Genome-wide association analysis identifies three new breast cancer susceptibility loci

Ghoussaini, M., Fletcher, O., Michailidou, K., Turnbull, C., Schmidt, M.K., Dicks, E., Dennis, J., Wang, Q., Humphreys, M.K., Luccarini, C., Baynes, C., Conroy, D., Maranian, M., Ahmed, S., Driver, K., Johnson, N., Orr, N., Dos Santos Silva, I., Waisfisz, Q., Meijers-Heijboer, H., Uitterlinden, A.G., Rivadeneira, F., Hall, P., Czene, K., Irwanto, A., Liu, J., Nevanlinna, H., Aittomaki, K., Blomqvist, C., Meindl, A., Schmutzler, R.K., Muller-Myhsok, B., Lichtner, P., Chang-Claude, J., Hein, R., Nickels, S., Flesch-Janys, D., Tsimiklis, H., Makalic, E., Schmidt, D., Bui, M., Hopper, J.L., Apicella, C., Park, D.J., Southey, M.C., Hunter, D.J., Channock, S.J., Broeks, A., Verhoef, S., Hogervorst, F.B.L., Fasching, P.A., Lux, M.P., Beckmann, M.W., Ekici, A.B., Sawyer, E., Tomlinson, I., Kerin, M.J., Marme, F., Schneeweiss, A., Sohn, C., Burwinkel, B., Guenel, P., Truong, T., Cordina-Duverger, E., Menegaux, F., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Milne, R.L., Alonso, M.R., Gonzalez-Neira, A., Benitez, J., Anton-Culver, H., Ziogas, A., Bernstein, L., Clarke Dur, C., Brenner, H., Muller, H., Arndt, V., Stegmaier, C., Justenhoven, C., Brauch, H., Brüning, T., Wang-Gohrke, S., Eilber, U., Dörk, T., Schürmann, P., Bremer, M., Hillemanns, P., Bogdanova, N.V., Antonenkova, N.N., Rogov, Y.I., Karstens, J.H., Bermisheva, M., Prokofieva, D., Khusnutdinova, E., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V.-M., Hartikainen, J.M., Lambrechts, D., Yesilyurt, B.T., Floris, G., Leunen, K., Manoukian, S., Bonanni, B., Fortuzzi, S., Peterlongo, P., Couch, F.J., Wang, X., Stevens, K.N., Lee, A., Giles, G.G., Baglietto, L., Severi, G., McLean, C.A., Grenaker Alnaes, G., Kristensen, V., Borrensen-Dale, A.-L., John, E.M., Miron, A., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Kauppila, S., Andrulis, I.L., Glendon, G., Mulligan, A.M., Devilee, P., van Asperen, C.J., Tollenaar, R.A.E.M., Seynaeve, C., Figueroa, J.D., Garcia-Closas, M., Brinton, L., Lissowska, J., Hooning, M.J., Hollestelle, A., Oldenburg, R.A., van den Ouweland, A.M.W., Cox, A., Reed, M.W.R., Shah, M., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Jones, M., Schoemaker, M.J., Ashworth, A., Swerdlow, A.J., Beesley, J., Chen, X., Muir, K., Lophatananon, A., Rattanamongkongul, S., Chaiwerawattana, A., Kang, D., Yoo, K.Y., Noh, D.Y., Shen, C.Y., Yu, J.C., Wu, P.E., Hsiung, C.N., Perkins, A., Swann, R., Velentzis, L.S., Eccles, D.M., Tapper, W.J., Gerty, S.M., Graham, N.J., Ponder, B.A.J., Chenevix-Trench, G., Pharoah, P.D.P., Lathrop, M., Dunning, A.M., Rahman, N., Peto, J. and Easton, D.F. 2012. Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nature Genetics. 44 (3), pp. 312-318.

