Genome-wide association studies identify four ER negative-specific breast cancer risk loci

Montserrat Garcia-Closas, Fergus J. Couch, Sara Lindstrom, Kyriaki Michailidou, Marjanka K Schmidt, Mark N Brook, Nick Orr, Suhn Kyong Rhie, Elio Riboli, Heather Spencer Feigelson, Loic Le Marchand, Julie E Buring, Diana M. Eccles, Penelope Miron, Peter A Fasching, Hiltrud Brauch, Jenny Chang-Claude, Jane Carpenter, Andrew K Godwin, Heli NevanlinnaGraham G Giles, Angela Cox, John L Hopper, Manjeet K Bolla, Qin Wang, Joe Dennis, Ed Dicks, Will J Howat, Nils Schoof, Stig E Bojesen, Diether Lambrechts, Annegien Broeks, Irene L Andrulis, Pascal Guénel, Barbara Burwinkel, Elinor J Sawyer, Antoinette Hollestelle, Olivia Fletcher, Robert Winqvist, Hermann Brenner, Arto Mannermaa, Ute Hamann, Alfons Meindl, Annika Lindblom, Wei Zheng, Peter Devillee, Mark S. Goldberg, Jan Lubinski, Vessela Kristensen, Anthony J Swerdlow, Gene ENvironmental Interaction and breast CAncer (GENICA) Network

Research output: Contribution to journalArticle

274 Citations (Scopus)

Abstract

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

Original languageEnglish
Pages (from-to)392-8, 398e1-2
JournalNature Genetics
Volume45
Issue number4
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Breast Neoplasms
  • Case-Control Studies
  • Cooperative Behavior
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Meta-Analysis as Topic
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Receptors, Estrogen
  • Risk Factors
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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    Garcia-Closas, M., Couch, F. J., Lindstrom, S., Michailidou, K., Schmidt, M. K., Brook, M. N., Orr, N., Rhie, S. K., Riboli, E., Feigelson, H. S., Le Marchand, L., Buring, J. E., Eccles, D. M., Miron, P., Fasching, P. A., Brauch, H., Chang-Claude, J., Carpenter, J., Godwin, A. K., ... Gene ENvironmental Interaction and breast CAncer (GENICA) Network (2013). Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nature Genetics, 45(4), 392-8, 398e1-2. https://doi.org/10.1038/ng.2561