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.

Jiang, X., Finucane, H., Schumacher, F., Schmit, S., Tyrer, J., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K., Dennis, J., Conti, D., Casey, G., Gaudet, M., Huyghe, J., Albanes, D., Aldrich, M., Andrew, A., Andrulis, I., Anton-Culver, H., Antoniou, A., Antonenkova, N., Arnold, S., Aronson, K., Arun, B., Bandera, E., Barkardottir, R., Barnes, D., Batra, J., Beckmann, M., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S., Bickeböller, H., Bien, S., Blomqvist, C., Boccia, S., Bogdanova, N., Bojesen, S., Bolla, M., Brauch, H., Brenner, H., Brenton, J., Brook, M., Brunet, J., Brunnström, H., Buchanan, D., Burwinkel, B., Butzow, R., Cadoni, G., Caldés, T., Caligo, M., Campbell, I., Campbell, P., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A., Chan, A., Chang-Claude, J., Chanock, S., Chen, C., Christiani, D., Claes, K., Claessens, F., Clements, J., Collée, J., Correa, M., Couch, F., Cox, A., Cunningham, J., Cybulski, C., Czene, K., Daly, M., Defazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J., Dörk, T., Duell, E., Dunning, A., Dwek, M., Eccles, D., Edlund, C., Edwards, D., Ellberg, C., Evans, D., Fasching, P., Ferris, R., Liloglou, T., Figueiredo, J., Fletcher, O., Fortner, R., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S., Ganz, P., Garber, J., García-Sáenz, J., Gayther, S., Giles, G., Godwin, A., Goldberg, M., Goldgar, D., Goode, E., Goodman, M., Goodman, G., Grankvist, K., Greene, M., Gronberg, H., Gronwald, J., Guénel, P., Håkansson, N., Hall, P., Hamann, U., Hamdy, F., Hamilton, R., Hampe, J., Haugen, A., Heitz, F., Herrero, R., Hillemanns, P., Hoffmeister, M., Høgdall, E., Hong, Y., Hopper, J., Houlston, R., Hulick, P., Hunter, D., Huntsman, D., Idos, G., Imyanitov, E., Ingles, S., Isaacs, C., Jakubowska, A., James, P., Jenkins, M., Johansson, M., Johansson, M., John, E., Joshi, A., Kaneva, R., Karlan, B., Kelemen, L., Kühl, T., Khaw, K., Khusnutdinova, E., Kibel, A., Kiemeney, L., Kim, J., Kjaer, S., Knight, J., Kogevinas, M., Kote-Jarai, Z., Koutros, S., Kristensen, V., Kupryjanczyk, J., Lacko, M., Lam, S., Lambrechts, D., Landi, M., Lazarus, P., Le, N., Lee, E., Lejbkowicz, F., Lenz, H., Leslie, G., Lessel, D., Lester, J., Levine, D., Li, L., Li, C., Lindblom, A., Lindor, N., Liu, G., Loupakis, F., Lubiński, J., Maehle, L., Maier, C., Mannermaa, A., Marchand, L., Margolin, S., May, T., Mcguffog, L., Meindl, A., Middha, P., Miller, A., Milne, R., Macinnis, R., Modugno, F., Montagna, M., Moreno, V., Moysich, K., Mucci, L., Muir, K., Mulligan, A., Nathanson, K., Neal, D., Ness, A., Neuhausen, S., Nevanlinna, H., Newcomb, P., Newcomb, L., Nielsen, F., Nikitina-Zake, L., Nordestgaard, B., Nussbaum, R., Offit, K., Olah, E., Olama, A., Olopade, O., Olshan, A., Olsson, H., Osorio, A., Pandha, H., Park, J., Pashayan, N., Parsons, M., Pejovic, T., Penney, K., Peters, W., Phelan, C., Phipps, A., Plaseska-Karanfilska, D., Pring, M., Prokofyeva, D., Radice, P., Stefansson, K., Ramus, S., Raskin, L., Rennert, G., Rennert, H., Van