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

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Chen, HongjieDepartment of Epidemiology, University of Washington, WA, Seattle, United States (författare)

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

Artikel/kapitelEngelska2021

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Cell Press,2021
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Nummerbeteckningar

LIBRIS-ID:oai:DiVA.org:umu-191266
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-191266URI
https://doi.org/10.1016/j.xhgg.2021.100041DOI

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Språk:engelska
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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 och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
5p15.33 region
cancer
CLPTM1L
fine-mapping
pleiotropy
TERT

Biuppslag (personer, institutioner, konferenser, titlar ...)

Majumdar, ArunabhaDepartment 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 (författare)
Wang, LuDepartment of Environmental and Occupational Health Sciences, University of Washington, WA, Seattle, United States (författare)
Kar, SiddharthaMedical Research Council Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom (författare)
Brown, Kevin M.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Feng, HelianDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, MA, Boston, United States (författare)
Turman, ConstanceDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States (författare)
Dennis, JoeCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (författare)
Easton, DouglasCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (författare)
Michailidou, KyriakiBiostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; Cyprus School of Molecular Medicine, Nicosia, Cyprus (författare)
Simard, JacquesDepartment of Molecular Medicine, Faculty of Medicine, Université Laval and Centre de recherche du CHU de Québec-Université Laval, QC, Québec, Canada (författare)
Bishop, TimothyLeeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom (författare)
Cheng, Iona C.Department of Epidemiology and Biostatistics, University of California at San Francisco, CA, San Francisco, United States (författare)
Huyghe, Jeroen R.Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (författare)
Schmit, Stephanie L.Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, USA, OH, Cleveland, United States (författare)
O'Mara, Tracy A.Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia (författare)
Spurdle, Amanda B.Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia (författare)
Gharahkhani, PuyaStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia (författare)
Schumacher, JohannesCenter for Human Genetics, University Hospital of Marburg, Marburg, Germany (författare)
Jankowski, JanuszCollege 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 (författare)
Gockel, InesDepartment of Visceral, Transplant, Thoracic, and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany (författare)
Bondy, Melissa L.Department of Epidemiology and Population Health, Stanford University, CA, Palo Alto, United States (författare)
Houlston, Richard S.Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom (författare)
Jenkins, Robert B.Department of Laboratory Medicine and Pathology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, MN, Rochester, United States (författare)
Melin, Beatrice S.Umeå universitet,Onkologi(Swepub:umu)bema0010 (författare)
Lesseur, CorinaDepartment 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 (författare)
Ness, Andy R.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 (författare)
Diergaarde, BrendaDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA, Pittsburgh, United States; UPMC Hillman Cancer Center, PA, Pittsburgh, United States (författare)
Olshan, Andrew F.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 (författare)
Amos, Christopher I.Institute for Clinical and Translational Research, Baylor College of Medicine, TX, Houston, United States (författare)
Christiani, David C.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 (författare)
Landi, Maria T.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
McKay, James D.International Agency for Research on Cancer, World Health Organization, Lyon, France (författare)
Brossard, MyriamGenetic 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 (författare)
Iles, Mark M.Leeds Institute for Data Analytics, University of Leeds, Leeds, United Kingdom (författare)
Law, Matthew H.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 (författare)
MacGregor, StuartStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia (författare)
Beesley, JonathanDepartment of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia (författare)
Jones, Michelle R.Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, CA, Los Angeles, United States (författare)
Tyrer, JonathanDepartment of Oncology, University of Cambridge, Cambridge, United Kingdom (författare)
Winham, Stacey J.Department of Health Science Research, Mayo Clinic, MN, Rochester, United States (författare)
Klein, Alison P.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 (författare)
Petersen, GloriaDepartment of Health Science Research, Mayo Clinic, MN, Rochester, United States (författare)
Li, DonghuiDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, TX, Houston, United States (författare)
Wolpin, Brian M.Department of Medical Oncology, Dana Farber Harvard Cancer Center, MA, Boston, United States (författare)
Eeles, Rosalind A.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 (författare)
Haiman, Christopher A.Department of Preventive Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Kote-Jarai, ZsofiaOncogenetics 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 (författare)
Schumacher, Fredrick R.Department of Epidemiology and Biostatistics, Case Western Reserve University, OH, Cleveland, United States; Seidman Cancer Center, University Hospitals, OH, Cleveland, United States (författare)
Brennan, PaulNational 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 (författare)
Chanock, Stephen J.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Gaborieau, ValerieNational 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 (författare)
Purdue, Mark P.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Pharoah, PaulCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (författare)
Hung, Rayjean J.Prosserman Centre for Population Health Research, Lunenfeld-Tanenbuaum Research Institute, Sinai Health System, ON, Toronto, Canada (författare)
Amundadottir, Laufey T.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Kraft, PeterDepartment 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 (författare)
Pasaniuc, BogdanDepartment 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 (författare)
Lindström, SaraDepartment of Epidemiology, University of Washington, WA, Seattle, United States; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (författare)
Department of Epidemiology, University of Washington, WA, Seattle, United StatesDepartment 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 (creator_code:org_t)

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Ingår i:Human Genetics and Genomics Advances: Cell Press2:32666-2477

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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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