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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

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
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 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.
0007-0920
2016-2024
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Chen, X.
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Rebbeck, T.
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Couch, F.
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Wang, X.
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Lindor, N.
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Fredericksen, Z.
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Pankratz, V.S.
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Peterlongo, P.
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Bonanni, B.
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Fortuzzi, S.
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Peissel, B.
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Szabo, C.
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Mai, P.L.
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Loud, J.T.
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Lubinski, J.
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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. and Lubinski, J. (2012) 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. British Journal of Cancer, 106 (12), 2016-2024. (doi:10.1038/bjc.2012.160). (PMID:22669161)

Record type: Article

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.

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Published date: 15 May 2012
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 352309
URI: http://eprints.soton.ac.uk/id/eprint/352309
DOI: doi:10.1038/bjc.2012.160
ISSN: 0007-0920
PURE UUID: 7869ef0e-4321-4094-bed2-c8e96da7c6d2
ORCID for D. Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 09 May 2013 11:30
Last modified: 15 Mar 2024 02:40

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Contributors

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

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