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Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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  • Jiajun Shi
  • Yanfeng Zhang
  • Wei Zheng
  • Kyriaki Michailidou
  • Maya Ghoussaini
  • Manjeet K Bolla
  • Qin Wang
  • Joe Dennis
  • Michael Lush
  • Roger L Milne
  • Xiao-Ou Shu
  • Jonathan Beesley
  • Siddhartha Kar
  • Irene L Andrulis
  • Hoda Anton-Culver
  • Volker Arndt
  • Matthias W Beckmann
  • Zhiguo Zhao
  • Xingyi Guo
  • Javier Benitez
  • Alicia Beeghly-Fadiel
  • William Blot
  • Natalia V Bogdanova
  • Stig E Bojesen
  • Hiltrud Brauch
  • Hermann Brenner
  • Louise Brinton
  • Annegien Broeks
  • Thomas Brüning
  • Barbara Burwinkel
  • Hui Cai
  • Sander Canisius
  • Jenny Chang-Claude
  • Ji-Yeob Choi
  • Fergus J Couch
  • Angela Cox
  • Simon S Cross
  • Kamila Czene
  • Hatef Darabi
  • Peter Devilee
  • Arnaud Droit
  • Thilo Dork
  • Peter A Fasching
  • Olivia Fletcher
  • Henrik Flyger
  • Florentia Fostira
  • Valerie Gaborieau
  • Montserrat García-Closas
  • Graham G Giles
  • Mervi Grip
  • kConFab Investigators
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Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.

OriginalsprogEngelsk
TidsskriftRadiation Oncology Investigations
Vol/bind139
Udgave nummer6
Sider (fra-til)1303-17
Antal sider15
ISSN0020-7136
DOI
StatusUdgivet - 15 sep. 2016

ID: 49443799