Rensburg, E., Riggan, M., Risch, H., Risch, A., Roobol, M., Rosenstein, B., Rossing, M., De Ruyck, K., Saloustros, E., Sandler, D., Sawyer, E., Schabath, M., Schleutker, J., Schmidt, M., Setiawan, V., Shen, H., Siegel, E., Sieh, W., Singer, C., Slattery, M., Sorensen, K., Southey, M., Spurdle, A., Stanford, J., Stevens, V., Stintzing, S., Stone, J., Sundfeldt, K., Sutphen, R., Swerdlow, A., Tajara, E., Tangen, C., Tardon, A., Taylor, J., Teare, M., Teixeira, M., Terry, M., Terry, K., Thibodeau, S., Thomassen, M., Bjørge, L., Tischkowitz, M., Toland, A., Torres, D., Townsend, P., Travis, R., Tung, N., Tworoger, S., Ulrich, C., Usmani, N., Vachon, C., Van Nieuwenhuysen, E., Vega, A., Aguado-Barrera, M., Wang, Q., Webb, P., Weinberg, C., Weinstein, S., Weissler, M., Weitzel, J., West, C., White, E., Whittemore, A., Wichmann, H., Wiklund, F., Winqvist, R., Wolk, A., Woll, P., Woods, M., Wu, A., Wu, X., Yannoukakos, D., Zheng, W., Zienolddiny, S., Ziogas, A., Zorn, K., Lane, J., Saxena, R., Thomas, D., Hung, R., Diergaarde, B., Mckay, J., Peters, U., Hsu, L., García-Closas, M., Eeles, R., Chenevix-Trench, G., Brennan, P., Haiman, C., Simard, J., Easton, D., Gruber, S., Pharoah, P., Price, A., Pasaniuc, B., Amos, C., Kraft, P., Lindström, S., Shared heritability and functional enrichment across six solid cancers., <<NATURE COMMUNICATIONS>>, 2019; 2019 (10): 1-21. [doi:10.1038/s41467-018-08054-4] [http://hdl.handle.net/10807/129871]

Shared heritability and functional enrichment across six solid cancers.

Boccia, Stefania;Cadoni, Gabriella;
2019

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.
2019
Inglese
Jiang, X., Finucane, H., Schumacher, F., Schmit, S., Tyrer, J., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K., Dennis, J., Conti, D., Casey, G., Gaudet, M., Huyghe, J., Albanes, D., Aldrich, M., Andrew, A., Andrulis, I., Anton-Culver, H., Antoniou, A., Antonenkova, N., Arnold, S., Aronson, K., Arun, B., Bandera, E., Barkardottir, R., Barnes, D., Batra, J., Beckmann, M., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S., Bickeböller, H., Bien, S., Blomqvist, C., Boccia, S., Bogdanova, N., Bojesen, S., Bolla, M., Brauch, H., Brenner, H., Brenton, J., Brook, M., Brunet, J., Brunnström, H., Buchanan, D., Burwinkel, B., Butzow, R., Cadoni, G., Caldés, T., Caligo, M., Campbell, I., Campbell, P., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A., Chan, A., Chang-Claude, J., Chanock, S., Chen, C., Christiani, D., Claes, K., Claessens, F., Clements, J., Collée, J., Correa, M., Couch, F., Cox, A., Cunningham, J., Cybulski, C., Czene, K., Daly, M., Defazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J., Dörk, T., Duell, E., Dunning, A., Dwek, M., Eccles, D., Edlund, C., Edwards, D., Ellberg, C., Evans, D., Fasching, P., Ferris, R., Liloglou, T., Figueiredo, J., Fletcher, O., Fortner, R., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S., Ganz, P., Garber, J., García-Sáenz, J., Gayther, S., Giles, G., Godwin, A., Goldberg, M., Goldgar, D., Goode, E., Goodman, M., Goodman, G., Grankvist, K., Greene, M., Gronberg, H., Gronwald, J., Guénel, P., Håkansson, N., Hall, P., Hamann, U., Hamdy, F., Hamilton, R., Hampe, J., Haugen, A., Heitz, F., Herrero, R., Hillemanns, P., Hoffmeister, M., Høgdall, E., Hong, Y., Hopper, J., Houlston, R., Hulick, P., Hunter, D., Huntsman, D., Idos, G., Imyanitov, E., Ingles, S., Isaacs, C., Jakubowska, A., James, P., Jenkins, M., Johansson, M., Johansson, M., John, E., Joshi, A., Kaneva, R., Karlan, B., Kelemen, L., Kühl, T., Khaw, K., Khusnutdinova, E., Kibel, A., Kiemeney, L., Kim, J., Kjaer, S., Knight, J., Kogevinas, M., Kote-Jarai, Z., Koutros, S., Kristensen, V., Kupryjanczyk, J., Lacko, M., Lam, S., Lambrechts, D., Landi, M., Lazarus, P., Le, N., Lee, E., Lejbkowicz, F., Lenz, H., Leslie, G., Lessel, D., Lester, J., Levine, D., Li, L., Li, C., Lindblom, A., Lindor, N., Liu, G., Loupakis, F., Lubiński, J., Maehle, L., Maier, C., Mannermaa, A., Marchand, L., Margolin, S., May, T., Mcguffog, L., Meindl, A., Middha, P., Miller, A., Milne, R., Macinnis, R., Modugno, F., Montagna, M., Moreno, V., Moysich, K., Mucci, L., Muir, K., Mulligan, A., Nathanson, K., Neal, D., Ness, A., Neuhausen, S., Nevanlinna, H., Newcomb, P., Newcomb, L., Nielsen, F., Nikitina-Zake, L., Nordestgaard, B., Nussbaum, R., Offit, K., Olah, E., Olama, A., Olopade, O., Olshan, A., Olsson, H., Osorio, A., Pandha, H., Park, J., Pashayan, N., Parsons, M., Pejovic, T., Penney, K., Peters, W., Phelan, C., Phipps, A., Plaseska-Karanfilska, D., Pring, M., Prokofyeva, D., Radice, P., Stefansson, K., Ramus, S., Raskin, L., Rennert, G., Rennert, H., Van Rensburg, E., Riggan, M., Risch, H., Risch, A., Roobol, M., Rosenstein, B., Rossing, M., De Ruyck, K., Saloustros, E., Sandler, D., Sawyer, E., Schabath, M., Schleutker, J., Schmidt, M., Setiawan, V., Shen, H., Siegel, E., Sieh, W., Singer, C., Slattery, M., Sorensen, K., Southey, M., Spurdle, A., Stanford, J., Stevens, V., Stintzing, S., Stone, J., Sundfeldt, K., Sutphen, R., Swerdlow, A., Tajara, E., Tangen, C., Tardon, A., Taylor, J., Teare, M., Teixeira, M., Terry, M., Terry, K., Thibodeau, S., Thomassen, M., Bjørge, L., Tischkowitz, M., Toland, A., Torres, D., Townsend, P., Travis, R., Tung, N., Tworoger, S., Ulrich, C., Usmani, N., Vachon, C., Van Nieuwenhuysen, E., Vega, A., Aguado-Barrera, M., Wang, Q., Webb, P., Weinberg, C., Weinstein, S., Weissler, M., Weitzel, J., West, C., White, E., Whittemore, A., Wichmann, H., Wiklund, F., Winqvist, R., Wolk, A., Woll, P., Woods, M., Wu, A., Wu, X., Yannoukakos, D., Zheng, W., Zienolddiny, S., Ziogas, A., Zorn, K., Lane, J., Saxena, R., Thomas, D., Hung, R., Diergaarde, B., Mckay, J., Peters, U., Hsu, L., García-Closas, M., Eeles, R., Chenevix-Trench, G., Brennan, P., Haiman, C., Simard, J., Easton, D., Gruber, S., Pharoah, P., Price, A., Pasaniuc, B., Amos, C., Kraft, P., Lindström, S., Shared heritability and functional enrichment across six solid cancers., <<NATURE COMMUNICATIONS>>, 2019; 2019 (10): 1-21. [doi:10.1038/s41467-018-08054-4] [http://hdl.handle.net/10807/129871]
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