Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

BackgroundThe variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity.MethodsTo evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively.ResultsThere was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10-2.04 and HR 2.16, 95%CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele.ConclusionThe PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers.

Original publication

DOI

10.1038/bjc.2012.160

Type

Journal article

Journal

British journal of cancer

Publication Date

06/2012

Volume

106

Pages

2016 - 2024

Addresses

Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. aniaj@sci.pam.szczecin.pl

Keywords

OCGN, SWE-BRCA, HEBON, EMBRACE, GEMO Study Collaborators, KConFab, CIMBA, the Consortium of Investigators of Modifiers of BRCA1/2-Related Cancer, Humans, Breast Neoplasms, Ovarian Neoplasms, Genetic Predisposition to Disease, Methylenetetrahydrofolate Reductase (NADPH2), Repressor Proteins, Risk, Heterozygote, Mutation, Polymorphism, Genetic, Genes, BRCA1, Genes, BRCA2, Female