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.
Source: Effect
of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of
ovarian cancer in BRCA1 mutation carriers. Bjørnslett M, Knappskog S, Lønning
PE, Dørum A (anne.dorum@medisin.uio.no).
BMC Cancer. 2012 Oct 5;12(1):454.
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