期刊
CANCER RESEARCH
卷 71, 期 11, 页码 3896-3903出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-10-4167
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类别
资金
- Moffitt Cancer Center/University of South Florida
- Cancer Center [P30-CA0762-92]
- Mayo Foundation
- American Cancer Society [CRTG-00-196-01-CCE]
- Advanced Cancer Detection Center, Department of Defense [DAMD-17-98-1-8659]
- Canadian Cancer Society
- NIH [R01-CA-63682, R01-CA-63678]
- National Cancer Institute [P30-CA-15083]
- NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics
- Center for Cancer Research
- Cancer Research U.K.
- Eve Appeal
- OAK Foundation
- Department of Health's NIHR Biomedical Research Centre
- [R01-CA-114343]
- [R01-CA114343-S1]
- [R01-CA-122443]
- [P50-CA-136393]
- [R01-CA-76016]
- [R01-CA-106414]
- [CA-54419]
- [P50 CA105009]
- Medical Research Council [G0801875] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
- MRC [G0801875] Funding Source: UKRI
Defective microRNA (miRNA) biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNP) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P < 0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G>A), an SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR = 0.90, 95% CI: 0.82-0.98; P = 0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B overexpression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be because of reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility. Cancer Res; 71(11); 3896-903. (C) 2011 AACR.
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