Shared heritability and functional enrichment across six solid cancers.

Authors:
Xia Jiang Hilary K Finucane Fredrick R Schumacher Stephanie L Schmit Jonathan P Tyrer Younghun Han Kyriaki Michailidou Corina Lesseur Karoline B Kuchenbaecker Joe Dennis David V Conti Graham Casey Mia M Gaudet Jeroen R Huyghe Demetrius Albanes Melinda C Aldrich Angeline S Andrew Irene L Andrulis Hoda Anton-Culver Antonis C Antoniou Natalia N Antonenkova Susanne M Arnold Kristan J Aronson Banu K Arun Elisa V Bandera Rosa B Barkardottir Daniel R Barnes Jyotsna Batra Matthias W Beckmann Javier Benitez Sara Benlloch Andrew Berchuck Sonja I Berndt Heike Bickeböller Stephanie A Bien Carl Blomqvist Stefania Boccia Natalia V Bogdanova Stig E Bojesen Manjeet K Bolla Hiltrud Brauch Hermann Brenner James D Brenton Mark N Brook Joan Brunet Hans Brunnström Daniel D Buchanan Barbara Burwinkel Ralf Butzow Gabriella Cadoni Trinidad Caldés Maria A Caligo Ian Campbell Peter T Campbell Géraldine Cancel-Tassin Lisa Cannon-Albright Daniele Campa Neil Caporaso André L Carvalho Andrew T Chan Jenny Chang-Claude Stephen J Chanock Chu Chen David C Christiani Kathleen B M Claes Frank Claessens Judith Clements J Margriet Collée Marcia Cruz Correa Fergus J Couch Angela Cox Julie M Cunningham Cezary Cybulski Kamila Czene Mary B Daly Anna deFazio Peter Devilee Orland Diez Manuela Gago-Dominguez Jenny L Donovan Thilo Dörk Eric J Duell Alison M Dunning Miriam Dwek Diana M Eccles Christopher K Edlund Digna R Velez Edwards Carolina Ellberg D Gareth Evans Peter A Fasching Robert L Ferris Triantafillos Liloglou Jane C Figueiredo Olivia Fletcher Renée T Fortner Florentia Fostira Silvia Franceschi Eitan Friedman Steven J Gallinger Patricia A Ganz Judy Garber José A García-Sáenz Simon A Gayther Graham G Giles Andrew K Godwin Mark S Goldberg David E Goldgar Ellen L Goode Marc T Goodman Gary Goodman Kjell Grankvist Mark H Greene Henrik Gronberg Jacek Gronwald Pascal Guénel Niclas Håkansson Per Hall Ute Hamann Freddie C Hamdy Robert J Hamilton Jochen Hampe Aage Haugen Florian Heitz Rolando Herrero Peter Hillemanns Michael Hoffmeister Estrid Høgdall Yun-Chul Hong John L Hopper Richard Houlston Peter J Hulick David J Hunter David G Huntsman Gregory Idos Evgeny N Imyanitov Sue Ann Ingles Claudine Isaacs Anna Jakubowska Paul James Mark A Jenkins Mattias Johansson Mikael Johansson Esther M John Amit D Joshi Radka Kaneva Beth Y Karlan Linda E Kelemen Tabea Kühl Kay-Tee Khaw Elza Khusnutdinova Adam S Kibel Lambertus A Kiemeney Jeri Kim Susanne K Kjaer Julia A Knight Manolis Kogevinas Zsofia Kote-Jarai Stella Koutros Vessela N Kristensen Jolanta Kupryjanczyk Martin Lacko Stephan Lam Diether Lambrechts Maria Teresa Landi Philip Lazarus Nhu D Le Eunjung Lee Flavio Lejbkowicz Heinz-Josef Lenz Goska Leslie Davor Lessel Jenny Lester Douglas A Levine Li Li Christopher I Li Annika Lindblom Noralane M Lindor Geoffrey Liu Fotios Loupakis Jan Lubiński Lovise Maehle Christiane Maier Arto Mannermaa Loic Le Marchand Sara Margolin Taymaa May Lesley McGuffog Alfons Meindl Pooja Middha