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  • Bosse, YohanLaval University,Institut universitaire de cardiologie et de pneumologie de Québec (author)

Transcriptome-wide association study reveals candidate causal genes for lung cancer

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2019-12-09
  • John Wiley & Sons,2020
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-166840
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-166840URI
  • https://doi.org/10.1002/ijc.32771DOI
  • https://lup.lub.lu.se/record/be4adfa3-d184-4211-b54f-78bbcd74c605URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large‐scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome‐wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never‐ and ever‐smokers). We performed replication analysis using lung data from the Genotype‐Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever‐smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E−99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E−6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3‐adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E−5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Li, ZhonglinInstitut universitaire de cardiologie et de pneumologie de Québec,Laval University (author)
  • Xia, JunBaylor College of Medicine (author)
  • Manem, VenkataInstitut universitaire de cardiologie et de pneumologie de Québec,Laval University (author)
  • Carreras-Torres, RobertInternational Agency for Research on Cancer, World Health Organization (author)
  • Gabriel, AurelieInternational Agency for Research on Cancer, World Health Organization (author)
  • Gaudreault, NathalieInstitut universitaire de cardiologie et de pneumologie de Québec,Laval University (author)
  • Albanes, DemetriusNational Cancer Institute, NCI (author)
  • Aldrich, Melinda C.Vanderbilt University Medical Center,Fred Hutchinson Cancer Research Center (author)
  • Andrew, AngelineDartmouth-Hitchcock Medical Center,Radboud University Medical Center (author)
  • Arnold, SusanneUniversity of Kentucky (author)
  • Bickeboeller, HeikeUniversity Medical Center Göttingen (author)
  • Bojesen, Stig E.Copenhagen University Hospital (author)
  • Brennan, PaulInternational Agency for Research on Cancer, World Health Organization (author)
  • Brunnstrom, HansLund University,Lunds universitet,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)med-hsb (author)
  • Caporaso, NeilNational Cancer Institute, NCI (author)
  • Chen, ChuHarvard University (author)
  • Christiani, David C. (author)
  • Field, John K.University of Liverpool (author)
  • Goodman, GarySwedish Medical Center (author)
  • Grankvist, KjellUmeå University,Umeå universitet,Klinisk kemi(Swepub:umu)kjgr0002 (author)
  • Houlston, RichardInstitute of Cancer Research London (author)
  • Johansson, MattiasInternational Agency for Research on Cancer, World Health Organization (author)
  • Johansson, MikaelUmeå University,Umeå universitet,Onkologi(Swepub:umu)mijo0025 (author)
  • Kiemeney, Lambertus A. (author)
  • Lam, StephenBritish Columbia Cancer Agency (author)
  • Landi, Maria T.National Cancer Institute, NCI (author)
  • Lazarus, PhilipWashington State University (author)
  • Le Marchand, LoicUniversity of Hawaii Cancer Center (author)
  • Liu, GeoffreyPrincess Margaret Hospital University of Toronto (author)
  • Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome (author)
  • Rennert, GadiCarmel Medical Center (author)
  • Risch, AngelaUniversity of Salzburg (author)
  • Rosenberg, Susan M.Baylor College of Medicine (author)
  • Schabath, Matthew B.H. Lee Moffitt Cancer Center & Research Institute (author)
  • Shete, SanjayUniversity of Texas (author)
  • Song, ZhuoyiBaylor College of Medicine (author)
  • Stevens, Victoria L.American Cancer Society (author)
  • Tardon, AdoninaUniversity of Oviedo (author)
  • Wichmann, H-ErichHelmholtz Zentrum München (author)
  • Woll, PenellaUniversity of Sheffield (author)
  • Zienolddiny, ShanNational Institute of Occupational Health, Norway (author)
  • Obeidat, Ma'enSt. Paul’s Hospital,University of British Columbia (author)
  • Timens, WimUniversity Medical Center Groningen (author)
  • Hung, Rayjean J.Sinai Health System (author)
  • Joubert, PhilippeInstitut universitaire de cardiologie et de pneumologie de Québec,Laval University (author)
  • Amos, Christopher I.Baylor College of Medicine (author)
  • McKay, James D.International Agency for Research on Cancer, World Health Organization (author)
  • Laval UniversityInstitut universitaire de cardiologie et de pneumologie de Québec (creator_code:org_t)

Related titles

  • In:International Journal of Cancer: John Wiley & Sons146:7, s. 1862-18780020-71361097-0215

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