Systematic analysis of genetic variants in cancer-testis genes identified two novel lung cancer susceptibility loci in Chinese population.

Cancer-testis (CT) genes played important roles in the progression of malignant tumors and were recognized as promising therapeutic targets. However, the roles of genetic variants in CT genes in lung cancer susceptibility have not been well depicted. This study aimed to evaluate the associations between genetic variants in CT genes and lung cancer risk in Chinese population. A total of 22,556 qualified SNPs from 268 lung cancer associated CT genes were initially evaluated based on our previous lung cancer GWAS (Genome-wide association studies) with 2,331 cases and 3,077 controls. As a result, 17 candidate SNPs were further genotyped in 1,056 cases and 1,053 controls using Sequenom platform. Two variants (rs6941653, , T > C, screening: OR = 1.24, 95%CI: 1.12-1.38, = 2.40×10; validation: OR = 1.18, 95%CI: 1.01-1.37, = 0.039 and rs402969, , C > T, screening: OR = 1.15, 95%CI: 1.04-1.26, = 0.006; validation: OR = 1.16, 95%CI: 1.02-1.33, = 0.028) were identified as novel lung cancer susceptibility variants. Stratification analysis indicated that the effect of rs6941653 was stronger in lung squamous cell carcinoma (OR = 1.36) than that in lung adenocarcinoma (OR = 1.15, = 77%, = 0.04). Finally, functional annotations, differential gene expression analysis, pathway and gene ontology analyses were performed to suggest the potential functions of our identified variants and genes. In conclusion, this study identified two novel lung cancer risk variants in Chinese population and provided deeper insight into the roles of CT genes in lung tumorigenesis.