Anoushirvani Ali Arash, Aghabozorgi Reza, Ahmadi Azam, Arjomandzadegan Mohammad, Khalili Sara, Sahraei Maryam, Fereydouni Taha, Khademi Zoha
Internal Medicine, Arak University of Medical Sciences, Arak, IRN.
Genetics, Arak University of Medical Sciences, Arak, IRN.
Cureus. 2019 Apr 10;11(4):e4423. doi: 10.7759/cureus.4423.
Background The nucleotide excision repair (NER) system is one of the most important deoxyribonucleic acid (DNA) repair mechanisms and is critical for chemotherapy resistance. We conducted the present study to investigate the association between two polymorphisms of excision of repair cross-complementing group 1 (ERCC1), the key component of the NER pathway, and the clinicopathological features of patients with non-small cell lung cancer (NSCLC). Methods A total of 38 patients with confirmed NSCLC were included in our study. DNA was extracted from peripheral blood. ERCC1 rs3212986 (8092) and rs11615 (118) were genotyped using molecular assays including polymerase chain reaction (PCR) with restriction fragment length polymorphism (by MboII and HpyCH4 enzymes) and sequencing. Results The PCR results indicated the correct performance of the genomics extraction and molecular protocols. The distribution of C/C, C/A and A/A genotypes at position 8092 was 42.10%, 47.36%, and 10.52% respectively (P=0.03). Multivariate regression analysis showed that there was a significant correlation between C8092A (rs3212986) polymorphism and metastasis, grade of the tumor, and response to treatment. Individuals carrying the rs3212986 CA genotype and A allele had a significantly worse response to the treatment. Also, the correlation between alteration at this genomics location and patients with NSCLC who used to smoke cigarettes was positive. However, no significant association was detected between rs11615 C118>T polymorphism and demographic characteristics of patients with NSCLC. Conclusion We concluded that in lung cancer patients there is a relationship between tumor stage and rs3212986C>A polymorphism.
背景 核苷酸切除修复（NER）系统是最重要的脱氧核糖核酸（DNA）修复机制之一，对化疗耐药性至关重要。我们开展本研究以探究NER途径的关键组成部分——修复交叉互补组1（ERCC1）的两个多态性与非小细胞肺癌（NSCLC）患者临床病理特征之间的关联。方法 本研究共纳入38例确诊为NSCLC的患者。从外周血中提取DNA。使用包括聚合酶链反应（PCR）及限制性片段长度多态性分析（通过MboII和HpyCH4酶）和测序在内的分子检测方法对ERCC1 rs3212986（8092）和rs11615（118）进行基因分型。结果 PCR结果表明基因组提取和分子检测方法操作正确。8092位点C/C、C/A和A/A基因型分布分别为42.10%、47.36%和10.52%（P=0.03）。多因素回归分析显示，C8092A（rs3212986）多态性与转移、肿瘤分级及治疗反应之间存在显著相关性。携带rs3212986 CA基因型和A等位基因的个体对治疗反应明显较差。此外，该基因组位置的改变与曾经吸烟的NSCLC患者之间呈正相关。然而，未检测到rs11615 C118>T多态性与NSCLC患者人口统计学特征之间存在显著关联。结论 我们得出结论，肺癌患者中肿瘤分期与rs3212986C>A多态性之间存在关联。
