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Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.

About this Publication
Title
Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
Pubmed ID
27197191 (View this publication on the PubMed website)
Publication
Cancer Res. 2016; Volume 76 (Issue 17): Pages 5103-14
Authors
Fehringer G, Kraft P, Pharoah PD, Eeles RA, Chatterjee N, Schumacher FR, Schildkraut JM, Lindström S, Brennan P, Bickeböller H, Houlston RS, Landi MT, Caporaso N, Risch A, Amin Al Olama A, Berndt SI, Giovannucci EL, Grönberg H, Kote-Jarai Z, Ma J, ...show more Muir K, Stampfer MJ, Stevens VL, Wiklund F, Willett WC, Goode EL, Permuth JB, Risch HA, Reid BM, Bezieau S, Brenner H, Chan AT, Chang-Claude J, Hudson TJ, Kocarnik JK, Newcomb PA, Schoen RE, Slattery ML, White E, Adank MA, Ahsan H, Aittomäki K, Baglietto L, Blomquist C, Canzian F, Czene K, Dos-Santos-Silva I, Eliassen AH, Figueroa JD, Flesch-Janys D, Fletcher O, Garcia-Closas M, Gaudet MM, Johnson N, Hall P, Hazra A, Hein R, Hofman A, Hopper JL, Irwanto A, Johansson M, Kaaks R, Kibriya MG, Lichtner P, Liu J, Lund E, Makalic E, Meindl A, Müller-Myhsok B, Muranen TA, Nevanlinna H, Peeters PH, Peto J, Prentice RL, Rahman N, Sanchez MJ, Schmidt DF, Schmutzler RK, Southey MC, Tamimi R, Travis RC, Turnbull C, Uitterlinden AG, Wang Z, Whittemore AS, Yang XR, Zheng W, Buchanan DD, Casey G, Conti DV, Edlund CK, Gallinger S, Haile RW, Jenkins M, Le Marchand L, Li L, Lindor NM, Schmit SL, Thibodeau SN, Woods MO, Rafnar T, Gudmundsson J, Stacey SN, Stefansson K, Sulem P, Chen YA, Tyrer JP, Christiani DC, Wei Y, Shen H, Hu Z, Shu XO, Shiraishi K, Takahashi A, Bossé Y, Obeidat M, Nickle D, Timens W, Freedman ML, Li Q, Seminara D, Chanock SJ, Gong J, Peters U, Gruber SB, Amos CI, Sellers TA, Easton DF, Hunter DJ, Haiman CA, Henderson BE, Hung RJ, Ovarian Cancer Association Consortium (OCAC), PRACTICAL Consortium, Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Colorectal Transdisciplinary (CORECT) Study, African American Breast Cancer Consortium (AABC) and African Ancestry Prostate Cancer Consortium (AAPC)
Affiliations
  • Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.
  • Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • University of Cambridge, Cambridge, United Kingdom.
  • Institute of Cancer Research, London, United Kingdom.
  • National Cancer Instititute, Bethesda, Maryland.
  • University of Southern California, Los Angeles, California.
  • University of Virginia, Charlottesville, Virginia.
  • International Agency for Research on Cancer, Lyon, France.
  • University of Göttingen, Medical School, Göttingen, Germany.
  • Division of Cancer Genetics/Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria. Division of Epigenomics and Cancer Risk Factors, DKFZ - German Cancer Research Center, Heidelberg, Germany. Translational Lung Research Center Heidelberg (TLRC-H), German Center for Lung Research (DZL), Heidelberg, Germany.
...show more
  • Cambridge University, Cambridge, United Kingdom.
  • Karolinska Institutet, Stockholm, Sweden.
  • Harvard Medical School, Boston Massachusetts. Brigham and Women's Hospital, Boston, Massachusetts.
  • University of Manchester, Manchester, United Kingdom. The University of Warwick, Coventry, United Kingdom.
  • Harvard Medical School, Boston Massachusetts.
  • Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
  • Mayo Clinic, Rochester, Minnesota.
  • Moffitt Cancer Center, Tampa, Florida.
  • Yale School of Public Health, New Haven, Connecticut.
  • Service de Génétique Médicale, Nantes, France.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Massachusetts General Hospital, Boston, Massachusetts.
  • National Center for Tumor Diseases and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Ontario Institute for Cancer Research, Toronto, Ontario.
  • Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
  • University of Utah Health Sciences Center, Salt Lake City, Utah.
  • VU University Medical Center, Amsterdam, the Netherlands.
  • University of Chicago, Chicago, Illinois.
  • University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
  • The University of Melbourne, Melbourne, Victoria, Australia.
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
  • Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Harvard Medical School, Boston Massachusetts.
  • University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Breakthrough Research Centre, The Institute of Cancer Research, London, United Kingdom.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Germany. Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany.
  • Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
  • Melbourne School of Population Health, University of Melbourne, Melbourne, Victoria, Australia.
  • Genome Institute of Singapore, Singapore.
  • International Agency for Research on Cancer, Lyon, France. Department of Biobank Research, Umea University, Umea, Sweden.
  • German Research Center for Environmental Health, Neuherberg, Germany.
  • Institute of Community Medicine, UiT The Arctic University of Norway, Tromso, Norway.
  • Technische Universität München, Munich, Germany.
  • Max Planck Institute of Psychiatry, Munich, Germany.
  • Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands.
  • Institute of Cancer Research, Sutton, United Kingdom.
  • Escuela Andaluza de Salud Publica, Instituto de Investigacion Biosanitaria ibs. GRANADA, Granada, Spain. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. CIBER de Epidemiología y Salud Pública CIBERESP, Madrid, Spain.
  • University of Cologne, Cologne, Germany.
  • Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
  • Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
  • Stanford University, Stanford, California.
  • Vanderbilt University, Nashville, Tennessee.
  • Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
  • Case Comprehensive Cancer Center and Mary Ann Swetland Center for Environmental Health, Case Western Reserve University, Cleveland, Ohio.
  • Mayo Clinic, Scottsdale, Arizona.
  • Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
  • deCODE genetics, Amgen, Reykjavik, Iceland.
  • Nanjing Medical University School of Public Health, Nanjing, China.
  • Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
  • Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Department of Molecular Medicine, Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Québec, Canada.
  • University of British Columbia Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, Canada.
  • Merck & Co, Merck Research Laboratories, Seattle, Washington.
  • University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the Netherlands.
  • Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Xiamen University, Xiamen, China.
  • Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
  • Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada. rayjean.hung@lunenfeld.ca.
Abstract

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR.

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