Zhang Yanyan, Zhang Zhi, Cao Lei, Lin Jia, Yang Zhenbang, Zhang Xuemei
Institute of Molecular Genetics, College of Life Science, North China University of Science and Technology, Tangshan, China.
Institute of Epidemiology, School of Public Health, North China University of Science and Technology, Tangshan, China.
Oncotarget. 2017 Jan 24;8(4):6216-6221. doi: 10.18632/oncotarget.14053.
CD55, as one of key membrane-bound complement-regulatory proteins (mCRPs), is crucial for the progression of various cancers. This study aims to investigate the role of CD55 variants in the development of non-small cell lung cancer (NSCLC). A case-control study, including 706 lung cancer cases and 706 health controls, was conducted in a Chinese population. The odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression. We found that significantly higher lung cancer risk was linked with CD55 rs2564978 CC genotype (OR = 1.52, 95% CI = 1.11-2.07) or CT genotypes (OR = 1.34, 95% CI = 1.05-1.71), compared to the TT genotype. Stratified analysis showed that rs2564978 CC was associated with NSCLC risk among males (OR = 1.69, 95% CI = 1.14-2.49) and older subjects (OR = 1.75, 95% CI = 1.08-2.82). When stratified by smoking status, the risk effect of rs2564978 CC was more evident among smokers (OR = 2.01, 95% CI = 1.18-3.43) than non-smokers (OR = 1.30, 95% CI = 0.88-1.90). We also conducted the stratified analysis by NSCLC histological types and found that CD55 rs2564978 CC increased the risk of adenocarcinoma with OR (95% CI) of 1.35 (1.01-1.80). The reporter gene expression driven by rs2564978T-containing CD55 promoter was respectively 1.48-fold, 1.96-fold and 1.93-fold higher than those driven by the rs2564978C-containing CD55 promoter in A549, NCI-H2030 and NCI-H23 cells (P = 0.045, 0.010 and < 0.001). These findings indicate that CD55 rs2564978 polymorphism may contribute to an increased risk of NSCLC in Chinese population.
CD55作为关键的膜结合补体调节蛋白（mCRP）之一，对多种癌症的进展至关重要。本研究旨在探讨CD55基因变异在非小细胞肺癌（NSCLC）发生发展中的作用。在中国人群中开展了一项病例对照研究，包括706例肺癌病例和706例健康对照。采用非条件logistic回归估计比值比（OR）和95%置信区间（95%CI）。我们发现，与TT基因型相比，CD55 rs2564978 CC基因型（OR = 1.52，95%CI = 1.11 - 2.07）或CT基因型（OR = 1.34，95%CI = 1.05 - 1.71）与肺癌风险显著升高相关。分层分析显示，rs2564978 CC与男性（OR = 1.69，95%CI = 1.14 - 2.49）和老年受试者（OR = 1.75，95%CI = 1.08 - 2.82）的NSCLC风险相关。按吸烟状况分层时，rs2564978 CC的风险效应在吸烟者中（OR = 2.01，95%CI = 1.18 - 3.43）比非吸烟者中（OR = 1.30，95%CI = 0.88 - 1.90）更明显。我们还按NSCLC组织学类型进行了分层分析，发现CD55 rs2564978 CC使腺癌风险增加，OR（95%CI）为1.35（1.01 - 1.80）。在A549、NCI - H2030和NCI - H23细胞中，由含rs2564978T的CD55启动子驱动的报告基因表达分别比由含rs2564978C的CD55启动子驱动的报告基因表达高1.48倍、1.96倍和1.93倍（P = 0.045、0.010和<0.001）。这些发现表明，CD55 rs2564978多态性可能导致中国人群NSCLC风险增加。
