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Open Access Publications from the University of California

Shared heritability and functional enrichment across six solid cancers

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

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 (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). 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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