BMC Cancer 2008, 8:90 http://www.biomedcentral.com/1471-2407/8/90 Background 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 environ- mental 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 even- tuates 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 func- tional 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 anti- proliferative activity [7] and significantly reduces cell motility [9]. The T allele of the PHB 3'UTR polymorphism has recently been shown to be associated with an increased risk of breast cancer (ORadj, 2.12; 95% CI, 1.23–3.70) [10] in Polish women carrying one of the three common BRCA1 founder mutations that account for approximately 90% of all detected BRCA1 mutations detected in this country [11,12]. In a North-American study, the T allele was also associated with an increased risk of breast cancer, particu- larly in women with a breast cancer diagnosis before the age of 50 years who had at least one first-degree relative with the disease [13]. However, these findings were not reproduced in two other case-control studies conducted in Australia and Great Britain [14,15]. Since nothing is known about the influence of the PHB 3'UTR polymorphism on hereditary ovarian cancer risk, we performed a case-control study among Polish women carrying one of the three common BRCA1 founder muta- tions, comprising 127 ovarian cases and 127 matched controls. Methods Study participants The Hereditary Cancer Registry at the Pomeranian Medi- cal University in Szczecin, Poland contains clinical and epidemiological data collected from 1997 and 2002 from 1,940 individuals carrying one of the three common Polish BRCA1 founder mutations: 5382insC, 300 T > G and 4154delA. From the 1,940 registered BRCA1 mutation carriers, 254 female Polish carriers constituting 127 case-control pairs for whom DNA samples were available were selected for this study. Controls were matched to cases by year of birth (within 2 years), and BRCA1 mutation (5382insC, 300 T > G, 4154delA). They were included as controls if they were unaffected by any type of cancer and had not under- gone prophylactic mastectomy, adnexectomy or tubal ligation prior to the age at which ovarian cancer was diag- nosed in the corresponding case. They were considered as cases if they were diagnosed with invasive primary ovarian cancer (excluding borderline ovarian carcinoma) and had not undergone prophylactic mastectomy, adnexectomy or tubal ligation prior to the age of ovarian cancer diagnosis. The research was approved by the Ethics Committee of Pomeranian Medical University in Szczecin, Poland and all participants gave informed consent prior to enrolling in the study. All women received genetic counseling prior to and at the provision of their test results. Genotyping analysis Genotyping of the 1630_C > T polymorphism (rs6917) in the 3'UTR of the PHB gene (Genbank accession number NT_010783.13) in 254 BRCA1 mutation carriers was per- formed by PCR-based restriction fragment length poly- morphism analysis as previously described [10]. Genotyping was carried out by two independent person- nel who were blinded to the disease status of the samples. Several samples were sequenced on an ABI prism 377 DNA Sequencer (Perkin-Elmer, Foster City, USA) to con- firm the genotypes. The reproducibility of the genotyping data was assessed by repeated analysis of 40/254 (16%) randomly selected DNA samples. Concordance for these quality control samples was 100%. Genotypes were obtained for all 254 BRCA1 mutation carriers constituting PCR concordance rate of 100%. Statistical analysis Statistical modelling of the study on 127 ovarian cancer case-control pairs revealed a 55.3% power to detect an OR of 2.00 and an 81.5% power to detect an OR of 2.50. This is based on the assumption that the probability of observ- ing CT+TT genotypes among control patients is 0.2. For the correlation, phi, between matched case and control patients to observe these genotypes we assumed a value of phi = 0.2 according the recommendation of Dupont [16]. This power calculation further assumes the use of a Chi- Square test with a 0.05 significance level. Risk estimates for the development of ovarian cancer were calculated as odds ratios (ORcrude) with 95% confidence interval (CI) using a conditional logistic regression model by maximising the conditional likelihood for all 127 case- Page 2 of 5 (page number not for citation purposes)