Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

Antoniou, A.C. et al. (2011) Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers. Human Molecular Genetics, 20(16), pp. 3304-3321. (doi:10.1093/hmg/ddr226)

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Abstract

Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r<sup>2</sup> = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11–1.23, P-trend = 4.5 × 10<sup>−9</sup> for rs2046210; HR = 1.28, 95% CI: 1.18–1.40, P-trend = 1.3 × 10<sup>−8</sup> for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01–1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02–1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92–1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.

Item Type:Articles
Additional Information:Glasgow Author Edward Tobias part of the EMBRACE group.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tobias, Professor Edward
Authors: Antoniou, A.C., Kartsonaki, C., Sinilnikova, O.M., Soucy, P., McGuffog, L., Healey, S., Lee, A., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Cattaneo, E., Barile, M., Pensotti, V., Pasini, B., Dolcetti, R., Giannini, G., Laura Putignano, A., Varesco, L., Radice, P., Mai, P.L., Greene, M.H., Andrulis, I.L., Glendon, G., Ozcelik, H., Thomassen, M., Gerdes, A.-M., Kruse, T.A., Birk Jensen, U., Cruger, D.G., Caligo, M.A., Laitman, Y., Milgrom, R., Kaufman, B., Paluch-Shimon, S., Friedman, E., Loman, N., Harbst, K., Lindblom, A., Arver, B., Ehrencrona, H., Melin, B., Nathanson, K. L., Domchek, S.M., Rebbeck, T., Jakubowska, A., Lubinski, J., Gronwald, J., Huzarski, T., Byrski, T., Cybulski, C., Gorski, B., Osorio, A., Ramon y Cajal, T., Fostira, F., Andres, R., Benitez, J., Hamann, U., Hogervorst, F.B., Rookus, M.A., Hooning, M.J., Nelen, M.R., van der Luijt, R.B., van Os, T.A.M., van Asperen, C.J., Devilee, P., Meijers-Heijboer, H.E.J., Gomez Garcia, E.B., Peock, S., Cook, M., Frost, D., Platte, R., Leyland, J., Gareth Evans, D., Lalloo, F., Eeles, R., Izatt, L., Adlard, J., Davidson, R., Eccles, D., Ong, K.-R., Cook, J., Douglas, F., Paterson, J., John Kennedy, M., Miedzybrodzka, Z., Godwin, A., Stoppa-Lyonnet, D., Buecher, B., Belotti, M., Tirapo, C., Mazoyer, S., Barjhoux, L., Lasset, C., Leroux, D., Faivre, L., Bronner, M., Prieur, F., Nogues, C., Rouleau, E., Pujol, P., Coupier, I., Frenay, M., Hopper, J.L., Daly, M.B., Terry, M.B., John, E.M., Buys, S.S., Yassin, Y., Miron, A., Goldgar, D., Singer, C.F., Tea, M.-K., Pfeiler, G., Catharina Dressler, A., Hansen, T.v.O., Jonson, L., Ejlertsen, B., Bjork Barkardottir, R., Kirchhoff, T., Offit, K., Piedmonte, M., Rodriguez, G., Small, L., Boggess, J., Blank, S., Basil, J., Azodi, M., Ewart Toland, A., Montagna, M., Tognazzo, S., Agata, S., Imyanitov, E., Janavicius, R., Lazaro, C., Blanco, I., Pharoah, P.D.P., Sucheston, L., Karlan, B.Y., Walsh, C.S., Olah, E., Bozsik, A., Teo, S.-H., Seldon, J.L., Beattie, M. S., van Rensburg, E., Sluiter, M.D., Diez, O., Schmutzler, R.K., Wappenschmidt, B., Engel, C., Meindl, A., Ruehl, I., Varon-Mateeva, R., Kast, K., Deissler, H., Niederacher, D., Arnold, N., Gadzicki, D., Schonbuchner, I., Caldes, T., de la Hoya, M., Nevanlinna, H., Aittomaki, K., Dumont, M., Chiquette, J., Tischkowitz, M., Chen, X., Beesley, J., Spurdle, A. B., Neuhausen, S., Chun Ding, Y., Fredericksen, Z., Wang, X., Pankratz, V.S., Couch, F., Simard, J., Easton, D.F., Chenevix-Trench, G., and Tobias, E.S.
Subjects:Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
Journal Name:Human Molecular Genetics
ISSN:0964-6906
Published Online:18 May 2011

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