切除修复交叉互补基因1和乳腺癌易感基因1多态性与非小细胞肺癌对铂类药物化疗敏感性及预后相关性分析

Correlation analysis of ERCC1 and BRCA1 gene polymorphism and non - small cell lung cancer platinum chemotherapy drugs sensitivity and chemotherapy prognosis

目的：对非小细胞肺癌铂类药物化疗患者切除修复交叉互补基因1（ERCC1）和乳腺癌易感基因1（BRCA1）多态性进行研究，探讨 ERCC1和 BRCA1基因多态性与非小细胞肺癌对铂类药物化疗敏感性及化疗预后的相关性。方法选择非小细胞肺癌患者140例为研究对象，所有患者给予含铂类药物化疗，测定外周血 ERCC1和 BRCA1基因，观察 ERCC1 Asn118Asn 基因型和 BRCA1 Ser1613Gly 基因型的分布情况，比较不同基因型和化疗效果及化疗后生存时间的关系。结果 ERCC1 Asn118Asn TT 基因型、CT 基因型和 CC 基因型所占比例分别为5．7％、30．7％和63．6％；BRCA1 Ser1613Gly GG 基因型、AG 基因型和 AA 基因型所占比例分别为8．6％、52．9％和38．6％。140例患者中，完全治愈、部分缓解、疾病稳定和疾病进展者分别为0例、33例、61例和46例，所占比例分别为0．0％、23．6％、43．6％和32．9％，化疗有效率为33．8％。ERCC1 Asn118Asn 基因型和非小细胞肺癌的化疗效果有显著相关性（χ2＝4．416，P ＜0．05）；BRCA1 Ser1613Gly 基因型和非小细胞肺癌的化疗效果有显著相关性（χ2＝13．256，P ＜0．05）。经 Cox 回归分析和 Log-rank test 分析：CC 基因型非小细胞肺癌化疗后的平均生存时间长于 ERCC1 Asn118Asn 基因 CT ＋TT 基因型（OR ＝2．946，χ2＝5．136，P ＜0．05）。BRCA1 Ser1613Gly 基因 AA 基因型非小细胞肺癌化疗后的平均生存时间短于 AG ＋GG 基因型（OR ＝3．124，χ2＝5．136，P ＜0．05）。结论 ERCC1 Asn118Asn 基因型和 BRCA1 Ser1613Gly 基因型与非小细胞肺癌铂类化疗药物敏感性和化疗预后有显著相关性。

Objective To analyze non -small cell lung cancer patients with platinum -based chemotherapy excision repair cross -complementing 1 （ERCC1）and breast cancer susceptibility gene 1 （BRCA1 ）gene polymor-phism,to examine the correlation of ERCC1 and BRCA1 gene polymorphism and non -small cell lung cancer platinum chemotherapy drugs sensitivity and chemotherapy prognosis.Methods 140 cases of non -small cell lung cancer were selected as subjects of this study.All patients were given platnum -based chemotherapy,peripheral blood ERCC1 and BRCA1 genes polymorphism were determined.The distribution of ERCC1 Asn118Asn genotype and BRCA1 Ser1613Gly genotype was observed.The relationship between different genotypes and the effect of chemotherapy and survival time after chemotherapy was compared.Results The proportions of ERCC1 Asn118Asn TT genotype,CT genotype and CC genotype were 5.7%,30.7% and 63.6%.The proportions of BRCA1 Ser1613Gly GG genotype,AG genotype and AA genotype were 8.6%,52.9% and 38.6%.In 140 patients,completely cured,partial response,stable disease and progressive disease patients were 0 case,33 cases,61 cases and 46 cases,the proportions were 0.0%, 23.6%,43.6% and 32.9%,the chemotherapy effective rate was 33.8%.ERCC1 Asn118Asn genotype was signifi-cantly correlated with the effect of non -small cell lung cancer chemotherapy （χ2 =4.416,P 〈0.05 ）.BRCA1 Ser1613Gly genotype was significantly correlated with the effect of non -small cell lung cancer chemotherapy （χ2 =13.256,P 〈0.05）.By Cox regression analysis and Log -rank test analysis,the average survival time of BRCA1 Ser1613Gly gene CC genotype non -small cell lung cancer after chemotherapy was longer than the CT ＋TT genotype （OR =2.946,χ2 =5.136,P 〈0.05）.The average survival time of BRCA1 Ser1613Gly gene AA genotype non -small cell lung cancer after chemotherapy was shorter than the AG ＋GG genotype （OR =3.124,χ2 =5.136,P 〈0.05）.Conclusion ERCC1 Asn118Asn genotype and BRCA1 Ser1613Gly genotype was significantly correlated with non -small cell lung cancer platinum -based chemosensitivity and chemotherapy prognosis.