A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Ellen L Goode
  • Georgia Chenevix-Trench
  • Honglin Song
  • Susan J Ramus
  • Maria Notaridou
  • Kate Lawrenson
  • Martin Widschwendter
  • Robert A Vierkant
  • Melissa C Larson
  • Susanne K Kjaer
  • Michael J Birrer
  • Andrew Berchuck
  • Joellen Schildkraut
  • Ian Tomlinson
  • Lambertus A Kiemeney
  • Linda S Cook
  • Jacek Gronwald
  • Montserrat Garcia-Closas
  • Martin E Gore
  • Ian Campbell
  • Alice S Whittemore
  • Rebecca Sutphen
  • Catherine Phelan
  • Hoda Anton-Culver
  • Celeste Leigh Pearce
  • Diether Lambrechts
  • Mary Anne Rossing
  • Jenny Chang-Claude
  • Kirsten B Moysich
  • Marc T Goodman
  • Thilo Dörk
  • Heli Nevanlinna
  • Roberta B Ness
  • Thorunn Rafnar
  • Høgdall, Claus Kim
  • Estrid Hogdall
  • Brooke L Fridley
  • Julie M Cunningham
  • Weiva Sieh
  • Valerie McGuire
  • Andrew K Godwin
  • Daniel W Cramer
  • Dena Hernandez
  • Douglas Levine
  • Karen Lu
  • Edwin S Iversen
  • Rachel T Palmieri
  • Richard Houlston
  • Anne M van Altena
  • Katja K H Aben
  • Wellcome Trust Case-Control Consortium
Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P = 10¿4) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P = 5 × 10¿8 (8q24, P = 8.0 × 10¿¹5 and 2q31, P = 3.8 × 10¿¹4) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10¿8 and 17q21, P = 1.4 × 10¿7). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.
OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind42
Udgave nummer10
Sider (fra-til)874-9
Antal sider6
ISSN1061-4036
DOI
StatusUdgivet - 1 okt. 2010

ID: 34157980