期刊
PLOS ONE
卷 6, 期 5, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0019642
关键词
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资金
- National Health and Medical Research Council, Australia [199600]
- Cancer Council Tasmania, Australia
- Cancer Foundation of Western Australia, Australia
- National Cancer Plan - Action 29, Australia
- Alberta Heritage Foundation for Medical Research, Canada
- Worksafe BC, Canada
- Canadian Institutes of Health Research, Canada
- Michael Smith Foundation for Health Research, Canada
- Mermaid 1, Denmark
- Danish Cancer Society, Denmark
- Helsinki University Central Hospital, Finland
- Academy of Finland, Finland
- Finnish Cancer Society, Finland
- European Community, Germany [HEALTH-F2-2009-223175]
- Federal Ministry of Education and Research, Germany
- Programme of Clinical Biomedical Research, Germany [01 GB 9401]
- University of Ulm, Germany [P. 685]
- Radboud University Nijmegen Medical Centre, Netherlands
- municipality and community health service of Nijmegen, Netherlands
- Cancer Research UK, U.K.
- Association for International Cancer Research, U.K.
- St Andrews, U.K.
- Lon V. Smith Foundation, U.K. [LVS-39420]
- Eve Appeal, U.K.
- OAK Foundation, U.K.
- National Institute for Health Research Biomedical Research Centre, U.K.
- Ovarian Cancer Research Fund, U.S.
- National Institutes of Health, U.S. [R01-CA-61107, R01-CA-122443, R01-CA-76016, CA-58860, CA-92044, P50 CA83636]
- Department of Defense, U.S. [W81XWH-06-1-0220, W81XWH-09-OCRP-CONDEV]
- American Cancer Society California Division, U.S. [S10P-06-258-01-CCE]
- Mayo Foundation, U.S.
- L&S Milken Family Foundation, U.S.
- Cancer Research UK [13086] Funding Source: researchfish
- Medical Research Council [G0801875] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
- MRC [G0801875] Funding Source: UKRI
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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