Genome-wide association study identifies novel breast cancer susceptibility loci

Reference details

Easton DFP, K. A.; Dunning, A. M.; Pharoah, P. D.; Thompson, D.; Ballinger, D. G.; Struewing, J. P.; Morrison, J.; Field, H.; Luben, R.; Wareham, N.; Ahmed, S.; Healey, C. S.; Bowman, R.; Meyer, K. B.; Haiman, C. A.; Kolonel, L. K.; Henderson, B. E.; Le Marchand, L.; Brennan, P.; Sangrajrang, S.; Gaborieau, V.; Odefrey, F.; Shen, C. Y.; Wu, P. E.; Wang, H. C.; Eccles, D.; Evans, D. G.; Peto, J.; Fletcher, O.; Johnson, N.; Seal, S.; Stratton, M. R.; Rahman, N.; Chenevix-Trench, G.; Bojesen, S. E.; Nordestgaard, B. G.; Axelsson, C. K.; Garcia-Closas, M.; Brinton, L.; Chanock, S.; Lissowska, J.; Peplonska, B.; Nevanlinna, H.; Fagerholm, R.; Eerola, H.; Kang, D.; Yoo, K. Y.; Noh, D. Y.; Ahn, S. H.; Hunter, D. J.; Hankinson, S. E.; Cox, D. G.; Hall, P.; Wedren, S.; Liu, J.; Low, Y. L.; Bogdanova, N.; Schurmann, P.; Dork, T.; Tollenaar, R. A.; Jacobi, C. E.; Devilee, P.; Klijn, J. G.; Sigurdson, A. J.; Doody, M. M.; Alexander, B. H.; Zhang, J.; Cox, A.; Brock, I. W.; MacPherson, G.; Reed, M. W.; Couch, F. J.; Goode, E. L.; Olson, J. E.; Meijers-Heijboer, H.; van den Ouweland, A.; Uitterlinden, A.; Rivadeneira, F.; Milne, R. L.; Ribas, G.; Gonzalez-Neira, A.; Benitez, J.; Hopper, J. L.; McCredie, M.; Southey, M.; Giles, G. G.; Schroen, C.; Justenhoven, C.; Brauch, H.; Hamann, U.; Ko, Y. D.; Spurdle, A. B.; Beesley, J.; Chen, X.; Mannermaa, A.; Kosma, V. M.; Kataja, V.; Hartikainen, J.; Day, N. E.; Cox, D. R.; Ponder, B. A. (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447:1087-1093


Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10(-7)).="" four="" of="" these="" contain="" plausible="" causative="" genes="" (fgfr2,="" tnrc9,="" map3k1="" and="" lsp1).="" at="" the="" second="" stage,="" 1,792="" snps="" were="" significant="" at="" the="" p="">< 0.05="" level="" compared="" with="" an="" estimated="" 1,343="" that="" would="" be="" expected="" by="" chance,="" indicating="" that="" many="" additional="" common="" susceptibility="" alleles="" may="" be="" identifiable="" by="" this="">

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