Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Highly Accessed Research article

Novel genetic variants in miR-191 gene and familial ovarian cancer

Jie Shen1, Richard DiCioccio2, Kunle Odunsi3, Shashikant B Lele3 and Hua Zhao1*

Author Affiliations

1 Department of Cancer Prevention and Controls, Roswell Park Cancer Institute, Buffalo, NY 14263, USA

2 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA

3 Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA

For all author emails, please log on.

BMC Cancer 2010, 10:47  doi:10.1186/1471-2407-10-47

Published: 18 February 2010

Abstract

Background

Half of the familial aggregation of ovarian cancer can't be explained by any known risk genes, suggesting the existence of other genetic risk factors. Some of these unknown factors may not be traditional protein encoding genes. MicroRNA (miRNA) plays a critical role in tumorigenesis, but it is still unknown if variants in miRNA genes lead to predisposition to cancer. Considering the fact that miRNA regulates a number of tumor suppressor genes (TSGs) and oncogenes, genetic variations in miRNA genes could affect the levels of expression of TSGs or oncogenes and, thereby, cancer risk.

Methods and Results

To test this hypothesis in familial ovarian cancer, we screened for genetic variants in thirty selected miRNA genes, which are predicted to regulate key ovarian cancer genes and are reported to be misexpressed in ovarian tumor tissues, in eighty-three patients with familial ovarian cancer. All of the patients are non-carriers of any known BRCA1/2 or mismatch repair (MMR) gene mutations. Seven novel genetic variants were observed in four primary or precursor miRNA genes. Among them, three rare variants were found in the precursor or primary precursor of the miR-191 gene. In functional assays, the one variant located in the precursor of miR-191 resulted in conformational changes in the predicted secondary structures, and consequently altered the expression of mature miR-191. In further analysis, we found that this particular variant exists in five family members who had ovarian cancer.

Conclusions

Our findings suggest that there are novel genetic variants in miRNA genes, and those certain genetic variants in miRNA genes can affect the expression of mature miRNAs and, consequently, might alter the regulation of TSGs or oncogenes. Additionally, the variant might be potentially associated with the development of familial ovarian cancer.