• Article

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. https://doi.org/10.1038/ng.1049

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)https://doi.org/10.1038/ng.1049
Publication dates
Published22 Jan 2012

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Velentzis, L.S., Keshtgar, M.R., Woodside, J., Leathem, A., Titcomb, A., Perkins, A., Mazurowska, M., Anderson, V., Wardell, K. and Cantwell, M.M. 2011. Significant changes in dietary intake and supplement use after breast cancer diagnosis in a UK multicentre study. Breast Cancer Research and Treatment. 128 (2), pp. 473-482. https://doi.org/10.1007/s10549-010-1238-8

Abstract B76 - An overview of the DietCompLyf study - a multicentre UK study to evaluate the role of diet, lifestyle and complementary medicine use on breast cancer recurrence
Swann, R., Perkins, A., Dahya, P., Woodside, J., Dutton, S., Robertson, C.E., Velentzis, L.S., Leathem, A. and Dwek, M. 2011. Abstract B76 - An overview of the DietCompLyf study - a multicentre UK study to evaluate the role of diet, lifestyle and complementary medicine use on breast cancer recurrence. National Cancer Research Institute (NCRI) Cancer Conference 2011. BT Convention Centre, Liverpool, UK 06 - 09 Nov 2011

Lectin microarray profiling of metastatic breast cancers
Fry, S., Afrough, B., Lomax-Browne, H., Timms, J.F., Velentzis, L.S. and Leathem, A. 2011. Lectin microarray profiling of metastatic breast cancers. Glycobiology. 21 (8), pp. 1060-1070. https://doi.org/10.1093/glycob/cwr045

Abstract LB14 - Lectin microarray profilling of metastatic breast cancers
Fry, S., Afrough, B., Lomax-Browne, H., Timms, J.F., Velentzis, L.S. and Dwek, M. 2011. Abstract LB14 - Lectin microarray profilling of metastatic breast cancers. National Cancer Research Institute (NCRI) Cancer Conference 2011. BT Convention Centre, Liverpool, UK 06 - 09 Nov 2011

Vascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 are localised primarily to vasculature in human primary solid cancers
Smith, N.R., Baker, D., James, N.H., Ratcliffe, K., Jenkins, M., Ashton, S.E., Sproat, G., Swann, R., Gray, N., Ryan, A., Jürgensmeier, J.M. and Womack, C. 2010. Vascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 are localised primarily to vasculature in human primary solid cancers. Clinical Cancer Research. 16 (14), pp. 3548-3561. https://doi.org/10.1158/1078-0432

Permalink - https://westminsterresearch.westminster.ac.uk/item/8z564/genome-wide-association-analysis-identifies-three-new-breast-cancer-susceptibility-loci


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