Amankwah, EK;
Wang, QG;
Schildkraut, JM;
Tsai, YY;
Ramus, SJ;
Fridley, BL;
Beesley, J;
... Australian Ovarian Canc Study Grp; + view all
(2011)
Polymorphisms in Stromal Genes and Susceptibility to Serous Epithelial Ovarian Cancer: A Report from the Ovarian Cancer Association Consortium.
PLOS ONE
, 6
(5)
, Article e19642. 10.1371/journal.pone.0019642.
![[thumbnail of 1309714.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/application_pdf.png) Preview |
PDF
1309714.pdf Download (309kB) |
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.
| Type: | Article |
|---|---|
| Title: | Polymorphisms in Stromal Genes and Susceptibility to Serous Epithelial Ovarian Cancer: A Report from the Ovarian Cancer Association Consortium |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0019642 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0019642 |
| Language: | English |
| Additional information: | © 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. Australia: National Health and Medical Research Council (199600), Cancer Council Tasmania, Cancer Foundation of Western Australia; Belgium: National Cancer Plan - Action 29; Canada: Alberta Heritage Foundation for Medical Research, Worksafe BC, Canadian Institutes of Health Research, Michael Smith Foundation for Health Research; Denmark: Mermaid 1, The Danish Cancer Society; Finland: Helsinki University Central Hospital Research Fund, Academy of Finland, the Finnish Cancer Society; Germany: European Community's Seventh Framework Programme (HEALTH-F2-2009-223175), Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (01 GB 9401), University of Ulm (P.685); Netherlands: Radboud University Nijmegen Medical Centre, the municipality and community health service of Nijmegen; U.K.: Cancer Research UK, Association for International Cancer Research, St Andrews, Lon V. Smith Foundation grant LVS-39420, Eve Appeal, OAK Foundation; National Institute for Health Research Biomedical Research Centre; U.S.: Ovarian Cancer Research Fund, National Institutes of Health (R01-CA-61107, R01-CA-122443, R01-CA-76016,CA-58860, CA-92044, P50 CA83636), Department of Defense (W81XWH-06-1-0220, W81XWH-09-OCRP-CONDEV), American Cancer Society California Division (S10P-06-258-01-CCE), Mayo Foundation, L&S Milken Family Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | GROWTH-FACTOR-BETA, GENOME-WIDE ASSOCIATION, MAMMARY-GLAND, TGF-BETA, ORAL-CONTRACEPTIVES, EXPRESSION, DECORIN, RISK, CARCINOMA, TRENDS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1309714 |
Archive Staff Only
 |
View Item |
