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Title: Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study.
Authors: Jakubowska A,  Rozkrut D,  Antoniou A,  Hamann U,  Scott RJ,  McGuffog L,  Healy S,  Sinilnikova OM,  Rennert G,  Lejbkowicz F,  Flugelman A,  Andrulis IL,  Glendon G,  Ozcelik H,  OCGN,  Thomassen M,  Paligo M,  Aretini P,  SWE-BRCA,  Kantala J,  Aroer B,  von Wachenfeldt A,  Liljegren A,  Loman N,  Herbst K,  Kristoffersson U,  Rosenquist R,  Karlsson P,  Stenmark-Askmalm M,  Melin B,  Nathanson KL,  Domchek SM,  Byrski T,  Huzarski T,  Gronwald J,  Menkiszak J,  Cybulski C,  Serrano P,  Osorio A,  Cajal TR,  Tsitlaidou M,  Benítez J,  Gilbert M,  HEBON,  Rookus M,  Aalfs CM,  Kluijt I,  Boessenkool-Pape JL,  Meijers-Heijboer HE,  Oosterwijk JC,  van Asperen CJ,  Blok MJ,  Nelen MR,  van den Ouweland AM,  Seynaeve C,  van der Luijt RB,  Devilee P,  EMBRACE,  Easton DF,  Peock S,  Frost D,  Platte R,  Ellis SD,  Fineberg E,  Evans DG,  Lalloo F,  Eeles R,  Jacobs C,  Adlard J,  Davidson R,  Eccles D,  Cole T,  Cook J,  Godwin A,  Bove B,  GEMO Study Collaborators,  Stoppa-Lyonnet D,  Caux-Moncoutier V,  Belotti M,  Tirapo C,  Mazoyer S,  Barjhoux L,  Boutry-Kryza N,  Pujol P,  Coupier I,  Peyrat JP,  Vennin P,  Muller D,  Fricker JP,  Venat-Bouvet L,  Johannsson OT,  Isaacs C,  Schmutzler R,  Wappenschmidt B,  Meindl A,  Arnold N,  Varon-Mateeva R,  Niederacher D,  Sutter C,  Deissler H,  Preisler-Adams S,  Simard J,  Soucy P,  Durocher F,  Chenevix-Trench G,  Beesley J,  Chen X,  KConFab,  Rebbeck T,  Couch F,  Wang X,  Lindor N,  Fredericksen Z,  Pankratz VS,  Peterlongo P,  Bonanni B,  Fortuzzi S,  Peissel B,  Szabo C,  Mai PL,  Loud JT,  Lubinski J,  CIMBA, the Consortium of Investigators of Modifiers of BRCA1/2-Related Cancer
Journal: Br J Cancer
Date: 2012 Jun 5
Branches: CGB
PubMed ID: 22669161
PMC ID: PMC3388557
Abstract: BACKGROUND: The 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. METHODS: To 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. RESULTS: There 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. CONCLUSION: The 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.