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多态性XRCC6(Ku70)/XRCC7(DNA-PKcs)基因对接受铂类双药化疗的肺癌患者易感性和预后的作用。

Role of polymorphic XRCC6 (Ku70)/XRCC7 (DNA-PKcs) genes towards susceptibility and prognosis of lung cancer patients undergoing platinum based doublet chemotherapy.

作者信息

Singh Amrita, Singh Navneet, Behera Digambar, Sharma Siddharth

机构信息

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

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

出版信息

Mol Biol Rep. 2018 Jun;45(3):253-261. doi: 10.1007/s11033-018-4158-z. Epub 2018 Feb 3.

DOI:10.1007/s11033-018-4158-z
PMID:29397516
Abstract

The DNA repair genes XRCC6 and XRCC7 formed an integral part of double strand break repair (DSBR) pathway. The two genes are thought to play an important role in the repair of lethal double strand damage on DNA. Polymorphic DSBR genes are studied to effect genomic stability. We intend to explore the association of DSBR genes i.e. XRCC6 and XRCC7 with susceptibility and survival in North Indian lung cancer patients. DNA isolation and genotyping was done for 320 controls and 330 lung cancer cases enrolled in the study. Each and every lung cancer study subjects were made a telephonic call and were followed for their health after administration of chemotherapy. Statistical analysis for susceptibility was done using logistic regression analysis. Survival analysis was done using Kaplan-Meier followed by Cox-regression. Small cell lung cancer (SCLC) subtype posed an amplified risk towards lung cancer in case of XRCC7 6721G>T (OR = 4.11, p = 0.0040). Gene-environment interaction analysis revealed that non-smokers with heterozygous genotype (CG) in case of XRCC6 61C>G showed a strong protective effect (OR = 0.38, p = 0.01) towards lung cancer. Survival analysis revealed poor prognosis in case of XRCC6 61C>G SCLC subtype. XRCC6 and XRCC7 were not involved in overall susceptibility and survival. However, in case of XRCC7 6721G>T subjects with SCLC subtype showed an increased susceptibility while poor prognosis in case of XRCC6 61C>G.

摘要

DNA修复基因XRCC6和XRCC7是双链断裂修复(DSBR)途径的重要组成部分。这两个基因被认为在修复DNA上的致死性双链损伤中发挥重要作用。对多态性DSBR基因进行研究以影响基因组稳定性。我们打算探讨DSBR基因即XRCC6和XRCC7与北印度肺癌患者易感性和生存率之间的关联。对纳入该研究的320名对照者和330例肺癌患者进行了DNA分离和基因分型。对每一位肺癌研究对象进行电话随访,并在给予化疗后跟踪其健康状况。使用逻辑回归分析进行易感性的统计分析。使用Kaplan-Meier法进行生存分析,随后进行Cox回归分析。在XRCC7 6721G>T的情况下,小细胞肺癌(SCLC)亚型对肺癌构成更高风险(OR = 4.11,p = 0.0040)。基因-环境相互作用分析显示,在XRCC6 61C>G的情况下,具有杂合基因型(CG)的非吸烟者对肺癌显示出强烈的保护作用(OR = 0.38,p = 0.01)。生存分析显示,XRCC6 61C>G的SCLC亚型预后较差。XRCC6和XRCC7与总体易感性和生存率无关。然而,在XRCC7 6721G>T的情况下,SCLC亚型的受试者易感性增加,而在XRCC6 61C>G的情况下预后较差。

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