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Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31.

Publication ,  Journal Article
Permuth-Wey, J; Lawrenson, K; Shen, HC; Velkova, A; Tyrer, JP; Chen, Z; Lin, H-Y; Chen, YA; Tsai, Y-Y; Qu, X; Ramus, SJ; Karevan, R; Lee, J ...
Published in: Nat Commun
2013

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

2013

Volume

4

Start / End Page

1627

Location

England

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Humans
  • Genetic Predisposition to Disease
  • Female
  • Chromosomes, Human, Pair 17
  • Carcinoma, Ovarian Epithelial
 

Citation

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Chicago
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MLA
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Permuth-Wey, J., Lawrenson, K., Shen, H. C., Velkova, A., Tyrer, J. P., Chen, Z., … Gayther, S. A. (2013). Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31. Nat Commun, 4, 1627. https://doi.org/10.1038/ncomms2613
Permuth-Wey, Jennifer, Kate Lawrenson, Howard C. Shen, Aneliya Velkova, Jonathan P. Tyrer, Zhihua Chen, Hui-Yi Lin, et al. “Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31.Nat Commun 4 (2013): 1627. https://doi.org/10.1038/ncomms2613.
Permuth-Wey J, Lawrenson K, Shen HC, Velkova A, Tyrer JP, Chen Z, et al. Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31. Nat Commun. 2013;4:1627.
Permuth-Wey, Jennifer, et al. “Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31.Nat Commun, vol. 4, 2013, p. 1627. Pubmed, doi:10.1038/ncomms2613.
Permuth-Wey J, Lawrenson K, Shen HC, Velkova A, Tyrer JP, Chen Z, Lin H-Y, Chen YA, Tsai Y-Y, Qu X, Ramus SJ, Karevan R, Lee J, Lee N, Larson MC, Aben KK, Anton-Culver H, Antonenkova N, Antoniou AC, Armasu SM, Australian Cancer Study, Australian Ovarian Cancer Study, Bacot F, Baglietto L, Bandera EV, Barnholtz-Sloan J, Beckmann MW, Birrer MJ, Bloom G, Bogdanova N, Brinton LA, Brooks-Wilson A, Brown R, Butzow R, Cai Q, Campbell I, Chang-Claude J, Chanock S, Chenevix-Trench G, Cheng JQ, Cicek MS, Coetzee GA, Consortium of Investigators of Modifiers of BRCA1/2, Cook LS, Couch FJ, Cramer DW, Cunningham JM, Dansonka-Mieszkowska A, Despierre E, Doherty JA, Dörk T, du Bois A, Dürst M, Easton DF, Eccles D, Edwards R, Ekici AB, Fasching PA, Fenstermacher DA, Flanagan JM, Garcia-Closas M, Gentry-Maharaj A, Giles GG, Glasspool RM, Gonzalez-Bosquet J, Goodman MT, Gore M, Górski B, Gronwald J, Hall P, Halle MK, Harter P, Heitz F, Hillemanns P, Hoatlin M, Høgdall CK, Høgdall E, Hosono S, Jakubowska A, Jensen A, Jim H, Kalli KR, Karlan BY, Kaye SB, Kelemen LE, Kiemeney LA, Kikkawa F, Konecny GE, Krakstad C, Kjaer SK, Kupryjanczyk J, Lambrechts D, Lambrechts S, Lancaster JM, Le ND, Leminen A, Levine DA, Liang D, Lim BK, Lin J, Lissowska J, Lu KH, Lubiński J, Lurie G, Massuger LFAG, Matsuo K, McGuire V, McLaughlin JR, Menon U, Modugno F, Moysich KB, Nakanishi T, Narod SA, Nedergaard L, Ness RB, Nevanlinna H, Nickels S, Noushmehr H, Odunsi K, Olson SH, Orlow I, Paul J, Pearce CL, Pejovic T, Pelttari LM, Pike MC, Poole EM, Raska P, Renner SP, Risch HA, Rodriguez-Rodriguez L, Rossing MA, Rudolph A, Runnebaum IB, Rzepecka IK, Salvesen HB, Schwaab I, Severi G, Shridhar V, Shu X-O, Shvetsov YB, Sieh W, Song H, Southey MC, Spiewankiewicz B, Stram D, Sutphen R, Teo S-H, Terry KL, Tessier DC, Thompson PJ, Tworoger SS, van Altena AM, Vergote I, Vierkant RA, Vincent D, Vitonis AF, Wang-Gohrke S, Palmieri Weber R, Wentzensen N, Whittemore AS, Wik E, Wilkens LR, Winterhoff B, Woo YL, Wu AH, Xiang Y-B, Yang HP, Zheng W, Ziogas A, Zulkifli F, Phelan CM, Iversen E, Schildkraut JM, Berchuck A, Fridley BL, Goode EL, Pharoah PDP, Monteiro ANA, Sellers TA, Gayther SA. Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31. Nat Commun. 2013;4:1627.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

2013

Volume

4

Start / End Page

1627

Location

England

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Humans
  • Genetic Predisposition to Disease
  • Female
  • Chromosomes, Human, Pair 17
  • Carcinoma, Ovarian Epithelial