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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
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 di...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388557/ https://www.ncbi.nlm.nih.gov/pubmed/22669161 http://dx.doi.org/10.1038/bjc.2012.160 |
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author | Jakubowska, A Rozkrut, D Antoniou, A Hamann, U Scott, R J McGuffog, L Healy, S Sinilnikova, O M Rennert, G Lejbkowicz, F Flugelman, A Andrulis, I L 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, K L Domchek, S M Byrski, T Huzarski, T Gronwald, J Menkiszak, J Cybulski, C Serrano, P Osorio, A Cajal, T R Tsitlaidou, M Benítez, J Gilbert, M Rookus, M Aalfs, C M Kluijt, I Boessenkool-Pape, J L Meijers-Heijboer, H E J Oosterwijk, J C van Asperen, C J Blok, M J Nelen, M R van den Ouweland, A M W Seynaeve, C van der Luijt, R B Devilee, P Easton, D F Peock, S Frost, D Platte, R Ellis, S D Fineberg, E Evans, D G 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, J-P Vennin, P Muller, D Fricker, J-P Venat-Bouvet, L Johannsson, O Th 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, V S Peterlongo, P Bonanni, B Fortuzzi, S Peissel, B Szabo, C Mai, P L Loud, J T Lubinski, J |
author_facet | Jakubowska, A Rozkrut, D Antoniou, A Hamann, U Scott, R J McGuffog, L Healy, S Sinilnikova, O M Rennert, G Lejbkowicz, F Flugelman, A Andrulis, I L 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, K L Domchek, S M Byrski, T Huzarski, T Gronwald, J Menkiszak, J Cybulski, C Serrano, P Osorio, A Cajal, T R Tsitlaidou, M Benítez, J Gilbert, M Rookus, M Aalfs, C M Kluijt, I Boessenkool-Pape, J L Meijers-Heijboer, H E J Oosterwijk, J C van Asperen, C J Blok, M J Nelen, M R van den Ouweland, A M W Seynaeve, C van der Luijt, R B Devilee, P Easton, D F Peock, S Frost, D Platte, R Ellis, S D Fineberg, E Evans, D G 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, J-P Vennin, P Muller, D Fricker, J-P Venat-Bouvet, L Johannsson, O Th 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, V S Peterlongo, P Bonanni, B Fortuzzi, S Peissel, B Szabo, C Mai, P L Loud, J T Lubinski, J |
author_sort | Jakubowska, A |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3388557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-33885572013-06-05 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 Jakubowska, A Rozkrut, D Antoniou, A Hamann, U Scott, R J McGuffog, L Healy, S Sinilnikova, O M Rennert, G Lejbkowicz, F Flugelman, A Andrulis, I L 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, K L Domchek, S M Byrski, T Huzarski, T Gronwald, J Menkiszak, J Cybulski, C Serrano, P Osorio, A Cajal, T R Tsitlaidou, M Benítez, J Gilbert, M Rookus, M Aalfs, C M Kluijt, I Boessenkool-Pape, J L Meijers-Heijboer, H E J Oosterwijk, J C van Asperen, C J Blok, M J Nelen, M R van den Ouweland, A M W Seynaeve, C van der Luijt, R B Devilee, P Easton, D F Peock, S Frost, D Platte, R Ellis, S D Fineberg, E Evans, D G 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, J-P Vennin, P Muller, D Fricker, J-P Venat-Bouvet, L Johannsson, O Th 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, V S Peterlongo, P Bonanni, B Fortuzzi, S Peissel, B Szabo, C Mai, P L Loud, J T Lubinski, J Br J Cancer Genetics and Genomics 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. Nature Publishing Group 2012-06-05 2012-05-15 /pmc/articles/PMC3388557/ /pubmed/22669161 http://dx.doi.org/10.1038/bjc.2012.160 Text en Copyright © 2012 Cancer Research UK https://creativecommons.org/licenses/by-nc-sa/3.0/From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Genetics and Genomics Jakubowska, A Rozkrut, D Antoniou, A Hamann, U Scott, R J McGuffog, L Healy, S Sinilnikova, O M Rennert, G Lejbkowicz, F Flugelman, A Andrulis, I L 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, K L Domchek, S M Byrski, T Huzarski, T Gronwald, J Menkiszak, J Cybulski, C Serrano, P Osorio, A Cajal, T R Tsitlaidou, M Benítez, J Gilbert, M Rookus, M Aalfs, C M Kluijt, I Boessenkool-Pape, J L Meijers-Heijboer, H E J Oosterwijk, J C van Asperen, C J Blok, M J Nelen, M R van den Ouweland, A M W Seynaeve, C van der Luijt, R B Devilee, P Easton, D F Peock, S Frost, D Platte, R Ellis, S D Fineberg, E Evans, D G 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, J-P Vennin, P Muller, D Fricker, J-P Venat-Bouvet, L Johannsson, O Th 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, V S Peterlongo, P Bonanni, B Fortuzzi, S Peissel, B Szabo, C Mai, P L Loud, J T Lubinski, J 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 |
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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Genetics and Genomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388557/ https://www.ncbi.nlm.nih.gov/pubmed/22669161 http://dx.doi.org/10.1038/bjc.2012.160 |
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associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT barjhouxl associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT boutrykryzan associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT pujolp associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT coupieri associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT peyratjp associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT venninp associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT mullerd associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT frickerjp associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT venatbouvetl associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT johannssonoth associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT isaacsc associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT schmutzlerr associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT wappenschmidtb associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT meindla associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT arnoldn associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT varonmateevar associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT niederacherd associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT sutterc associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT deisslerh associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT preisleradamss associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT simardj associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT soucyp associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT durocherf associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT chenevixtrenchg associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT beesleyj associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT chenx associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT rebbeckt associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT couchf associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT wangx associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT lindorn associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT fredericksenz associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT pankratzvs associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT peterlongop associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT bonannib associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT fortuzzis associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT peisselb associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT szaboc associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT maipl associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT loudjt associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy AT lubinskij associationofphb1630ctandmthfr677ctpolymorphismswithbreastandovariancancerriskinbrca12mutationcarriersresultsfromamulticenterstudy |