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Association of ESR1 gene tagging SNPs with breast cancer risk

2009; Oxford University Press; Volume: 18; Issue: 6 Linguagem: Inglês

10.1093/hmg/ddn429

1460-2083

Alison M. Dunning, Catherine S. Healey, Caroline Baynes, Ana-Teresa Maia, Serena Scollen, Ana Vega, Raquel Rodríguez, Nuno L. Barbosa‐Morais, Bruce A.J. Ponder, Yen-Ling Low, Sheila Bingham, Christopher A. Haiman, Loı̈c Le Marchand, Annegien Broeks, Marjanka K. Schmidt, John L. Hopper, Melissa C. Southey, Matthias W. Beckmann, Peter A. Fasching, Julian Peto, Nichola Johnson, Stig E. Bojesen, Børge G. Nordestgaard, Roger L. Milne, Javier Benı́tez, Ute Hamann, Yon Ko, Rita K. Schmutzler, Barbara Burwinkel, Peter Schürmann, Thilo Dörk, Tuomas Heikkinen, Heli Nevanlinna, Annika Lindblom, Sara Margolin, Graham J. Mann, Veli-Matti Kosma, Xiaohong Chen, Amanda B. Spurdle, Jenny Change-Claude, Dieter Flesch‐Janys, Fergus J. Couch, Janet E. Olson, Gianluca Severi, Laura Baglietto, Anne‐Lise Børresen‐Dale, Vessela Kristensen, David J. Hunter, Susan E. Hankinson, Peter Devilee, Maaike P.G. Vreeswijk, Jolanta Lissowska, Louise A. Brinton, Jianjun Liu, Per Hall, Daehee Kang, Keun-Young Yoo, Chen‐Yang Shen, Jyh-Cherng Yu, Hoda Anton‐Culver, Argyrios Ziogoas, Alice J. Sigurdson, Jeffery P. Struewing, Douglas F. Easton, Montserrat García‐Closas, Manjeet K. Humphreys, Jonathan J. Morrison, Paul D.P. Pharoah, Karen A. Pooley, Georgia Chenevix‐Trench,

Nutrition, Genetics, and Disease

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.