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Large-scale cross-cancer fine-mapping of the 5p15.33 region reveals multiple independent signals

Chen, Hongjie (författare)
Department of Epidemiology, University of Washington, WA, Seattle, United States
Majumdar, Arunabha (författare)
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, Los Angeles, United States; Department of Mathematics, Indian Institute of Technology Hyderabad, Kandi, India
Wang, Lu (författare)
Department of Environmental and Occupational Health Sciences, University of Washington, WA, Seattle, United States
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Kar, Siddhartha (författare)
Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
Brown, Kevin M. (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
Feng, Helian (författare)
Department of Biostatistics, Harvard T.H. Chan School of Public Health, MA, Boston, United States
Turman, Constance (författare)
Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States
Dennis, Joe (författare)
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
Easton, Douglas (författare)
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
Michailidou, Kyriaki (författare)
Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; Cyprus School of Molecular Medicine, Nicosia, Cyprus
Simard, Jacques (författare)
Department of Molecular Medicine, Faculty of Medicine, Université Laval and Centre de recherche du CHU de Québec-Université Laval, QC, Québec, Canada
Bishop, Timothy (författare)
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom
Cheng, Iona C. (författare)
Department of Epidemiology and Biostatistics, University of California at San Francisco, CA, San Francisco, United States
Huyghe, Jeroen R. (författare)
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
Schmit, Stephanie L. (författare)
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, USA, OH, Cleveland, United States
O'Mara, Tracy A. (författare)
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
Spurdle, Amanda B. (författare)
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
Gharahkhani, Puya (författare)
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia
Schumacher, Johannes (författare)
Center for Human Genetics, University Hospital of Marburg, Marburg, Germany
Jankowski, Janusz (författare)
College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates; Comprehensive Clinical Trials Unit, University College London, London, United Kingdom
Gockel, Ines (författare)
Department of Visceral, Transplant, Thoracic, and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany
Bondy, Melissa L. (författare)
Department of Epidemiology and Population Health, Stanford University, CA, Palo Alto, United States
Houlston, Richard S. (författare)
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
Jenkins, Robert B. (författare)
Department of Laboratory Medicine and Pathology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, MN, Rochester, United States
Melin, Beatrice S. (författare)
Umeå universitet,Onkologi
Lesseur, Corina (författare)
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, NY, New York, United States; International Agency for Research on Cancer, World Health Organization, Lyon, France
Ness, Andy R. (författare)
National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, United Kingdom; Bristol Dental School, University of Bristol, Bristol, United Kingdom
Diergaarde, Brenda (författare)
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA, Pittsburgh, United States; UPMC Hillman Cancer Center, PA, Pittsburgh, United States
Olshan, Andrew F. (författare)
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, Chapel Hill, United States; UNC Lineberger Comprehensive Cancer Center, NC, Chapel Hill, United States
Amos, Christopher I. (författare)
Institute for Clinical and Translational Research, Baylor College of Medicine, TX, Houston, United States
Christiani, David C. (författare)
Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Department of Environmental Health, Harvard T.H. Chan School of Public Health, MA, Boston, United States
Landi, Maria T. (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
McKay, James D. (författare)
International Agency for Research on Cancer, World Health Organization, Lyon, France
Brossard, Myriam (författare)
Genetic Epidemiology and Functional Genomics of Multifactorial Diseases Team, Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS, Université Paris Descartes, Paris, France; Prosserman Centre for Population Health Research, Lunenfeld-Tanenbuaum Research Institute, Sinai Health System, ON, Toronto, Canada
Iles, Mark M. (författare)
Leeds Institute for Data Analytics, University of Leeds, Leeds, United Kingdom
Law, Matthew H. (författare)
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, QLD, Kelvin Grove, Australia
MacGregor, Stuart (författare)
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia
Beesley, Jonathan (författare)
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
Jones, Michelle R. (författare)
Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, CA, Los Angeles, United States
Tyrer, Jonathan (författare)
Department of Oncology, University of Cambridge, Cambridge, United Kingdom
Winham, Stacey J. (författare)
Department of Health Science Research, Mayo Clinic, MN, Rochester, United States
Klein, Alison P. (författare)
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, MD, Baltimore, United States; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, MD, Baltimore, United States
Petersen, Gloria (författare)
Department of Health Science Research, Mayo Clinic, MN, Rochester, United States
Li, Donghui (författare)
Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, TX, Houston, United States
Wolpin, Brian M. (författare)
Department of Medical Oncology, Dana Farber Harvard Cancer Center, MA, Boston, United States
Eeles, Rosalind A. (författare)
Oncogenetics Team, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom; Cancer Genetics Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom
Haiman, Christopher A. (författare)
Department of Preventive Medicine, University of Southern California, CA, Los Angeles, United States
Kote-Jarai, Zsofia (författare)
Oncogenetics Team, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom; Cancer Genetics Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom
Schumacher, Fredrick R. (författare)
Department of Epidemiology and Biostatistics, Case Western Reserve University, OH, Cleveland, United States; Seidman Cancer Center, University Hospitals, OH, Cleveland, United States
Brennan, Paul (författare)
National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, United Kingdom
Chanock, Stephen J. (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
Gaborieau, Valerie (författare)
National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, United Kingdom
Purdue, Mark P. (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
Pharoah, Paul (författare)
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
Hung, Rayjean J. (författare)
Prosserman Centre for Population Health Research, Lunenfeld-Tanenbuaum Research Institute, Sinai Health System, ON, Toronto, Canada
Amundadottir, Laufey T. (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
Kraft, Peter (författare)
Department of Biostatistics, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States
Pasaniuc, Bogdan (författare)
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, Los Angeles, United States; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, Los Angeles, United States; Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, Los Angeles, United States
Lindström, Sara (författare)
Department of Epidemiology, University of Washington, WA, Seattle, United States; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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 (creator_code:org_t)
Cell Press, 2021
2021
Engelska.
Ingår i: Human Genetics and Genomics Advances. - : Cell Press. - 2666-2477. ; 2:3
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Genome-wide association studies (GWASs) have identified thousands of cancer risk loci revealing many risk regions shared across multiple cancers. Characterizing the cross-cancer shared genetic basis can increase our understanding of global mechanisms of cancer development. In this study, we collected GWAS summary statistics based on up to 375,468 cancer cases and 530,521 controls for fourteen types of cancer, including breast (overall, estrogen receptor [ER]-positive, and ER-negative), colorectal, endometrial, esophageal, glioma, head/neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancer, to characterize the shared genetic basis of cancer risk. We identified thirteen pairs of cancers with statistically significant local genetic correlations across eight distinct genomic regions. Specifically, the 5p15.33 region, harboring the TERT and CLPTM1L genes, showed statistically significant local genetic correlations for multiple cancer pairs. We conducted a cross-cancer fine-mapping of the 5p15.33 region based on eight cancers that showed genome-wide significant associations in this region (ER-negative breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, and prostate cancer). We used an iterative analysis pipeline implementing a subset-based meta-analysis approach based on cancer-specific conditional analyses and identified ten independent cross-cancer associations within this region. For each signal, we conducted cross-cancer fine-mapping to prioritize the most plausible causal variants. Our findings provide a more in-depth understanding of the shared inherited basis across human cancers and expand our knowledge of the 5p15.33 region in carcinogenesis.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