Austin Miller Roger L Milne Robert J MacInnis Francesmary Modugno Marco Montagna Victor Moreno Kirsten B Moysich Lorelei Mucci Kenneth Muir Anna Marie Mulligan Katherine L Nathanson David E Neal Andrew R Ness Susan L Neuhausen Heli Nevanlinna Polly A Newcomb Lisa F Newcomb Finn Cilius Nielsen Liene Nikitina-Zake Børge G Nordestgaard Robert L Nussbaum Kenneth Offit Edith Olah Ali Amin Al Olama Olufunmilayo I Olopade Andrew F Olshan Håkan Olsson Ana Osorio Hardev Pandha Jong Y Park Nora Pashayan Michael T Parsons Tanja Pejovic Kathryn L Penney Wilbert H M Peters Catherine M Phelan Amanda I Phipps Dijana Plaseska-Karanfilska Miranda Pring Darya Prokofyeva Paolo Radice Kari Stefansson Susan J Ramus Leon Raskin Gad Rennert Hedy S Rennert Elizabeth J van Rensburg Marjorie J Riggan Harvey A Risch Angela Risch Monique J Roobol Barry S Rosenstein Mary Anne Rossing Kim De Ruyck Emmanouil Saloustros Dale P Sandler Elinor J Sawyer Matthew B Schabath Johanna Schleutker Marjanka K Schmidt V Wendy Setiawan Hongbing Shen Erin M Siegel Weiva Sieh Christian F Singer Martha L Slattery Karina Dalsgaard Sorensen Melissa C Southey Amanda B Spurdle Janet L Stanford Victoria L Stevens Sebastian Stintzing Jennifer Stone Karin Sundfeldt Rebecca Sutphen Anthony J Swerdlow Eloiza H Tajara Catherine M Tangen Adonina Tardon Jack A Taylor M Dawn Teare Manuel R Teixeira Mary Beth Terry Kathryn L Terry Stephen N Thibodeau Mads Thomassen Line Bjørge Marc Tischkowitz Amanda E Toland Diana Torres Paul A Townsend Ruth C Travis Nadine Tung Shelley S Tworoger Cornelia M Ulrich Nawaid Usmani Celine M Vachon Els Van Nieuwenhuysen Ana Vega Miguel Elías Aguado-Barrera Qin Wang Penelope M Webb Clarice R Weinberg Stephanie Weinstein Mark C Weissler Jeffrey N Weitzel Catharine M L West Emily White Alice S Whittemore H-Erich Wichmann Fredrik Wiklund Robert Winqvist Alicja Wolk Penella Woll Michael Woods Anna H Wu Xifeng Wu Drakoulis Yannoukakos Wei Zheng Shanbeh Zienolddiny Argyrios Ziogas Kristin K Zorn Jacqueline M Lane Richa Saxena Duncan Thomas Rayjean J Hung Brenda Diergaarde James McKay Ulrike Peters Li Hsu Montserrat García-Closas Rosalind A Eeles Georgia Chenevix-Trench Paul J Brennan Christopher A Haiman Jacques Simard Douglas F Easton Stephen B Gruber Paul D P Pharoah Alkes L Price Bogdan Pasaniuc Christopher I Amos Peter Kraft Sara Lindström

Nat Commun 2019 01 25;10(1):431. Epub 2019 Jan 25.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA, 98109-1024, USA.

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r = 0.57, p = 4.6 × 10), breast and ovarian cancer (r = 0.24, p = 7 × 10), breast and lung cancer (r = 0.18, p =1.5 × 10) and breast and colorectal cancer (r = 0.15, p = 1.1 × 10). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

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http://dx.doi.org/10.1038/s41467-018-08054-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347624PMC
January 2019
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10.742 Impact Factor

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