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
Por:
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, Thomassen, M, Paligo, M, Aretini, P, 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, Benitez, J, Gilbert, M, Rookus, M, Aalfs, CM, Kluijt, I, Boessenkool-Pape, JL, Meijers-Heijboer, HEJ, Oosterwijk, JC, van Asperen, CJ, Blok, MJ, Nelen, MR, van den Ouweland, AMW, Seynaeve, C, van der Luijt, RB, Devilee, P, 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, 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, O, 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, 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
Publicada:
5 jun 2012
Resumen:
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. British Journal of Cancer (2012) 106, 2016-2024. doi:10.1038/bjc.2012.160 www.bjcancer.com Published online 15 May 2012 (C) 2012 Cancer Research UK
Filiaciones:
Jakubowska, A:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Rozkrut, D:
Univ Szczecin, Sch Econ & Management, Dept Stat & Econometr, Szczecin, Poland
Antoniou, A:
Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England
Hamann, U:
Deutsch Krebsforschungszentrum DKFZ, Dept Funct Genome Anal, Heidelberg, Germany
Scott, RJ:
Univ Newcastle, Dept Med Genet, Fac Hlth, Callaghan, NSW 2308, Australia
Hunter Med Res Inst, Newcastle, NSW, Australia
McGuffog, L:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England
Healy, S:
Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia
Sinilnikova, OM:
Ctr Hosp Univ Lyon, Unite Mixte Genet Constitut Canc Frequents, Hosp Civil Lyon, Ctr Leon Berard Lyon, Lyon, France
Univ Lyon 1, INSERM, CNRS, U1052,UMR5286,Ctr Rech Cancerol Lyon, F-69365 Lyon, France
Rennert, G:
Technion Israel Inst Technol, Dept Community Med & Epidemiol, Haifa, Israel
Technion Israel Inst Technol, Clalit Natl Canc Control Ctr, Carmel Med Ctr, Haifa, Israel
Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel
Lejbkowicz, F:
Technion Israel Inst Technol, Dept Community Med & Epidemiol, Haifa, Israel
Technion Israel Inst Technol, Clalit Natl Canc Control Ctr, Carmel Med Ctr, Haifa, Israel
Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel
Flugelman, A:
Technion Israel Inst Technol, Dept Community Med & Epidemiol, Haifa, Israel
Technion Israel Inst Technol, Clalit Natl Canc Control Ctr, Carmel Med Ctr, Haifa, Israel
Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel
Andrulis, IL:
Canc Care Ontario, Dept Mol Genet, Ontario Canc Genet Network, Toronto, ON, Canada
Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
Glendon, G:
Canc Care Ontario, Dept Mol Genet, Ontario Canc Genet Network, Toronto, ON, Canada
Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
Ozcelik, H:
Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
Thomassen, M:
Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark
Paligo, M:
Univ Hosp Pisa, Sect Genet Oncol, Pisa, Italy
Aretini, P:
Univ Hosp Pisa, Sect Genet Oncol, Pisa, Italy
Kantala, J:
Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden
Aroer, B:
Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden
Von Wachenfeldt, A:
Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden
Liljegren, A:
Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden
Loman, N:
Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden
Herbst, K:
Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden
Kristoffersson, U:
Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden
Rosenquist, R:
Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, Uppsala, Sweden
Karlsson, P:
Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden
Stenmark-Askmalm, M:
Linkoping Univ Hosp, Dept Oncol, S-58185 Linkoping, Sweden
Melin, B:
Umea Univ, Dept Radiat Sci, Umea, Sweden
Nathanson, KL:
Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA
Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA
Domchek, SM:
Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA
Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA
Byrski, T:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Huzarski, T:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Gronwald, J:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Menkiszak, J:
Pomeranian Med Univ, Chair & Dept Surg Gynecol, Szczecin, Poland
Cybulski, C:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Serrano, P:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Osorio, A:
Spanish Natl Canc Res Ctr, Human Genet Grp, Madrid, Spain
Spanish Natl Canc Res Ctr, Genotyping Unit, Human Canc Genet Programme, Madrid, Spain
Cajal, TR:
Hosp Santa Creu & Sant Pau, Oncol Serv, E-08025 Barcelona, Spain
Tsitlaidou, M:
Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, IRRP, Athens 15310, Greece
Benitez, J:
Spanish Natl Canc Res Ctr, Human Genet Grp, Madrid, Spain
Spanish Natl Canc Res Ctr, Genotyping Unit, Human Canc Genet Programme, Madrid, Spain
Gilbert, M:
Deutsch Krebsforschungszentrum DKFZ, Dept Funct Genome Anal, Heidelberg, Germany
Rookus, M:
Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands
Aalfs, CM:
Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands
Kluijt, I:
Netherlands Canc Inst, Dept Family Canc Clin, Amsterdam, Netherlands
Boessenkool-Pape, JL:
Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands
Meijers-Heijboer, HEJ:
Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands
Oosterwijk, JC:
Univ Groningen, Univ Med Ctr, Dept Genet, Groningen, Netherlands
van Asperen, CJ:
Leiden Univ Med Ctr, Dept Clin Genet, Leiden, Netherlands
Blok, MJ:
Univ Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands
Nelen, MR:
Radboud Univ Nijmegen Med Ctr, Dept Human Genet 849, NL-6500 HB Nijmegen, Netherlands
van den Ouweland, AMW:
