BMC Cancer 2008, 8:90 http://www.biomedcentral.com/1471-2407/8/90 Comparison of PHB 3'UTR T allele and genotype frequencies among ovarian cancer cases and controls Among BRCA1 carriers, no difference in the T allele fre- quency between ovarian cancer cases and controls was observed (27/254, 11%; 95% CI 7.12–15.10 vs. 25/254, 10%, 95% CI 6.50–14.20) (Fisher's exact test, p = 0.88). The genotype distribution among all case-control pairs (n = 127) and among those with risk factor information (n = 83) are shown in Table 2. There was no difference in CT+TT genotype frequencies among cases and controls (ORcrude, 1.05; 95% CI, 0.54–2.04; ORadj, 1.34; 95% CI 0.59–3.11). After exclusion of related study subjects, sim- ilar results were obtained (ORcrude, 1.06; 95% CI 0.55– 2.01; ORadj, 1.38; 95% CI 0.57–3.41). Among all cases, women with the CT+TT genotypes were diagnosed at a median age one year younger than women with the CC genotype [45 years (range 35–71 years) vs. 46 years (range 25–71 years)], but this age difference was not statistically significant (Mann-Whitney test, p = 0.77). Discussion In the present study we investigated the effect of PHB 3'UTR polymorphism on the risk of ovarian cancer in BRCA1 mutation carriers. While one investigation of the PHB polymorphism in an ovarian cancer population has been previously reported [19], nothing is known about its' influence in women with predisposing mutations in the BRCA1 gene. In this matched case-control study we did not find an association of the PHB CT+TT genotypes with ovarian cancer risk in selected women harbouring one of the path- ogenic BRCA1 founder mutations. This result remained after adjusting for known and putative ovarian cancer risk factors including age at menarche, age of first live birth, parity, breastfeeding, OC use, HRT, smoking status and BMI [20,21] as well as after exclusion of those study par- ticipants who were related to one another suggesting that confounding due to these variables was unlikely. Outside the context of hereditary ovarian cancer there is only one Australian study that has investigated the contri- bution of the PHB 3'UTR polymorphism to ovarian cancer risk. In this case-control study on 553 ovarian cancer cases and 300 unaffected controls also no association of the CT+TT genotypes with ovarian cancer risk has been found [19]. When taken together, it appears that our results and those reported by Spurdle et al. [19] do not support a role for PHB polymorphism in sporadic and hereditary ovar- ian cancer risk. This finding is in contrast to our observation that the PHB polymorphism acts as a modifier of BRCA1-associated breast cancer risk in a similar collective of 258 breast can- cer patients and 258 matched controls [10]. The most likely explanation for the difference of effect between breast cancer and ovarian cancer patients within our study set is in the underlying disease mechanisms involved in breast cancer compared to ovarian cancer. At this stage what these differences are remains to be resolved. How- ever, it also cannot be ruled out that due to the smaller size of the ovarian cancer study no association was detected. Thus, larger studies are warranted to confirm these preliminary results. Conclusion In summary, the 3'UTR polymorphism in PHB appears not to be associated with ovarian cancer risk in women carrying of one of the three Polish BRCA1 founder muta- Table 2: Association of the PHB_1630_C > T polymorphism with ovarian cancer risk in BRCA1 carriers 102 (80) 25 (20) 65 (78) 18 (18) ORcrudeb (95% CI) 1.00 (reference) 1.05 (0.54–2.04) ORadjc (95% CI) 1.00(reference) 1.34 (0.59–3.11) p 1.00 p 0.49 Page 4 of 5 (page number not for citation purposes) Genotype PHB_1630_C > T CC CT+TTa Genotype PHB_1630_C > T CC CT+TTa a Due to the low proportion of <3% in patients and controls, CT and TT genotypes were combined. b ORcrude: crude odds ratio. c ORadj: odds ratio adjusted for age at menarche, age of first live birth, parity, breastfeeding, OC use, HRT, smoking and BMI. 101 (80) 26 (20) 64 (77) 19 (23) All cases and controls Cases (n = 127) n (%) Controls (n = 127) n (%) Cases and controls with risk factor information Cases (n = 83) n (%) Controls (n = 83) n (%)