5p15.33 region
cancer
CLPTM1L
fine-mapping
pleiotropy
TERT

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Av författaren/redakt...
Chen, Hongjie
Majumdar, Arunab ...
Wang, Lu
Kar, Siddhartha
Brown, Kevin M.
Feng, Helian
visa fler...
Turman, Constanc ...
Dennis, Joe
Easton, Douglas
Michailidou, Kyr ...
Simard, Jacques
Bishop, Timothy
Cheng, Iona C.
Huyghe, Jeroen R ...
Schmit, Stephani ...
O'Mara, Tracy A.
Spurdle, Amanda ...
Gharahkhani, Puy ...
Schumacher, Joha ...
Jankowski, Janus ...
Gockel, Ines
Bondy, Melissa L ...
Houlston, Richar ...
Jenkins, Robert ...
Melin, Beatrice ...
Lesseur, Corina
Ness, Andy R.
Diergaarde, Bren ...
Olshan, Andrew F ...
Amos, Christophe ...
Christiani, Davi ...
Landi, Maria T.
McKay, James D.
Brossard, Myriam
Iles, Mark M.
Law, Matthew H.
MacGregor, Stuar ...
Beesley, Jonatha ...
Jones, Michelle ...
Tyrer, Jonathan
Winham, Stacey J ...
Klein, Alison P.
Petersen, Gloria
Li, Donghui
Wolpin, Brian M.
Eeles, Rosalind ...
Haiman, Christop ...
Kote-Jarai, Zsof ...
Schumacher, Fred ...
Brennan, Paul
Chanock, Stephen ...
Gaborieau, Valer ...
Purdue, Mark P.
Pharoah, Paul
Hung, Rayjean J.
Amundadottir, La ...
Kraft, Peter
Pasaniuc, Bogdan
Lindström, Sara
visa färre...
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MEDICIN OCH HÄLS ...
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och Cancer och onkol ...
MEDICIN OCH HÄLSOVETENSKAP
MEDICIN OCH HÄLS ...
och Medicinska och f ...
MEDICIN OCH HÄLSOVETENSKAP
MEDICIN OCH HÄLS ...
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