[Association between a novel regulatory genetic variants and lung cancer risk in Chinese: a two-stage case-control study].

Objective: Regulatory quantitative trait loci (regQTL) theory can help to evaluate the regulation function of single nucleotide polymorphisms (SNPs) on crucial biological signals from a three-dimensional perspective. The aim of this study was to investigate the effect of these regQTL-SNPs on the susceptibility of lung cancer. Methods: Based on the regQTL theory, using the database of identified lung cancer regQTL-SNPs, we screened the SNPs that may function as regQTL in the reported susceptible regions of lung cancer by genome-wide association study(GWAS), and a two-stage case-control study was conducted (screening stage: 2 331 lung cancer cases and 3 077 healthy controls; validation stage: 626 lung cancer cases and 667 healthy controls) to definite the association of related regQTL-SNPs with the susceptibility of lung cancer. Results: A total of 8 regQTL-SNPs were screened in the reported susceptible regions of lung cancer by GWAS. Among which, 3 SNPs were significantly associated with the risk of lung cancer ( P <0.05) in the screening stage. Further validation results indicated that the variant T allele of rs6998591 in ADRA1A was significantly associated with increased risk of lung cancer (additive model: OR =1.33, 95% CI :1.01-1.74, P =0.040). In addition, the variant G allele of rs11202916 in ACTA2 was significantly associated with decreased risk of lung cancer (recessive model: OR =0.71, 95% CI :0.52-0.96, P =0.026). Stratified analysis indicated that the variant T allele of rs6998591 significantly increased lung squamous cell carcinoma risk (additive model: OR =1.53, 95% CI : 1.01-2.32, P =0.043), while the variant G allele of rs11202916 significantly decreased lung adenocarcinoma risk (additive model: OR =0.83, 95% CI : 0.69-0.98, P =0.031). Gene-environment interaction analysis indicated that the risk of developing lung cancer increased by 235% in smoking individuals carrying rs6998591 variant T allele compared with those non-smoking individuals carrying no rs6998591 variant T allele( OR =3.35,95% CI :2.10-5.34, P <0.001). Conclusion: There are two regQTL-SNPs that could significantly affect the susceptibility of lung cancer in the GWAS reported susceptible regions of lung cancer.