Wu Yi-Liang, Chien Ming-Hsien, Chou Ying-Erh, Chang Jer-Hwa, Liu Tu-Chen, Tsao Thomas Chang-Yao, Chou Ming-Chih, Yang Shun-Fa
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
J Cancer. 2019 Jun 2;10(13):2907-2914. doi: 10.7150/jca.31125. eCollection 2019.
High-mobility group protein box 1 (HMGB1) is overexpressed and reported to be a prognostic factor in patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutants play an important role in NSCLC progression. The aim of this study was to explore potential associations between genetic polymorphisms of and mutations in a cohort that included 280 patients with NSCLC, some of whom were smokers and others who never smoked. Four tagged single-nucleotide polymorphisms (SNPs) of were detected by a TaqMan-based real-time polymerase chain reaction (PCR) in patients. We found that after adjusting for other covariates, NSCLC patients who smoked and who respectively had CG, CT, and TC heterozygotes of rs2249825, rs1045411, and rs1360485, were at lower risk of developing mutant , compared to those patients with wild-type homozygotes. Moreover, significant inverse associations between the CG and CG + GG genotypes of rs2249825 and the hotspot mutation, an exon 19 in-frame deletion, were also observed among NSCLC patients. Within patients harboring mutant , rs1360485 C (TC + CC) allele carriers were at higher risk of developing poorly differentiated cancer types (odds ratio=5.493, 95% confidence interval: 1.130~26.696, =0.019), compared to patients with TT homozygotes. Furthermore, we found that rs1360485 polymorphisms seemed to be related to susceptibility to developing poorly differentiated cancer linked to tobacco consumption in mutant patients. In conclusion, our results suggested that variants are significantly inversely associated with mutations among NSCLC patients who smoked. variants and tobacco consumption might contribute to the pathological development of NSCLC.
高迁移率族蛋白盒1(HMGB1)在非小细胞肺癌(NSCLC)患者中过表达,据报道是一个预后因素。表皮生长因子受体(EGFR)突变在NSCLC进展中起重要作用。本研究的目的是在一个包含280例NSCLC患者的队列中探索[基因名称未给出]基因多态性与[EGFR]突变之间的潜在关联,其中一些患者吸烟,另一些从不吸烟。通过基于TaqMan的实时聚合酶链反应(PCR)检测患者中[基因名称未给出]的四个标签单核苷酸多态性(SNP)。我们发现,在调整其他协变量后,吸烟且分别具有[基因名称未给出]rs2249825、rs1045411和rs1360485的CG、CT和TC杂合子的NSCLC患者,与野生型纯合子患者相比,发生[EGFR]突变的风险较低。此外,在NSCLC患者中还观察到[基因名称未给出]rs2249825的CG和CG + GG基因型与[EGFR]热点突变(外显子19框内缺失)之间存在显著的负相关。在携带[EGFR]突变的患者中,与TT纯合子患者相比,[基因名称未给出]rs1360485 C(TC + CC)等位基因携带者发生低分化癌类型的风险更高(优势比=5.493,95%置信区间:1.130~26.696,P =0.019)。此外,我们发现[基因名称未给出]rs1360485多态性似乎与[EGFR]突变患者中与烟草消费相关的低分化癌易感性有关。总之,我们的结果表明,在吸烟的NSCLC患者中,[基因名称未给出]变体与[EGFR]突变显著负相关。[基因名称未给出]变体和烟草消费可能有助于NSCLC的病理发展。