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Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls.
Wang, Yuzhuo; Gorlova, Olga Y; Gorlov, Ivan P; Zhu, Meng; Dai, Juncheng; Albanes, Demetrius; Lam, Stephen; Tardon, Adonina; Chen, Chu; Goodman, Gary E; Bojesen, Stig E; Landi, Maria Teresa; Johansson, Mattias; Risch, Angela; Wichmann, Heunz-Erich; Bickeboller, Heike; Christiani, David C; Rennert, Gad; Arnold, Susanne M; Brennan, Paul; Field, John K; Shete, Sanjay; Le Marchand, Loïc; Melander, Olle; Brunnstrom, Hans; Liu, Geoffrey; Hung, Rayjean J; Andrew, Angeline S; Kiemeney, Lambertus A; Zienolddiny, Shanbeh; Grankvist, Kjell; Johansson, Mikael; Caporaso, Neil E; Woll, Penella J; Lazarus, Philip; Schabath, Matthew B; Aldrich, Melinda C; Stevens, Victoria L; Ma, Hongxia; Jin, Guangfu; Hu, Zhibin; Amos, Christopher I; Shen, Hongbing.
Afiliação
  • Wang Y; Department of Epidemiology, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
  • Gorlova OY; Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
  • Gorlov IP; Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
  • Zhu M; Department of Medicine, Epidemiology Section, Institute for Clinical and Translational Research, Baylor Medical College, Houston, Texas.
  • Dai J; Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
  • Albanes D; Department of Medicine, Epidemiology Section, Institute for Clinical and Translational Research, Baylor Medical College, Houston, Texas.
  • Lam S; Department of Epidemiology, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
  • Tardon A; Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
  • Chen C; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.
  • Goodman GE; Department of Epidemiology, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
  • Bojesen SE; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.
  • Landi MT; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
  • Johansson M; Department of Integrative Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
  • Risch A; Department of Public Health IUOPA, University of Oviedo, ISPA and CIBERESP, Oviedo, Spain.
  • Wichmann HE; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Bickeboller H; Public Health Sciences Division, Swedish Cancer Institute, Seattle, Washington.
  • Christiani DC; Department of Clinical Biochemistry, Copenhagen University Hospital, Copenhagen, Denmark.
  • Rennert G; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Arnold SM; National Cancer Institute, Bethesda, Maryland.
  • Brennan P; Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
  • Field JK; University of Salzburg, Department of Biosciences, Allergy-Cancer-BioNano Research Centre, Salzburg, Austria.
  • Shete S; Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg, Heidelberg, Germany.
  • Le Marchand L; Translational Lung Research Center Heidelberg (TLRC-H), German Center for Lung Research (DZL), Heidelberg, Germany.
  • Melander O; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig Maximilians University, Munich, Bavaria, Germany.
  • Brunnstrom H; Helmholtz Zentrum Munchen, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.
  • Liu G; Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany.
  • Hung RJ; Department of Genetic Epidemiology, University Medical Center Goettingen, Goettingen, Germany.
  • Andrew AS; Departments of Environmental Health and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • Kiemeney LA; Technion Faculty of Medicine, Carmel Medical Center, Haifa, Israel.
  • Zienolddiny S; Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
  • Grankvist K; Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
  • Johansson M; Molecular and Clinical Cancer Medicine, Roy Castle Lung Cancer Research Programme, The University of Liverpool Institute of Translational Medicine, Liverpool, United Kingdom.
  • Caporaso NE; Department of Epidemiology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
  • Woll PJ; Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, Hawai'i.
  • Lazarus P; Clinical Sciences, Lund University, Lund, Sweden.
  • Schabath MB; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
  • Aldrich MC; Clinical Sciences, Lund University, Lund, Sweden.
  • Stevens VL; Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
  • Ma H; Prosseman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
  • Jin G; Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
  • Hu Z; Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Amos CI; National Institute of Occupational Health (STAMI), Oslo, Norway.
  • Shen H; Department of Medical Biosciences, Umeå University, Umea, Sweden.
Cancer Epidemiol Biomarkers Prev ; 29(7): 1423-1429, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32277007
ABSTRACT

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 × 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 × 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.
Texto completo: Disponível Coleções: Bases de dados internacionais Contexto em Saúde: Agenda de Saúde Sustentável para as Américas / ODS3 - Saúde e Bem-Estar Tema em saúde: Objetivo 9: Redução de doenças não transmissíveis / Meta 3.4: Reduzir as mortes prematuras devido doenças não transmissíveis Base de dados: MEDLINE Tipo de estudo: Estudo observacional / Estudo prognóstico / Fatores de risco Idioma: Inglês Revista: Cancer Epidemiol Biomarkers Prev Assunto da revista: Bioquímica / Epidemiologia / Neoplasias Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China

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Texto completo: Disponível Coleções: Bases de dados internacionais Contexto em Saúde: Agenda de Saúde Sustentável para as Américas / ODS3 - Saúde e Bem-Estar Tema em saúde: Objetivo 9: Redução de doenças não transmissíveis / Meta 3.4: Reduzir as mortes prematuras devido doenças não transmissíveis Base de dados: MEDLINE Tipo de estudo: Estudo observacional / Estudo prognóstico / Fatores de risco Idioma: Inglês Revista: Cancer Epidemiol Biomarkers Prev Assunto da revista: Bioquímica / Epidemiologia / Neoplasias Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China