555-560.
[19]Cheng J,Ha M,Wang Y,et al. A C118T polymorphism of ERCC1 and response to cisplatin chemotherapy in patients with latestage non-small cell lung cancer[J]. J Cancer Res Clin Oncol,2012,138(2):231-238.
[20]Moxley KM,Benbrook DM,Queimado L,et al. The role of single nucleotide polymorphisms of the ERCC1 and MMS19 genes in predicting platinum-sensitivity,progression-free and overall survival in advanced epithelial ovarian cancer[J]. Gynecol Oncol,2013,130(2):377-382.