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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Antonis C Antoniou
  • Xianshu Wang
  • Zachary S Fredericksen
  • Lesley McGuffog
  • Robert Tarrell
  • Olga M Sinilnikova
  • Sue Healey
  • Jonathan Morrison
  • Christiana Kartsonaki
  • Timothy Lesnick
  • Maya Ghoussaini
  • Daniel Barrowdale
  • Susan Peock
  • Margaret Cook
  • Clare Oliver
  • Debra Frost
  • Diana Eccles
  • D Gareth Evans
  • Ros Eeles
  • Louise Izatt
  • Carol Chu
  • Fiona Douglas
  • Joan Paterson
  • Dominique Stoppa-Lyonnet
  • Claude Houdayer
  • Sylvie Mazoyer
  • Sophie Giraud
  • Christine Lasset
  • Audrey Remenieras
  • Olivier Caron
  • Agnès Hardouin
  • Pascaline Berthet
  • Frans B L Hogervorst
  • Matti A Rookus
  • Agnes Jager
  • Ans van den Ouweland
  • Nicoline Hoogerbrugge
  • Rob B van der Luijt
  • Hanne Meijers-Heijboer
  • Encarna B Gómez García
  • Peter Devilee
  • Maaike P G Vreeswijk
  • Jan Lubinski
  • Anna Jakubowska
  • Jacek Gronwald
  • Tomasz Huzarski
  • Tomasz Byrski
  • Gerdes, Anne-Marie Axø
  • Thomas V O Hansen
  • Nielsen, Finn Cilius
  • EMBRACE
Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P(trend) = 2.3 × 10¿¿ to P(trend) = 3.9 × 10¿7), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P(trend) = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P(trend) = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (P(trend) = 1 × 10¿7) to P(trend) = 8 × 10¿5; rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P(trend) = 1.1 × 10¿7
OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind42
Udgave nummer10
Sider (fra-til)885-92
Antal sider8
ISSN1061-4036
DOI
StatusUdgivet - 1 okt. 2010

ID: 34104649