Ovarian cancer risk in Polish BRCA1 mutation carriers is not associated with the prohibitin 3' untranslated region polymorphism

To 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.A 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).Our 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.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 candidate modifier of hereditary ovarian cancer risk is the prohibitin gene (PHB, OMIM 176705). The encoded gene product binds to the retinoblastoma protein, resulting in the suppression of E2F-mediated transcription, and the p53 tumor suppressor, which eventuates in increased p53-mediated transcriptional activity [3-5]. The 3'untranslated region (3'UTR) of the PHB gene encodes a tumor suppressive trans-acting regulatory RNA molecule [6] and acts as a cell cycle inhibitor between G1 and S phase when microinjected into normal mammary epithelial cells and other cancer cell lines [7,8]. A functional single nucleotide polymorphism (SNP) in the PHB gene changing a cytosine to a thymine at position 1630