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

• Verfasst von: Ji, Xuemei [VerfasserIn]
• Verfasst von: Muley, Thomas [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Titel: Protein-altering germline mutations implicate novel genes related to lung cancer development
• Verf.angabe: Xuemei Ji et al.
• E-Jahr: 2020
• Jahr: 11 May 2020
• Umfang: 14 S.
• Fussnoten: Autoren: Xuemei Ji, Semanti Mukherjee, Maria Teresa Landi, Thomas Muley, Hermann Brenner [und viele weitere] ; Gesehen am 20.10.2020
• Titel Quelle: Enthalten in: Nature Communications
• Ort Quelle: [London] : Nature Publishing Group UK, 2010
• Jahr Quelle: 2020
• Band/Heft Quelle: 11(2020) Artikel-Nummer 2220, 14 Seiten
• ISSN Quelle: 2041-1723
• DOI: doi:10.1038/s41467-020-15905-6
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1736040812

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.