Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2.
Ahmed S., Thomas G., Ghoussaini M., Healey CS., Humphreys MK., Platte R., Morrison J., Maranian M., Pooley KA., Luben R., Eccles D., Evans DG., Fletcher O., Johnson N., dos Santos Silva I., Peto J., Stratton MR., Rahman N., Jacobs K., Prentice R., Anderson GL., Rajkovic A., Curb JD., Ziegler RG., Berg CD., Buys SS., McCarty CA., Feigelson HS., Calle EE., Thun MJ., Diver WR., Bojesen S., Nordestgaard BG., Flyger H., Dörk T., Schürmann P., Hillemanns P., Karstens JH., Bogdanova NV., Antonenkova NN., Zalutsky IV., Bermisheva M., Fedorova S., Khusnutdinova E., SEARCH None., Kang D., Yoo K-Y., Noh DY., Ahn S-H., Devilee P., van Asperen CJ., Tollenaar RAEM., Seynaeve C., Garcia-Closas M., Lissowska J., Brinton L., Peplonska B., Nevanlinna H., Heikkinen T., Aittomäki K., Blomqvist C., Hopper JL., Southey MC., Smith L., Spurdle AB., Schmidt MK., Broeks A., van Hien RR., Cornelissen S., Milne RL., Ribas G., González-Neira A., Benitez J., Schmutzler RK., Burwinkel B., Bartram CR., Meindl A., Brauch H., Justenhoven C., Hamann U., GENICA Consortium None., Chang-Claude J., Hein R., Wang-Gohrke S., Lindblom A., Margolin S., Mannermaa A., Kosma V-M., Kataja V., Olson JE., Wang X., Fredericksen Z., Giles GG., Severi G., Baglietto L., English DR., Hankinson SE., Cox DG., Kraft P., Vatten LJ., Hveem K., Kumle M., Sigurdson A., Doody M., Bhatti P., Alexander BH., Hooning MJ., van den Ouweland AMW., Oldenburg RA., Schutte M., Hall P., Czene K., Liu J., Li Y., Cox A., Elliott G., Brock I., Reed MWR., Shen C-Y., Yu J-C., Hsu G-C., Chen S-T., Anton-Culver H., Ziogas A., Andrulis IL., Knight JA., kConFab None., Australian Ovarian Cancer Study Group None., Beesley J., Goode EL., Couch F., Chenevix-Trench G., Hoover RN., Ponder BAJ., Hunter DJ., Pharoah PDP., Dunning AM., Chanock SJ., Easton DF.
Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08-1.13, P = 4.1 x 10(-23)) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92-0.97, P = 1.4 x 10(-8)). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.