Protein-altering germline mutations implicate novel genes related to lung cancer development



Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga
et al (show 101 more authors) (2020) Protein-altering germline mutations implicate novel genes related to lung cancer development. NATURE COMMUNICATIONS, 11.

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Abstract

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10−15) and replication (adjusted OR = 2.93, P = 2.22 × 10−3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10−22) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk.

Item Type: Article
Uncontrolled Keywords: cancer, computational biology and bioinformatics, genetics
Depositing User: Symplectic Admin
Date Deposited: 21 May 2020 09:06
Last Modified: 06 Oct 2021 12:20
DOI: 10.1038/s41467-020-15905-6
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3088161