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Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the ovarian cancer association consortium

Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the ovarian cancer association consortium
Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the ovarian cancer association consortium
Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (P(heterogeneity)?0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR?=?0.6 to 0.9; P(trend)?=?0.001 to 0.03). Results from replication set 2 were statistically homogeneous (P(heterogeneity)?0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs?=?1.2; P(trend)?0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (P(heterogeneity)?0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (P(interaction)?0.003), age at diagnosis (P(interaction)?=?0.04), and year of diagnosis (P(interaction)?=?0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required.
1932-6203
e19642-[10pp]
Minna, John D.
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Minna, John D., Amankwah, Ernest K. and Wang, Qinggang et al. (2011) Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the ovarian cancer association consortium. PLoS ONE, 6 (5), e19642-[10pp]. (doi:10.1371/journal.pone.0019642). (PMID:21637745)

Record type: Article

Abstract

Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (P(heterogeneity)?0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR?=?0.6 to 0.9; P(trend)?=?0.001 to 0.03). Results from replication set 2 were statistically homogeneous (P(heterogeneity)?0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs?=?1.2; P(trend)?0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (P(heterogeneity)?0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (P(interaction)?0.003), age at diagnosis (P(interaction)?=?0.04), and year of diagnosis (P(interaction)?=?0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required.

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Accepted/In Press date: 12 April 2011
Published date: 27 May 2011
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 352340
URI: http://eprints.soton.ac.uk/id/eprint/352340
DOI: doi:10.1371/journal.pone.0019642
ISSN: 1932-6203
PURE UUID: a5e35fcc-7655-4d14-aab1-526b703a0f7b
ORCID for Diana M. Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 13 May 2013 10:23
Last modified: 15 Mar 2024 02:40

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Contributors

Author: John D. Minna
Author: Ernest K. Amankwah
Author: Qinggang Wang
Author: Joellen M. Schildkraut
Author: Ya-Yu Tsai
Author: Susan J. Ramus
Author: Brooke L. Fridley
Author: Jonathan Beesley
Author: Sharon E. Johnatty
Author: Penelope M. Webb
Author: Georgia Chenevix-Trench
Author: Laura C. Dale
Author: Diether Lambrechts
Author: Frederic Amant
Author: Evelyn Despierre
Author: Ignace Vergote
Author: Simon A. Gayther
Author: Aleksandra Gentry-Maharaj
Author: Usha Menon
Author: Jenny Chang-Claude
Author: Shan Wang-Gohrke
Author: Hoda Anton-Culver
Author: Argyrios Ziogas
Author: Thilo Dörk
Author: Matthias Dürst
Author: Natalia Antonenkova
Author: Natalia Bogdanova
Author: Robert Brown
Author: James M. Flanagan
Author: Stanley B. Kaye
Author: James Paul
Author: Ralf Bützow
Author: Heli Nevanlinna
Author: Ian Campbell
Author: Diana M. Eccles ORCID iD
Author: Beth Y. Karlan
Author: Jenny Gross
Author: Christine Walsh
Author: Paul D. P. Pharoah
Author: Honglin Song
Author: Susanne Krüger Kjær
Author: Estrid Høgdall
Author: Claus Høgdall
Author: Lene Lundvall
Author: Lotte Nedergaard
Author: Lambertus A. L. M. Kiemeney
Author: Leon F. A. G. Massuger
Author: Anne M. van Altena
Author: Sita H. H. M. Vermeulen
Author: Nhu D. Le
Author: Angela Brooks-Wilson
Author: Linda S. Cook
Author: Catherine M. Phelan
Author: Julie M. Cunningham
Author: Celine M. Vachon
Author: Robert A. Vierkant
Author: Edwin S. Iversen
Author: Andrew Berchuck
Author: Ellen L. Goode
Author: Thomas A. Sellers
Author: Linda E. Kelemen

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