A genome-wide association study identifies suscept... [Nat Genet. 2010] - PubMed result

Nat Genet. 2010 Sep 19. [Epub ahead of print]

A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24.
Goode EL, Chenevix-Trench G, Song H, Ramus SJ, Notaridou M, Lawrenson K, Widschwendter M, Vierkant RA, Larson MC, Kjaer SK, Birrer MJ, Berchuck A, Schildkraut J, Tomlinson I, Kiemeney LA, Cook LS, Gronwald J, Garcia-Closas M, Gore ME, Campbell I, Whittemore AS, Sutphen R, Phelan C, Anton-Culver H, Pearce CL, Lambrechts D, Rossing MA, Chang-Claude J, Moysich KB, Goodman MT, Dörk T, Nevanlinna H, Ness RB, Rafnar T, Hogdall C, Hogdall E, Fridley BL, Cunningham JM, Sieh W, McGuire V, Godwin AK, Cramer DW, Hernandez D, Levine D, Lu K, Iversen ES, Palmieri RT, Houlston R, van Altena AM, Aben KK, Massuger LF, Brooks-Wilson A, Kelemen LE, Le ND, Jakubowska A, Lubinski J, Medrek K, Stafford A, Easton DF, Tyrer J, Bolton KL, Harrington P, Eccles D, Chen A, Molina AN, Davila BN, Arango H, Tsai YY, Chen Z, Risch HA, McLaughlin J, Narod SA, Ziogas A, Brewster W, Gentry-Maharaj A, Menon U, Wu AH, Stram DO, Pike MC; The Wellcome Trust Case-Control Consortium, Beesley J, Webb PM; The Australian Cancer Study (Ovarian Cancer); The Australian Ovarian Cancer Study Group; the Ovarian Cancer Association Consortium (OCAC), Chen X, Ekici AB, Thiel FC, Beckmann MW, Yang H, Wentzensen N, Lissowska J, Fasching PA, Despierre E, Amant F, Vergote I, Doherty J, Hein R, Wang-Gohrke S, Lurie G, Carney ME, Thompson PJ, Runnebaum I, Hillemanns P, Dürst M, Antonenkova N, Bogdanova N, Leminen A, Butzow R, Heikkinen T, Stefansson K, Sulem P, Besenbacher S, Sellers TA, Gayther SA, Pharoah PD.

[1] Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. [2] These authors contributed equally to this work.

Abstract
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.

PMID: 20852632 [PubMed - as supplied by publisher]
A genome-wide association study identifies suscept... [Nat Genet. 2010] - PubMed result