Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

Abstract

SummaryWhile several lung cancer susceptibility loci have been identified, much of lung cancer heritability remains unexplained. Here, 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated GWAS analysis of lung cancer on 29,266 patients and 56,450 controls. We identified 18 susceptibility loci achieving genome wide significance, including 10 novel loci. The novel loci highlighted the striking heterogeneity in genetic susceptibility across lung cancer histological subtypes, with four loci associated with lung cancer overall and six with lung adenocarcinoma. Gene expression quantitative trait analysis (eQTL) in 1,425 normal lung tissues highlighted RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes, OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.

Genome-Wide Association Studies in Glioma

“…98; rs4938573) and lung adenocarcinoma (ref. 99; rs1056562), which appear to represent distinct signals (LD metrics with respect to rs12803321: r 2 = 0.04/0.03, D′ = 0.55/0.24, respectively).…”

“…40; rs6062509), lung adenocarcinoma (ref. 99; rs41309931), and colorectal cancer (ref. 54; rs4925386).…”

Genetic modifiers of radon-induced lung cancer risk: a genome-wide interaction study in former uranium miners

“…We conducted a genome-wide gene-radon interaction analysis on LC using data of 28599 samples from 27 studies in men and women of European descent. Although heterogeneity in genetic susceptibility across histological subtypes of LC was demonstrated, the informative sample (n=463 miners, comprising 49 exposed LC cases) is too small to stratify the analysis by histological subtypes or by smoking behaviour (McKay et al 2017). We performed three types of analyses: single-marker and multi-marker interaction analyses and gene-set enrichment analysis on top of the latter.…”

“…The participating studies of TRICL/ILCCO are individually described in the supplement of McKay et al (2017), Table 1 and Supplementary Table I (Online Resource 1). The LC cases of the BfS sample collection were recruited for a study investigating indoor-radon exposure between 1990 und 1997 (Brüske-Hohlfeld et al 2006).…”

Diagnostic and Prognostic Potential of Circulating Long Non-Coding RNAs in Non Small Cell Lung Cancer

“…Lung cancer is a heterogeneous disease featuring field defects in the airway [60]. Most lung cancer patients present the symptoms of cough and expectoration.…”