| Lung cancer is the leading cause of cancer death worldwide.Genomewide association studies have identified 45 susceptibility loci associated with lung cancer,yet single nucleotide polymorphisms at these loci explain only part of the heritability of lung cancer.The molecular mechanisms underlying these associations remain largely unknown.Currently,there is a widely accepted scientific hypothesis for the pathogenesis of lung cancer: these SNPs may play a role by regulating the expression of their adjacent genes.The aim of this study was to identify genes that may have a causal effect on lung cancer susceptibility through gene expression,based on the published GWAS dataset of 11,348 lung cancers and 15,861 controls in a European population,and to integrate them with two large-scale quantitative trait loci datasets of human normal lung tissue.Meta analysis was conducted to merge public summary data of cis-eQTL from a study(n=1111)and GTEx project public dataset,with the method of using two-sample Mendelian randomization,integration of cis-eQTLs summary data from normal lung tissue in a European population with lung cancer and its histological subtypes from European populations(adenocarcinoma and squamous cell carcinoma)GWAS summary data is analyzed,and five candidate genes were found that shared between lung cancer and its histological subtypes,respectively are "PRPF18","DTNBP","CBX8"," ATG12" and "EPHX2".The result supports a potential causal relationship between gene expression and lung cancer susceptibility.Further exploration of candidate genes will continue to provide new insights into the etiology of lung cancer. |
