TY - JOUR
T1 - Association analysis identifies 65 new breast cancer risk loci
AU - NBCS Collaborators
AU - ABCTB Investigators
AU - kConFab/AOCS Investigators
AU - Michailidou, Kyriaki
AU - Lindström, Sara
AU - Dennis, Joe
AU - Beesley, Jonathan
AU - Hui, Shirley
AU - Kar, Siddhartha
AU - Lemaçon, Audrey
AU - Soucy, Penny
AU - Glubb, Dylan
AU - Rostamianfar, Asha
AU - Bolla, Manjeet K.
AU - Wang, Qin
AU - Tyrer, Jonathan
AU - Dicks, Ed
AU - Lee, Andrew
AU - Wang, Zhaoming
AU - Allen, Jamie
AU - Keeman, Renske
AU - Eilber, Ursula
AU - French, Juliet D.
AU - Chen, Xiao Qing
AU - Fachal, Laura
AU - McCue, Karen
AU - Reed, Amy E.Mc Cart
AU - Ghoussaini, Maya
AU - Carroll, Jason S.
AU - Jiang, Xia
AU - Finucane, Hilary
AU - Adams, Marcia
AU - Adank, Muriel A.
AU - Ahsan, Habibul
AU - Aittomäki, Kristiina
AU - Anton-Culver, Hoda
AU - Antonenkova, Natalia N.
AU - Arndt, Volker
AU - Aronson, Kristan J.
AU - Arun, Banu
AU - Auer, Paul L.
AU - Bacot, François
AU - Barrdahl, Myrto
AU - Baynes, Caroline
AU - Beckmann, Matthias W.
AU - Behrens, Sabine
AU - Benitez, Javier
AU - Bermisheva, Marina
AU - Bernstein, Leslie
AU - Blomqvist, Carl
AU - Bogdanova, Natalia V.
AU - Bojesen, Stig E.
AU - Torres, Diana
N1 - Publisher Copyright:
© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2017/11/2
Y1 - 2017/11/2
N2 - Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
AB - Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
UR - https://www.scopus.com/pages/publications/85033379332
U2 - 10.1038/nature24284
DO - 10.1038/nature24284
M3 - Article
C2 - 29059683
AN - SCOPUS:85033379332
SN - 0028-0836
VL - 551
SP - 92
EP - 94
JO - Nature
JF - Nature
IS - 7678
ER -
ODS 3: Salud y bienestar