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Olle Melander

Principal investigator

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

Author

  • Xuemei Ji
  • Hans Brunnström
  • Jonas Manjer
  • Olle Melander
  • Kim Overvad
  • Christopher I. Amos

Summary, in English

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. © 2020, The Author(s).

Department/s

  • LUCC - Lund University Cancer Centre
  • Improved diagnostics and prognostics of lung cancer and metastases to the lungs
  • Surgery
  • EpiHealth: Epidemiology for Health
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Cardiovascular Research - Hypertension

Publishing year

2020

Language

English

Publication/Series

Nature Communications

Volume

11

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics

Keywords

  • allele
  • cancer
  • gene expression
  • genetic analysis
  • health risk
  • heterozygosity
  • mutation
  • tumor

Status

Published

Research group

  • Improved diagnostics and prognostics of lung cancer and metastases to the lungs
  • Surgery
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 2041-1723