Association between a novel regulatory genetic variants and lung cancer risk in Chinese: a two-stage case-control study
10.3760/cma.j.cn112338-20210331-00262
- VernacularTitle:一种新的调控型遗传变异与中国人群肺癌发病风险的关系：两阶段病例-对照研究
- Author:
Xiaoqi ZHU
1
;
Niping SI
;
Xiaoyu FU
;
Jingwen CHENG
;
Na QIN
;
Yichen LIU
;
Tian TIAN
;
Hongxia MA
;
Minjie CHU
Author Information
1. 南通大学公共卫生学院流行病与卫生统计学系 226019
- Keywords:
Lung cancer;
Regulatory quantitative trait loci;
Single nucleotide polymorphism
- From:
Chinese Journal of Epidemiology
2021;42(11):2053-2059
- CountryChina
- Language:Chinese
-
Abstract:
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.
