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北印度接受铂类化疗的肺癌患者中XPC基因多态性与肺癌风险及其与临床结局的关联

XPC Polymorphism and Risk for Lung Cancer in North Indian Patients Treated with Platinum Based Chemotherapy and Its Association with Clinical Outcomes.

作者信息

Lawania Shweta, Singh Navneet, Behera Digamber, Sharma Siddharth

机构信息

Department of Biotechnology, Thapar University, Punjab, 147002, India.

Department of Pulmonary Medicine, Post Graduate Institute of Medical Education & Research (PGIMER), Sector 14, Chandigarh, India.

出版信息

Pathol Oncol Res. 2018 Apr;24(2):353-366. doi: 10.1007/s12253-017-0252-0. Epub 2017 May 24.

Abstract

Xeroderma pigmentosum complementation group C plays an important role in the human repair system. As reported in previous studies its polymorphism are associated with lung cancer susceptibility. The purpose of this study is to investigate the association of XPC gene with lung cancer susceptibility, overall response and clinical outcomes amongst North Indians. A hospital based study of 370 lung cancer cases and 370 healthy controls was conducted and genotypes were determined using PCR-RFLP assay. Results were assessed using logistic linear regression adjusted for age, sex and smoking status. Survival analysis was conducted using Kaplan-Meier survival analysis and Cox regression analysis. The treatment outcomes of 167 lung cancer patients treated with platinum based chemotherapy were evaluated.The mutant genotypic variant of XPC LysGln has been associated with elevated risk of lung cancer(OR:2.30;95%CI:1.41-3.73;p=0.0007) whereas XPC AlaVal showed a highly protective effect (OR:0.25;95%CI:0.10-0.63;p=0.003). The mutant genotype of XPC LysGln presented a higher risk of developing lung cancer in heavy smokers (OR: 3.71; 95%CI:1.46-9.45; p=0.005). The survival analysis presented that heterozygous genotype showed least survival in comparison with mutant genotype in XPC AlaVal genetic variant whereas no significant association was observed in XPC LysGln. In conclusion, XPC LysGln is associated with significant risk towards the lung cancer whereas on contrary XPC AlaVal shows a protective effect.

摘要

着色性干皮病互补组C在人体修复系统中发挥着重要作用。如先前研究所报道,其多态性与肺癌易感性相关。本研究的目的是调查XPC基因与北印度人肺癌易感性、总体反应和临床结局之间的关联。开展了一项基于医院的研究,纳入370例肺癌患者和370名健康对照,采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)确定基因型。使用经年龄、性别和吸烟状况调整的逻辑线性回归评估结果。采用Kaplan-Meier生存分析和Cox回归分析进行生存分析。评估了167例接受铂类化疗的肺癌患者的治疗结局。XPC LysGln的突变基因型与肺癌风险升高相关(比值比:2.30;95%置信区间:1.41-3.73;p=0.0007),而XPC AlaVal显示出高度保护作用(比值比:0.25;95%置信区间:0.10-0.63;p=0.003)。XPC LysGln的突变基因型在重度吸烟者中患肺癌的风险更高(比值比:3.71;95%置信区间:1.46-9.45;p=0.005)。生存分析表明,在XPC AlaVal基因变异中,杂合基因型与突变基因型相比生存时间最短,而在XPC LysGln中未观察到显著关联。总之,XPC LysGln与肺癌的显著风险相关,而相反,XPC AlaVal显示出保护作用。

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