Dunning AM, Healey CS, Baynes C, Maia AT, Scollen S, Vega A, Rodriguez R, Barbosa-Morais NL, Ponder BA, Low YL, Bingham S, Haiman CA, Le Marchand L, Broeks A, Schmidt MK, Hopper J, Southey M, Beckmann MW, Fasching PA, Peto J, Johnson N, Bojesen SE, Nordestgaard B, Milne RL, Benitez J, Hamann U, Ko Y, Schmutzler RK, Burwinkel B, Schurmann P, Dork T, Heikkinen T, Nevanlinna H, Lindblom A, Margolin S, Mannermaa A, Kosma VM, Chen X, Spurdle A, Change-Claude J, Flesch-Janys D, Couch FJ, Olson JE, Severi G, Baglietto L, Borresen-Dale AL, Kristensen V, Hunter DJ, Hankinson SE, Devilee P, Vreeswijk M, Lissowska J, Brinton L, Liu J, Hall P, Kang D, Yoo KY, Shen CY, Yu JC, Anton-Culver H, Ziogoas A, Sigurdson A, Struewing J, Easton DF, Garcia-Closas M, Humphreys MK, Morrison J, Pharoah PD, Pooley KA, Chenevix-Trench G (2009) Association of ESR1 gene tagging SNPs with breast cancer risk. Hum Mol Genet 18:1131-1139
We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55,000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations. Carriers of the c-allele have an odds ratio (OR) of 1.05 [95% Confidence Intervals (CI) 1.02-1.09] relative to t-allele homozygotes, P = 0.004. There is significant heterogeneity between studies, P = 0.002. The increased risk appears largely confined to oestrogen receptor-positive tumour risk. The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms.