Polymorphisms in Stromal Genes and Susceptibility to Serous Epithelial Ovarian Cancer: A Report from the Ovarian Cancer Association Consortium

Title: Polymorphisms in Stromal Genes and Susceptibility to Serous Epithelial Ovarian Cancer: A Report from the Ovarian Cancer Association Consortium
Authors: Amankwah, EK
Wang, Q
Schildkraut, JM
Tsai, Y-Y
Ramus, SJ
Fridley, BL
Beesley, J
Johnatty, SE
Webb, PM
Chenevix-Trench, G
Dale, LC
Lambrechts, D
Amant, F
Despierre, E
Vergote, I
Gayther, SA
Gentry-Maharaj, A
Menon, U
Chang-Claude, J
Wang-Gohrke, S
Anton-Culver, H
Ziogas, A
Doerk, T
Duerst, M
Antonenkova, N
Bogdanova, N
Brown, R
Flanagan, JM
Kaye, SB
Paul, J
Butzow, R
Nevanlinna, H
Campbell, I
Eccles, DM
Karlan, BY
Gross, J
Walsh, C
Pharoah, PDP
Song, H
Kjaer, SK
Hogdall, E
Hogdall, C
Lundvall, L
Nedergaard, L
Kiemeney, LALM
Massuger, LFAG
Van Altena, AM
Vermeulen, SHHM
Le, ND
Brooks-Wilson, A
Cook, LS
Phelan, CM
Cunningham, JM
Vachon, CM
Vierkant, RA
Iversen, ES
Berchuck, A
Goode, EL
Sellers, TA
Kelemen, LE
Item Type: Journal 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 (Pheterogeneity≥0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; Ptrend = 0.001 to 0.03). Results from replication set 2 were statistically homogeneous (Pheterogeneity≥0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs = 1.2; Ptrend≤0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (Pheterogeneity≤0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (Pinteraction≤0.003), age at diagnosis (Pinteraction = 0.04), and year of diagnosis (Pinteraction = 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.
Issue Date: 27-May-2011
Date of Acceptance: 12-Apr-2011
URI: http://hdl.handle.net/10044/1/40816
DOI: http://dx.doi.org/10.1371/journal.pone.0019642
ISSN: 1932-6203
Publisher: Public Library of Science
Journal / Book Title: PLOS One
Volume: 6
Issue: 5
Copyright Statement: © 2011 Amankwah et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Cancer Research UK
Funder's Grant Number: C536/A13086
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
GROWTH-FACTOR-BETA
GENOME-WIDE ASSOCIATION
MAMMARY-GLAND
TGF-BETA
ORAL-CONTRACEPTIVES
EXPRESSION
DECORIN
RISK
CARCINOMA
TRENDS
Alleles
Case-Control Studies
Confidence Intervals
Female
Genes, Neoplasm
Genetic Predisposition to Disease
Humans
Middle Aged
Neoplasms, Cystic, Mucinous, and Serous
Neoplasms, Glandular and Epithelial
Odds Ratio
Ovarian Neoplasms
Polymorphism, Single Nucleotide
Stromal Cells
Australian Ovarian Cancer Study Group
General Science & Technology
MD Multidisciplinary
Publication Status: Published
Article Number: e19642
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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