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Open Access Research article

Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers

Merete Bjørnslett12, Stian Knappskog34, Per Eystein Lønning34 and Anne Dørum56*

Author Affiliations

1 Department of Medical Genetics, Oslo University Hospital – The Norwegian Radium Hospital, Oslo, Norway

2 Institute of Clinical Medicine, University of Oslo, Oslo, Norway

3 Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway

4 Department of Oncology, Haukeland University Hospital, Bergen, Norway

5 Department of Gynecological Oncology, Oslo University Hospital – The Norwegian Radium Hospital, PO Box 4953, Nydalen, N-0424, Oslo, Norway

6 Faculty of Medicine, University of Oslo, Oslo, Norway

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BMC Cancer 2012, 12:454  doi:10.1186/1471-2407-12-454

Published: 5 October 2012

Abstract

Background

While BRCA mutation carriers possess a 20-40% lifetime risk of developing ovarian cancer, knowledge about genetic modifying factors influencing the phenotypic expression remains obscure. We explored the distribution of the MDM2 polymorphisms SNP309T>G and the recently discovered SNP285G>C in Norwegian patients with BRCA related ovarian cancer.

Methods

221 BRCA related ovarian cancer cases (BRCA1; n = 161 and BRCA2; n = 60) were tested for the MDM2 polymorphisms. Results were compared to healthy controls (n = 2,465).

Results

The SNP309G allele was associated with elevated OR for ovarian cancer in BRCA1 mutation carriers (SNP309TG: OR 1.53; CI 1.07-2.19; p = 0.020; SNP309GG: OR 1.92; CI 1.19-3.10; p = 0.009; SNP309TG+GG combined: OR 1.61; CI 1.15-2.27; p = 0.005). In contrast, the SNP285C allele reduced risk of BRCA1 related ovarian cancer in carriers of the SNP309G allele (OR 0.50; CI 0.24-1.04; p = 0.057). Censoring individuals carrying the SNP285C/309G haplotype from the analysis elevated the OR related to the SNP309G allele (OR 1.73; CI 1.23-2.45; p = 0.002). The mean age at disease onset was 3.1 years earlier in carriers of SNP309TG+GG as compared to carriers of SNP309TT (p = 0.068). No such associations were found in BRCA2 related ovarian cancer.

Conclusions

Our results indicate the SNP309G allele to increase and the SNP285C allele to reduce the risk of BRCA1 related ovarian cancer. If confirmed in independent studies, this finding may have implications to counseling and decision-making regarding risk reducing measures in BRCA1 mutation carriers.

Keywords:
Ovarian cancer; BRCA; MDM2 SNP285; MDM2 SNP309