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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

Jakubowska, A.; Rozkrut, D.; Antoniou, A.; Hamann, U.; Scott, R. J.; McGuffog, L.; Healy, S.; Sinilnikova, O. M.; Rennert, G. and Lejbkowicz, F., et al. (2012) In British Journal of Cancer 106(12). p.2016-2024
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,... (More)
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 (Less)
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BRCA1/2 mutation carriers, PHB 1630 C > T polymorphism, MTHFR 677 C > T, polymorphism, breast/ovarian cancer risk
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British Journal of Cancer
volume
106
issue
12
pages
2016 - 2024
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Nature Publishing Group
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  • wos:000305011100018
  • scopus:84862017252
ISSN
1532-1827
DOI
10.1038/bjc.2012.160
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English
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yes
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fc98ddf2-97e4-4cf7-b4a0-bc9bafea27ea (old id 2895941)
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2012-08-01 09:43:35
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2017-07-23 03:33:17
@article{fc98ddf2-97e4-4cf7-b4a0-bc9bafea27ea,
  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. 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},
  author       = {Jakubowska, A. and Rozkrut, D. and Antoniou, A. and Hamann, U. and Scott, R. J. and McGuffog, L. and Healy, S. and Sinilnikova, O. M. and Rennert, G. and Lejbkowicz, F. and Flugelman, A. and Andrulis, I. L. and Glendon, G. and Ozcelik, H. and Thomassen, M. and Paligo, M. and Aretini, P. and Kantala, J. and Aroer, B. and Von Wachenfeldt, A. and Liljegren, A. and Loman, Niklas and Herbst, K. and Kristoffersson, U. and Rosenquist, R. and Karlsson, P. and Stenmark-Askmalm, M. and Melin, B. and Nathanson, K. L. and Domchek, S. M. and Byrski, T. and Huzarski, T. and Gronwald, J. and Menkiszak, J. and Cybulski, C. and Serrano, P. and Osorio, A. and Cajal, T. R. and Tsitlaidou, M. and Benitez, J. and Gilbert, M. and Rookus, M. and Aalfs, C. M. and Kluijt, I. and Boessenkool-Pape, J. L. and Meijers-Heijboer, H. E. J. and Oosterwijk, J. C. and van Asperen, C. J. and Blok, M. J. and Nelen, M. R. and van den Ouweland, A. M. W. and Seynaeve, C. and van der Luijt, R. B. and Devilee, P. and Easton, D. F. and Peock, S. and Frost, D. and Platte, R. and Ellis, S. D. and Fineberg, E. and Evans, D. G. and Lalloo, F. and Eeles, R. and Jacobs, C. and Adlard, J. and Davidson, R. and Eccles, D. and Cole, T. and Cook, J. and Godwin, A. and Bove, B. and Stoppa-Lyonnet, D. and Caux-Moncoutier, V. and Belotti, M. and Tirapo, C. and Mazoyer, S. and Barjhoux, L. and Boutry-Kryza, N. and Pujol, P. and Coupier, I. and Peyrat, J-P and Vennin, P. and Muller, D. and Fricker, J-P and Venat-Bouvet, L. and Johannsson, OTh and Isaacs, C. and Schmutzler, R. and Wappenschmidt, B. and Meindl, A. and Arnold, N. and Varon-Mateeva, R. and Niederacher, D. and Sutter, C. and Deissler, H. and Preisler-Adams, S. and Simard, J. and Soucy, P. and Durocher, F. and Chenevix-Trench, G. and Beesley, J. and Chen, X. and Rebbeck, T. and Couch, F. and Wang, X. and Lindor, N. and Fredericksen, Z. and Pankratz, V. S. and Peterlongo, P. and Bonanni, B. and Fortuzzi, S. and Peissel, B. and Szabo, C. and Mai, P. L. and Loud, J. T. and Lubinski, J.},
  issn         = {1532-1827},
  keyword      = {BRCA1/2 mutation carriers,PHB 1630 C > T polymorphism,MTHFR 677 C > T,polymorphism,breast/ovarian cancer risk},
  language     = {eng},
  number       = {12},
  pages        = {2016--2024},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  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},
  url          = {http://dx.doi.org/10.1038/bjc.2012.160},
  volume       = {106},
  year         = {2012},
}