Cargando…
Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers
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 SNP28...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519699/ https://www.ncbi.nlm.nih.gov/pubmed/23039163 http://dx.doi.org/10.1186/1471-2407-12-454 |
_version_ | 1782252717319651328 |
---|---|
author | Bjørnslett, Merete Knappskog, Stian Lønning, Per Eystein Dørum, Anne |
author_facet | Bjørnslett, Merete Knappskog, Stian Lønning, Per Eystein Dørum, Anne |
author_sort | Bjørnslett, Merete |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3519699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35196992012-12-12 Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers Bjørnslett, Merete Knappskog, Stian Lønning, Per Eystein Dørum, Anne BMC Cancer Research Article 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. BioMed Central 2012-10-05 /pmc/articles/PMC3519699/ /pubmed/23039163 http://dx.doi.org/10.1186/1471-2407-12-454 Text en Copyright ©2012 Bjørnslett et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Bjørnslett, Merete Knappskog, Stian Lønning, Per Eystein Dørum, Anne Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers |
title | Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers |
title_full | Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers |
title_fullStr | Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers |
title_full_unstemmed | Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers |
title_short | Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers |
title_sort | effect of the mdm2 promoter polymorphisms snp309t>g and snp285g>c on the risk of ovarian cancer in brca1 mutation carriers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519699/ https://www.ncbi.nlm.nih.gov/pubmed/23039163 http://dx.doi.org/10.1186/1471-2407-12-454 |
work_keys_str_mv | AT bjørnslettmerete effectofthemdm2promoterpolymorphismssnp309tgandsnp285gcontheriskofovariancancerinbrca1mutationcarriers AT knappskogstian effectofthemdm2promoterpolymorphismssnp309tgandsnp285gcontheriskofovariancancerinbrca1mutationcarriers AT lønningpereystein effectofthemdm2promoterpolymorphismssnp309tgandsnp285gcontheriskofovariancancerinbrca1mutationcarriers AT dørumanne effectofthemdm2promoterpolymorphismssnp309tgandsnp285gcontheriskofovariancancerinbrca1mutationcarriers |