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

By J. Mckay, R. J. Hung, Younghun Han, Xuchen Zong, R. Carreras-Torres, David C. Christiani, N. Caporaso, M. Johansson, Xiangjun Xiao, Yafang Li and 130 more. Nature Genetics, 2017

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Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer 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 genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights 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.

Subfields: Cancer Research, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7cdb8e53156908f60ff66a09d7d103915172b3db

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Citations in the corpus

• Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2018, background): “Interestingly, while four of the latter were associated with overall lung cancer risk, six were associated with lung adenocarcinoma only [20].”
• Cancer Progress and Priorities: Lung Cancer (2019, background): “GWA studies have successfully identified genetic factors significantly associated with lung cancer susceptibility with varying strengths of association evidence and some loci havebeen refined to specific subgroups, including sex, ethnicity, smoking status, and histologic subtypes (138, 139).”