학술논문
Association of ESR1 gene tagging SNPs with breast cancer risk
Document Type
article
Author
Dunning, Alison M; Healey, Catherine S; Baynes, Caroline; Maia, Ana-Teresa; Scollen, Serena; Vega, Ana; Rodríguez, Raquel; Barbosa-Morais, Nuno L; Ponder, Bruce AJ; Low, Yen-Ling; Bingham, Sheila; Haiman, Christopher A; Le Marchand, Loic; Broeks, Annegien; Schmidt, Marjanka K; Hopper, John; Southey, Melissa; Beckmann, Matthias W; Fasching, Peter A; Peto, Julian; Johnson, Nichola; Bojesen, Stig E; Nordestgaard, Børge; Milne, Roger L; Benitez, Javier; Hamann, Ute; Ko, Yon; Schmutzler, Rita K; Burwinkel, Barbara; Schürmann, Peter; Dörk, Thilo; Heikkinen, Tuomas; Nevanlinna, Heli; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Chen, Xiaoqing; Spurdle, Amanda; Change-Claude, Jenny; Flesch-Janys, Dieter; Couch, Fergus J; Olson, Janet E; Severi, Gianluca; Baglietto, Laura; Børresen-Dale, Anne-Lise; Kristensen, Vessela; Hunter, David J; Hankinson, Susan E; Devilee, Peter; Vreeswijk, Maaike; Lissowska, Jolanta; Brinton, Louise; Liu, Jianjun; Hall, Per; Kang, Daehee; Yoo, Keun-Young; Shen, Chen-Yang; Yu, Jyh-Cherng; Anton-Culver, Hoda; Ziogoas, Argyrios; Sigurdson, Alice; Struewing, Jeff; Easton, Douglas F; Garcia-Closas, Montserrat; Humphreys, Manjeet K; Morrison, Jonathan; Pharoah, Paul DP; Pooley, Karen A; Chenevix-Trench, Georgia
Source
Human Molecular Genetics. 18(6)
Subject
Language
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.