The EPIC-Norfolk Study
Association of ESR1 gene tagging SNPs with breast cancer risk.
Human Molecular Genetics 2009 ; 18: 1131-9.
Dunning AM, Healey CS, Baynes C, Maia AT, Scollen S, Vega A, Rodríguez R, Barbosa-Morais NL, Ponder BA, SEARCH SEARCH, Low YL, Bingham S, EPIC EPIC, Haiman CA, Le Marchand L, MEC MEC, Broeks A, Schmidt MK, ABCS ABCS, Hopper J, Southey M, ABCFS ABCFS, Beckmann MW, Fasching PA, BBCC BBCC, Peto J, Johnson N, BBCS BBCS, Bojesen SE, Nordestgaard B, CGPS CGPS, Milne RL, Benitez J, CNIO-BCS CNIO-BCS, Hamann U, Ko Y, GENICA GENICA, Schmutzler RK, Burwinkel B, GC-HBOC GC-HBOC, Schürmann P, Dörk T, HABCS HABCS, Heikkinen T, Nevanlinna H, HEBCS HEBCS, Lindblom A, Margolin S, KARBAC KARBAC, Mannermaa A, Kosma VM, KBCS KBCS, Chen X, Spurdle A, kConFab and the AOCS Management Group, Change-Claude J, Flesch-Janys D, MARIE MARIE, Couch FJ, Olson JE, for MCBCS for MCBCS, Severi G, Baglietto L, MCCS MCCS, Børresen-Dale AL, Kristensen V, NBCS NBCS, Hunter DJ, Hankinson SE, NHS NHS, Devilee P, Vreeswijk M, ORIGO ORIGO, Lissowska J, Brinton L, PBCS PBCS, Liu J, Hall P, SASBAC SASBAC, Kang D, Yoo KY, SEBCS SEBCS, Shen CY, Yu JC, TWBCS TWBCS, Anton-Culver H, Ziogoas A, UCIBCS UCIBCS, Sigurdson A, Struewing J, USRTS USRTS, Easton DF, García-Closas M, Humphreys MK, Morrison J, Pharoah PD, Pooley KA, Chenevix-Trench G, and BCAC BCAC
DOI : 10.1093/hmg/ddn429
PubMed ID : 19126777
PMCID : PMC2722230
URL : https://academic.oup.com/hmg/article/18/6/1131/611801
Abstract
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.