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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Jakubowska
Anna
A
Pomeranian Medical University, Department of Genetics and Pathology, ul. Polabska 4, 70-115 Szczecin, Poland. aniaj@sci.pam.szczecin.pl
Gronwald
Jacek
J
Menkiszak
Janusz
J
Górski
Bohdan
B
Huzarski
Tomasz
T
Byrski
Tomasz
T
Benner
Axel
A
Lubiński
Jan
J
Scott
Rodney J
RJ
Hamann
Ute
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008423:Maternal Age; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D011044:Poland / Q000453:epidemiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D000091402:Prohibitins; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D044465:White People / Q000235:genetics*
C000717328:PHB protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases