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| ERCC1、XPD和BRCA1基因多态与晚期非小细胞肺癌患者铂类药物化疗效果的相关性 |
| 苏彤1△,赵立军2△,常文军1,王国萍1,何永超1,孙沁莹2,张宏伟1,李强2,曹广文1* |
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| (1.第二军医大学基础部流行病学教研室,上海 200433;2.第二军医大学长海医院呼吸内科,上海 200433) |
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| 摘要: |
| 目的探讨核苷酸切除修复系统(NER)的3个重要基因切除修复交叉互补基因1(ERCC1)、着色性干皮病基因D(XPD)和乳腺癌易感基因 1(BRCA1)的单核苷酸多态性(SNPs)与晚期非小细胞肺癌(NSCLC)患者铂类药物化疗效果的相关性。方法对124例接受含铂类药物化疗的晚期 NSCLC患者进行临床疗效评价。采用TaqMan探针法对ERCC1 Asn118Asn(rs11615)、XPD Lys751Gln(rs13181)和BRCA1 Ser1613Gly(rs1799966)进行基因型分析。比较不同基因型与铂类药物化疗效果的关系。结果BRCA1 Ser1613Gly遗传多态与铂类药物化疗临床受益显著相关(P=0.014),携带Gly等位基因的患者临床受益率明显高于野生型患者 (P=0.006)。没有发现ERCC1 Asn118Asn和XPD Lys751Gln与临床受益的相关性。这3个基因多态存在一定联合作用,携带变异等位基因(ERCC1 T,XPD Gln和BRCA1 Gly)的数目越多,化疗临床受益率越高(P=0.036)。结论NER系统中的BRCA1 Ser1613Gly遗传多态与晚期NSCLC患者铂类药物化疗临床受益相关,联合分析多个基因的SNPs可能对指导化疗药物的选择更有帮助。 |
| 关键词: 单核苷酸多态性 ERCC1 XPD BRCA1 非小细胞肺癌 化疗 |
| DOI：10.3724/SP.J.1008.2010.0117 |
| 投稿时间：2009-09-01修订日期：2009-12-03 |
| 基金项目:上海市登山计划重大课题(06DZ19503). |
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| Relationship of ERCC1,XPD,and BRCA1 polymorphisms with efficacy of platinum-based chemotherapy for patients with advanced non-small cell lung cancer |
| SU Tong1△, ZHAO Li-jun2△, CHANG Wen-jun1, WANG Guo-ping1, HE Yong-chao1, SUN Qin-ying2, ZHANG Hong-wei1, LI Qiang2, CAO Guang-wen1* |
| (1. Department of Epidemiology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China;2. Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China) |
| Abstract: |
| ObjectiveTo investigate the relationship of excision repair cross-complementing 1(ERCC1),xeroderma pigmentosum group D(XPD),and breast cancer susceptibility gene 1(BRCA1) polymorphisms with the efficacy of platinum-based chemotherapy for treatment of the patients with advanced non-small cell lung cancer.MethodsA total of 124 patients with advanced NSCLC were routinely treated with platinum-based chemotherapy,and their clinical responses were evaluated.ERCC1 Asn118Asn(rs11615),XPD Lys751Gln(rs13181) and BRCA1 Ser1613Gly(rs1799966) of the patients were genotyped using the TaqMan method.The association of ERCC1 Asn118Asn,XPD Lys751Gln and BRCA1 Ser1613Gly polymorphisms with the patient responses was analyzed using unconditional logistic regression model.ResultsIt was found that the BRCA1 Ser1613Gly polymorphism was significantly correlated with clinical benefit(P=0.014).Patients carrying Gly allele had better clinical benefit than patients with wildtype allele(P=0.006).No significant association was found between ERCC1 and XPD polymorphisms with clinical benefit.Furthermore,we found that the three SNPs in NER(nucleotide excision repair) could work together.More variant alleles(ERCC1 T,XPD Gln and BRCA1 Gly) was associated with better clinical benefit(P=0.036).ConclusionThe BRCA1 Ser1613Gly polymorphism of NER is associated with the clinical benefit of NSCLC patients receiving platinum-based chemotherapy.Analysis of SNPs of more genes may help to guide drug choosing for chemotherapy. |
| Key words: single nucleotide polymorphism ERCC1 XPD BRCA1 non-small-cell lung cancer chemotherapy |
