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  • Wang, YuzhuoJiangsu Cancer Hospital,Nanjing Medical University (author)

Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • American Association for Cancer Research,2020
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-174057
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-174057URI
  • https://doi.org/10.1158/1055-9965.EPI-19-1085DOI
  • https://lup.lub.lu.se/record/5c0ebc42-b6d3-499c-9949-522efb35506fURI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Background: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.Methods: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data from The Cancer Genome Atlas (TCGA) project.Results: We identified seven independent SNPs in five lung CDGs that were consistently associated with lung cancer risk in discovery (P < 0.001) and validation (P < 0.05) stages. Among these loci, rs78062588 in TPM3 (1q21.3) was a new lung cancer susceptibility locus (OR = 0.86, P = 1.65 x 10(-6)). Subgroup analysis by histologic types further identified nine lung CDGs. Analysis of somatic alterations found that in lung adenocarcinomas, rs78062588[C] allele (TPM3 in 1q21.3) was associated with elevated somatic copy number of TPM3 (OR = 1.16, P = 0.02). In lung adenocarcinomas, rs1611182 (HLA-A in 6p22.1) was associated with truncation mutations of the transcriptional misregulation in cancer pathway (OR = 0.66, P = 1.76 x 10(-3)).Conclusions: Genetic variants can regulate functions of lung CDGs and influence lung cancer susceptibility. Impact: Our findings might help unravel biological mechanisms underlying lung cancer susceptibility.

Subject headings and genre

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  • Gorlova, Olga Y.Baylor College of Medicine,Dartmouth College (author)
  • Gorlov, Ivan P.Dartmouth College,Baylor College of Medicine (author)
  • Zhu, MengNanjing Medical University,Jiangsu Cancer Hospital (author)
  • Dai, JunchengNanjing Medical University (author)
  • Albanes, DemetriusNational Cancer Institute, USA (author)
  • Lam, StephenBritish Columbia Cancer Agency (author)
  • Tardon, AdoninaUniversity of Oviedo (author)
  • Chen, ChuFred Hutchinson Cancer Research Center,Harvard University,Vanderbilt University (author)
  • Goodman, Gary E.Swedish Medical Center (author)
  • Bojesen, Stig E.University of Copenhagen,Copenhagen University Hospital (author)
  • Landi, Maria TeresaNational Cancer Institute, USA (author)
  • Johansson, MattiasInternational Agency for Research on Cancer, World Health Organization (author)
  • Risch, AngelaGerman Cancer Research Centre,University of Salzburg,German Center for Lung Research (DZL) (author)
  • Wichmann, Heunz-ErichLudwig-Maximilian University of Munich,Technical University of Munich,Helmholtz Zentrum München (author)
  • Bickeboller, HeikeUniversity Medical Center Göttingen (author)
  • Christiani, David C. (author)
  • Rennert, GadTechnion - Israel Institute of Technology (author)
  • Arnold, Susanne M.University of Kentucky (author)
  • Brennan, PaulInternational Agency for Research on Cancer, World Health Organization (author)
  • Field, John K.University of Liverpool (author)
  • Shete, SanjayUniversity of Texas MD Anderson Cancer Center,Dartmouth-Hitchcock Medical Center (author)
  • Le Marchand, LoicUniversity of Hawai'i at Hilo (author)
  • Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-ome (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)
  • Liu, GeoffreyPrincess Margaret Hospital University of Toronto (author)
  • Hung, Rayjean J.Sinai Health System (author)
  • Andrew, Angeline S. (author)
  • Kiemeney, Lambertus A.Radboud University Medical Center (author)
  • Zienolddiny, ShanbehNational Institute of Occupational Health, Norway (author)
  • Grankvist, KjellUmeå University,Umeå universitet,Klinisk kemi(Swepub:umu)kjgr0002 (author)
  • Johansson, MikaelUmeå University,Umeå universitet,Onkologi(Swepub:umu)mijo0025 (author)
  • Caporaso, Neil E.National Cancer Institute, USA (author)
  • Woll, Penella J.University of Sheffield (author)
  • Lazarus, PhilipWashington State University (author)
  • Schabath, Matthew B.H. Lee Moffitt Cancer Center & Research Institute (author)
  • Aldrich, Melinda C. (author)
  • Stevens, Victoria L.American Cancer Society (author)
  • Ma, HongxiaNanjing Medical University (author)
  • Jin, GuangfuNanjing Medical University (author)
  • Hu, ZhibinNanjing Medical University (author)
  • Amos, Christopher I.Baylor College of Medicine (author)
  • Shen, HongbingNanjing Medical University (author)
  • Jiangsu Cancer HospitalNanjing Medical University (creator_code:org_t)

Related titles

  • In:Cancer Epidemiology, Biomarkers and Prevention: American Association for Cancer Research29:7, s. 1423-14291055-99651538-7755

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