TitleGenome-wide association analysis identifies three new breast cancer susceptibility loci
AuthorsGhoussaini, M., Fletcher, O., Michailidou, K., Turnbull, C., Schmidt, M.K., Dicks, E., Dennis, J., Wang, Q., Humphreys, M.K., Luccarini, C., Baynes, C., Conroy, D., Maranian, M., Ahmed, S., Driver, K., Johnson, N., Orr, N., Dos Santos Silva, I., Waisfisz, Q., Meijers-Heijboer, H., Uitterlinden, A.G., Rivadeneira, F., Hall, P., Czene, K., Irwanto, A., Liu, J., Nevanlinna, H., Aittomaki, K., Blomqvist, C., Meindl, A., Schmutzler, R.K., Muller-Myhsok, B., Lichtner, P., Chang-Claude, J., Hein, R., Nickels, S., Flesch-Janys, D., Tsimiklis, H., Makalic, E., Schmidt, D., Bui, M., Hopper, J.L., Apicella, C., Park, D.J., Southey, M.C., Hunter, D.J., Channock, S.J., Broeks, A., Verhoef, S., Hogervorst, F.B.L., Fasching, P.A., Lux, M.P., Beckmann, M.W., Ekici, A.B., Sawyer, E., Tomlinson, I., Kerin, M.J., Marme, F., Schneeweiss, A., Sohn, C., Burwinkel, B., Guenel, P., Truong, T., Cordina-Duverger, E., Menegaux, F., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Milne, R.L., Alonso, M.R., Gonzalez-Neira, A., Benitez, J., Anton-Culver, H., Ziogas, A., Bernstein, L., Clarke Dur, C., Brenner, H., Muller, H., Arndt, V., Stegmaier, C., Justenhoven, C., Brauch, H., Brüning, T., Wang-Gohrke, S., Eilber, U., Dörk, T., Schürmann, P., Bremer, M., Hillemanns, P., Bogdanova, N.V., Antonenkova, N.N., Rogov, Y.I., Karstens, J.H., Bermisheva, M., Prokofieva, D., Khusnutdinova, E., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V.-M., Hartikainen, J.M., Lambrechts, D., Yesilyurt, B.T., Floris, G., Leunen, K., Manoukian, S., Bonanni, B., Fortuzzi, S., Peterlongo, P., Couch, F.J., Wang, X., Stevens, K.N., Lee, A., Giles, G.G., Baglietto, L., Severi, G., McLean, C.A., Grenaker Alnaes, G., Kristensen, V., Borrensen-Dale, A.-L., John, E.M., Miron, A., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Kauppila, S., Andrulis, I.L., Glendon, G., Mulligan, A.M., Devilee, P., van Asperen, C.J., Tollenaar, R.A.E.M., Seynaeve, C., Figueroa, J.D., Garcia-Closas, M., Brinton, L., Lissowska, J., Hooning, M.J., Hollestelle, A., Oldenburg, R.A., van den Ouweland, A.M.W., Cox, A., Reed, M.W.R., Shah, M., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Jones, M., Schoemaker, M.J., Ashworth, A., Swerdlow, A.J., Beesley, J., Chen, X., Muir, K., Lophatananon, A., Rattanamongkongul, S., Chaiwerawattana, A., Kang, D., Yoo, K.Y., Noh, D.Y., Shen, C.Y., Yu, J.C., Wu, P.E., Hsiung, C.N., Perkins, A., Swann, R., Velentzis, L.S., Eccles, D.M., Tapper, W.J., Gerty, S.M., Graham, N.J., Ponder, B.A.J., Chenevix-Trench, G., Pharoah, P.D.P., Lathrop, M., Dunning, A.M., Rahman, N., Peto, J. and Easton, D.F.
Abstract

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

JournalNature Genetics
Journal citation44 (3), pp. 312-318
ISSN1546-1718
Year22 Jan 2012
PublisherNature Publishing Group
Digital Object Identifier (DOI)doi:10.1038/ng.1049
Publication dates
Published22 Jan 2012

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