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 g = 0.57, p = 4.6 × 10 −8 ), breast and ovarian cancer (r g = 0.24, p = 7 × 10 −5 ), breast and lung cancer (r g = 0.18, p =1.5 × 10 −6 ) and breast and colorectal cancer (r g = 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.

Shared heritability and functional enrichment across six solid cancers

Campa D.;
2019-01-01

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 (r g = 0.57, p = 4.6 × 10 −8 ), breast and ovarian cancer (r g = 0.24, p = 7 × 10 −5 ), breast and lung cancer (r g = 0.18, p =1.5 × 10 −6 ) and breast and colorectal cancer (r g = 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.
2019
Jiang, X.; Finucane, H. K.; Schumacher, F. R.; Schmit, S. L.; Tyrer, J. P.; Han, Y.; Michailidou, K.; Lesseur, C.; Kuchenbaecker, K. B.; Dennis, J.; Conti, D. V.; Casey, G.; Gaudet, M. M.; Huyghe, J. R.; Albanes, D.; Aldrich, M. C.; Andrew, A. S.; Andrulis, I. L.; Anton-Culver, H.; Antoniou, A. C.; Antonenkova, N. N.; Arnold, S. M.; Aronson, K. J.; Arun, B. K.; Bandera, E. V.; Barkardottir, R. B.; Barnes, D. R.; Batra, J.; Beckmann, M. W.; Benitez, J.; Benlloch, S.; Berchuck, A.; Berndt, S. I.; Bickeboller, H.; Bien, S. A.; Blomqvist, C.; Boccia, S.; Bogdanova, N. V.; Bojesen, S. E.; Bolla, M. K.; Brauch, H.; Brenner, H.; Brenton, J. D.; Brook, M. N.; Brunet, J.; Brunnstrom, H.; Buchanan, D. D.; Burwinkel, B.; Butzow, R.; Cadoni, G.; Caldes, T.; Caligo, M. A.; Campbell, I.; Campbell, P. T.; Cancel-Tassin, G.; Cannon-Albright, L.; Campa, D.; Caporaso, N.; Carvalho, A. L.; Chan, A. T.; Chang-Claude, J.; Chanock, S. J.; Chen, C.; Christiani, D. C.; Claes, K. B. M.; Claessens, F.; Clements, J.; Collee, J. M.; Correa, M. C.; Couch, F. J.; Cox, A.; Cunningham, J. M.; Cybulski, C.; Czene, K.; Daly, M. B.; Defazio, A.; Devilee, P.; Diez, O.; Gago-Dominguez, M.; Donovan, J. L.; Dork, T.; Duell, E. J.; Dunning, A. M.; Dwek, M.; Eccles, D. M.; Edlund, C. K.; Edwards, D. R. V.; Ellberg, C.; Evans, D. G.; Fasching, P. A.; Ferris, R. L.; Liloglou, T.; Figueiredo, J. C.; Fletcher, O.; Fortner, R. T.; Fostira, F.; Franceschi, S.; Friedman, E.; Gallinger, S. J.; Ganz, P. A.; Garber, J.; Garcia-Saenz, J. A.; Gayther, S. A.; Giles, G. G.; Godwin, A. K.; Goldberg, M. S.; Goldgar, D. E.; Goode, E. L.; Goodman, M. T.; Goodman, G.; Grankvist, K.; Greene, M. H.; Gronberg, H.; Gronwald, J.; Guenel, P.; Hakansson, N.; Hall, P.; Hamann, U.; Hamdy, F. C.; Hamilton, R. J.; Hampe, J.; Haugen, A.; Heitz, F.; Herrero, R.; Hillemanns, P.; Hoffmeister, M.; Hogdall, E.; Hong, Y. -C.; Hopper, J. L.; Houlston, R.; Hulick, P. J.; Hunter, D. J.; Huntsman, D. G.; Idos, G.; Imyanitov, E. N.; Ingles, S. A.; Isaacs, C.; Jakubowska, A.; James, P.; Jenkins, M. A.; Johansson, M.; Johansson, M.; John, E. M.; Joshi, A. D.; Kaneva, R.; Karlan, B. Y.; Kelemen, L. E.; Kuhl, T.; Khaw, K. -T.; Khusnutdinova, E.; Kibel, A. S.; Kiemeney, L. A.; Kim, J.; Kjaer, S. K.; Knight, J. A.; Kogevinas, M.; Kote-Jarai, Z.; Koutros, S.; Kristensen, V. N.; Kupryjanczyk, J.; Lacko, M.; Lam, S.; Lambrechts, D.; Landi, M. T.; Lazarus, P.; Le, N. D.; Lee, E.; Lejbkowicz, F.; Lenz, H. -J.; Leslie, G.; Lessel, D.; Lester, J.; Levine, D. A.; Li, L.; Li, C. I.; Lindblom, A.; Lindor, N. M.; Liu, G.; Loupakis, F.; Lubinski, J.; Maehle, L.; Maier, C.; Mannermaa, A.; Marchand, L. L.; Margolin, S.; May, T.; Mcguffog, L.; Meindl, A.; Middha, P.; Miller, A.; Milne, R. L.; Macinnis, R. J.; Modugno, F.; Montagna, M.; Moreno, V.; Moysich, K. B.; Mucci, L.; Muir, K.; Mulligan, A. M.; Nathanson, K. L.; Neal, D. E.; Ness, A. R.; Neuhausen, S. L.; Nevanlinna, H.; Newcomb, P. A.; Newcomb, L. F.; Nielsen, F. C.; Nikitina-Zake, L.; Nordestgaard, B. G.; Nussbaum, R. L.; Offit, K.; Olah, E.; Olama, A. A. A.; Olopade, O. I.; Olshan, A. F.; Olsson, H.; Osorio, A.; Pandha, H.; Park, J. Y.; Pashayan, N.; Parsons, M. T.; Pejovic, T.; Penney, K. L.; Peters, W. H. M.; Phelan, C. M.; Phipps, A. I.; Plaseska-Karanfilska, D.; Pring, M.; Prokofyeva, D.; Radice, P.; Stefansson, K.; Ramus, S. J.; Raskin, L.; Rennert, G.; Rennert, H. S.; van Rensburg, E. J.; Riggan, M. J.; Risch, H. A.; Risch, A.; Roobol, M. J.; Rosenstein, B. S.; Rossing, M. A.; De Ruyck, K.; Saloustros, E.; Sandler, D. P.; Sawyer, E. J.; Schabath, M. B.; Schleutker, J.; Schmidt, M. K.; Setiawan, V. W.; Shen, H.; Siegel, E. M.; Sieh, W.; Singer, C. F.; Slattery, M. L.; Sorensen, K. D.; Southey, M. C.; Spurdle, A. B.; Stanford, J. L.; Stevens, V. L.; Stintzing, S.; Stone, J.; Sundfeldt, K.; Sutphen, R.; Swerdlow, A. J.; Tajara, E. H.; Tangen, C. M.; Tardon, A.; Taylor, J. A.; Teare, M. D.; Teixeira, M. R.; Terry, M. B.; Terry, K. L.; Thibodeau, S. N.; Thomassen, M.; Bjorge, L.; Tischkowitz, M.; Toland, A. E.; Torres, D.; Townsend, P. A.; Travis, R. C.; Tung, N.; Tworoger, S. S.; Ulrich, C. M.; Usmani, N.; Vachon, C. M.; Van Nieuwenhuysen, E.; Vega, A.; Aguado-Barrera, M. E.; Wang, Q.; Webb, P. M.; Weinberg, C. R.; Weinstein, S.; Weissler, M. C.; Weitzel, J. N.; West, C. M. L.; White, E.; Whittemore, A. S.; Wichmann, H. -E.; Wiklund, F.; Winqvist, R.; Wolk, A.; Woll, P.; Woods, M.; Wu, A. H.; Wu, X.; Yannoukakos, D.; Zheng, W.; Zienolddiny, S.; Ziogas, A.; Zorn, K. K.; Lane, J. M.; Saxena, R.; Thomas, D.; Hung, R. J.; Diergaarde, B.; Mckay, J.; Peters, U.; Hsu, L.; Garcia-Closas, M.; Eeles, R. A.; Chenevix-Trench, G.; Brennan, P. J.; Haiman, C. A.; Simard, J.; Easton, D. F.; Gruber, S. B.; Pharoah, P. D. P.; Price, A. L.; Pasaniuc, B.; Amos, C. I.; Kraft, P.; Lindstrom, S.
File in questo prodotto:
File Dimensione Formato  
Jiang_Nat Com_2019.pdf

accesso aperto

Tipologia: Versione finale editoriale
Licenza: Creative commons
Dimensione 3.83 MB
Formato Adobe PDF
3.83 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/997804
Citazioni
  • ???jsp.display-item.citation.pmc??? 43
  • Scopus 60
  • ???jsp.display-item.citation.isi??? 62
social impact