A common CD55 rs2564978 variant is associated with the susceptibility of non-small cell lung cancer

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.