Abstract
BackgroundThe variable penetrance of ovarian cancer in BRCA1 mutation carriers suggests that other genetic or environmental factors modify disease risk. The C to T transition in the 3' untranslated region of the prohibitin (PHB) gene alters mRNA function and has recently been shown to be associated with hereditary breast cancer risk in Polish women harbouring BRCA1 mutations.MethodsTo investigate whether the PHB 3'UTR polymorphism also modifies hereditary ovarian cancer risk, we performed a case-control study among Polish women carrying one of the three common founder mutations (5382insC, 300 T > G, 4154delA) including 127 ovarian cases and 127 unaffected controls who had both breasts and ovaries intact. Controls were matched to cases by year of birth and BRCA1 mutation. Genotyping analysis was performed using PCR-based restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using conditional and penalized univariable and multivariable logistic regression.ResultsA comparison of the genotype frequencies between cases and controls revealed no association of the PHB 3'UTR _CT+TT genotypes with ovarian cancer risk (ORadj 1.34; 95% CI, 0.59–3.11).ConclusionOur data suggest that the PHB 3'UTR polymorphism does not modify ovarian cancer risk in women carrying one of the three Polish BRCA1 founder mutations.
Highlights
The variable penetrance of ovarian cancer in BRCA1 mutation carriers suggests that other genetic or environmental factors modify disease risk
Our data suggest that the PHB 3'untranslated region (3'UTR) polymorphism does not modify ovarian cancer risk in women carrying one of the three Polish BRCA1 founder mutations
A functional single nucleotide polymorphism (SNP) in the PHB gene changing a cytosine to a thymine at position 1630 in the 3'UTR has been identified that lacks the antiproliferative activity [7] and significantly reduces cell motility [9]
Summary
The variable penetrance of ovarian cancer in BRCA1 mutation carriers suggests that other genetic or environmental factors modify disease risk. The C to T transition in the 3' untranslated region of the prohibitin (PHB) gene alters mRNA function and has recently been shown to be associated with hereditary breast cancer risk in Polish women harbouring BRCA1 mutations. Women harboring BRCA1 germ line mutations have a high life time risk of developing ovarian cancer, ranging from 16% in specific ethnic groups [1] to 63% in highly selected families with multiple affected individuals [2]. These differences suggest that the penetrance of BRCA1 mutations is modified by other genetic and/or environmental factors. A functional single nucleotide polymorphism (SNP) in the PHB gene changing a cytosine to a thymine at position 1630 in the 3'UTR (rs6917) has been identified that lacks the antiproliferative activity [7] and significantly reduces cell motility [9]
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