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, Rodney; 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.; van der Luijt, B.; Devilee, P.; EMBRACE,; 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.; GEMO Study Collaborators,; Stoppa-Lyonnet, D.; Caux-Moncoutier, V.; 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.; ConFab, K.; 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.; 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.; Benitez, 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.

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

journal contribution

posted on 2025-05-09, 12:14 authored by A. Jakubowska, D. Rozkrut, A. Antoniou, U. Hamann, Rodney ScottRodney Scott, L. McGuffog, S. Healy, O. M. Sinilnikova, G. Rennert, F. Lejbkowicz, A. Flugelman, I. L. Andrulis, G. Glendon, H. Ozcelik, M. Thomassen, M. Paligo, P. Aretini, J. Kantala, B. Aroer, A. Von Wachenfeldt, B. van der Luijt, P. Devilee, EMBRACE, D. F. Easton, S. Peock, D. Frost, R. Platte, S. D. Ellis, E. Fineberg, D. G. Evans, F. Lalloo, R. Eeles, C. Jacobs, J. Adlard, R. Davidson, D. Eccles, T. Cole, J. Cook, A. Godwin, B. Bove, GEMO Study Collaborators, D. Stoppa-Lyonnet, V. Caux-Moncoutier, I. Coupier, J.-P. Peyrat, P. Vennin, D. Muller, J. P. Fricker, L. Venat-Bouvet, O. Th. Johannsson, C. Isaacs, R. Schmutzler, B. Wappenschmidt, A. Meindl, N. Arnold, R. Varon-Mateeva, D. Niederacher, C. Sutter, H. Deissler, S. Preisler-Adams, J. Simard, P. Soucy, F. Durocher, G. Chenevix-Trench, J. Beesley, X. Chen, K. ConFab, T. Rebbeck, F. Couch, X. Wang, N. Lindor, Z. Fredericksen, V. S. Pankratz, P. Peterlongo, B. Bonanni, S. Fortuzzi, B. Peissel, C. Szabo, P. L. Mai, J. T. Loud, J. Lubinski, A. Liljegren, N. Loman, K. Herbst, U. Kristoffersson, R. Rosenquist, P. Karlsson, M. Stenmark-Askmalm, B. Melin, K. L. Nathanson, S. M. Domchek, T. Byrski, T. Huzarski, J. Gronwald, J. Menkiszak, C. Cybulski, P. Serrano, A. Osorio, T. R. Cajal, M. Tsitlaidou, J. Benitez, M. Gilbert, M. Rookus, C. M. Aalfs, I. Kluijt, J. L. Boessenkool-Pape, H. E. J. Meijers-Heijboer, J. C. Oosterwijk, C. J. Van Asperen, M. J. Blok, M. R. Nelen, A. M. W. Van Den Ouweland, C. Seynaeve

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.

History

Journal title

British Journal of Cancer

Volume

106

Issue

12

Pagination

2016-2024

Publisher

Nature Publishing Group

Place published

London, UK

Language

en, English

College/Research Centre

Faculty of Health

School

School of Biomedical Sciences and Pharmacy

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