Erasmus MC, Dept Clin Genet, Family Canc Clin, Rotterdam, Netherlands
Seynaeve, C:
Erasmus MC, Dept Med Oncol, Family Canc Clin, Rotterdam, Netherlands
van der Luijt, RB:
Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands
Devilee, P:
Leiden Univ Med Ctr, Dept Human Genet, Leiden, Netherlands
Leiden Univ Med Ctr, Dept Pathol, Leiden, Netherlands
Easton, DF:
Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Peock, S:
Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Frost, D:
Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Platte, R:
Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Ellis, SD:
Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Fineberg, E:
Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Evans, DG:
NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp, Manchester, Lancs, England
Lalloo, F:
NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp, Manchester, Lancs, England
Eeles, R:
Royal Marsden NHS Fdn Trust, London, England
Jacobs, C:
Guys & St Thomas NHS Fdn Trust, London, England
Adlard, J:
Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England
Davidson, R:
Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland
Eccles, D:
Univ Southampton, Fac Med, Southampton Univ Hosp NHS Trust, Southampton SO9 5NH, Hants, England
Cole, T:
Birmingham Womens Hosp Healthcare NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England
Cook, J:
Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England
Godwin, A:
Univ Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA
Bove, B:
Fox Chase Canc Ctr, Clin Mol Genet Lab, Philadelphia, PA 19111 USA
Stoppa-Lyonnet, D:
Inst Curie, Serv Genet Oncol, Dept Biol Tumeurs, Paris, France
Inst Curie, Unite INSERM U830, Paris, France
Univ Paris 05, Fac Med, Paris, France
Caux-Moncoutier, V:
Inst Curie, Serv Genet Oncol, Dept Biol Tumeurs, Paris, France
Belotti, M:
Inst Curie, Serv Genet Oncol, Dept Biol Tumeurs, Paris, France
Tirapo, C:
Inst Curie, Serv Genet Oncol, Dept Biol Tumeurs, Paris, France
Mazoyer, S:
Univ Lyon 1, INSERM, CNRS, U1052,UMR5286,Ctr Rech Cancerol Lyon, F-69365 Lyon, France
Barjhoux, L:
Univ Lyon 1, INSERM, CNRS, U1052,UMR5286,Ctr Rech Cancerol Lyon, F-69365 Lyon, France
Boutry-Kryza, N:
Ctr Hosp Univ Lyon, Unite Mixte Genet Constitut Canc Frequents, Hosp Civil Lyon, Ctr Leon Berard Lyon, Lyon, France
Pujol, P:
CHU Arnaud de Villeneuve, Unite Oncogenet, Montpellier, France
CRCM dAurelle, INSERM 896, Montpellier, France
Coupier, I:
CHU Arnaud de Villeneuve, Unite Oncogenet, Montpellier, France
CRLCC Val dAurelle, Unite Oncogenet, Montpellier, France
Peyrat, JP:
Ctr Oscar Lambret, Lab Oncol Mol Humaine, F-59020 Lille, France
Vennin, P:
Ctr Oscar Lambret, Consultat Oncogenet, F-59020 Lille, France
Muller, D:
CLCC Paul Strauss, Unite Oncogenet, Strasbourg, France
Fricker, JP:
CLCC Paul Strauss, Unite Oncogenet, Strasbourg, France
Venat-Bouvet, L:
Ctr Hosp Univ Dupuytren, Dept Med Oncol, Limoges, France
Johannsson, O:
Landspitali Univ Hosp, Dept Oncol, Reykjavik, Iceland
Univ Iceland, Fac Med, Reykjavik, Iceland
Isaacs, C:
Georgetown Univ, Dept Med & Oncol, Washington, DC USA
Schmutzler, R:
Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany
Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany
Wappenschmidt, B:
Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany
Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany
Meindl, A:
Univ Munich, Dept Obstet & Gynaecol, Munich, Germany
Arnold, N:
Univ Kiel, Dept Obstet & Gynaecol, Univ Hosp Schleswig Holstein, D-24098 Kiel, Germany
Varon-Mateeva, R:
Inst Human Genet, Charite Berlin, Germany
Niederacher, D:
Univ Dusseldorf, Dept Obstet & Gynaecol, Univ Hosp Dusseldorf, D-40225 Dusseldorf, Germany
Sutter, C:
Univ Heidelberg Hosp, Inst Human Genet, Dept Human Genet, Heidelberg, Germany
Deissler, H:
Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany
Preisler-Adams, S:
Univ Munster, Inst Human Genet, D-4400 Munster, Germany
Simard, J:
Univ Laval, Quebec City, PQ, Canada
Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada
Soucy, P:
Univ Laval, Quebec City, PQ, Canada
Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada
Durocher, F:
Univ Laval, Quebec City, PQ, Canada
Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada
Chenevix-Trench, G:
Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia
Beesley, J:
Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia
Chen, X:
Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia
Rebbeck, T:
Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA
Couch, F:
Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA
Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA
Wang, X:
Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA
Lindor, N:
Mayo Clin, Dept Med Genet, Rochester, MN USA
Fredericksen, Z:
Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA
Pankratz, VS:
Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA
Peterlongo, P:
Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predicted Med, Milan, Italy
Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy
Bonanni, B:
Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy
Fortuzzi, S:
Fdn Ist FIRC Oncol Mol, IFOM 82, Milan, Italy
84 Cogentech Canc Genet Test Lab, Milan, Italy
Peissel, B:
Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Prevent Med, Milan, Italy
Szabo, C:
Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA
Mai, PL:
Dept Hlth & Human Serv, Clin Genet Branch, Div Canc Epidemiol & Genet, NCI,NIH, Rockville, MD 20852 USA
Loud, JT:
Dept Hlth & Human Serv, Clin Genet Branch, Div Canc Epidemiol & Genet, NCI,NIH, Rockville, MD 20852 USA
Lubinski, J:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Hybrid Gold, Green Published
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