Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2

A. Osorio; R. L. Milne; R. Alonso; G. Pita; P. Peterlongo; A. Teule; K. L. Nathanson; S. M. Domchek; T. Rebbeck; A. Lasa; I. Konstantopoulou; F. B. Hogervorst; S. Verhoef; M. F. van Dooren; A. Jager; M. G. E. M. Ausems; C. M. Aalfs; C. J. van Asperen; M. Vreeswijk; Q. Waisfisz; C. E. Van Roozendaal; M. J. Ligtenberg; D. F. Easton; S. Peock; M. Cook; C. T. Oliver; D. Frost; B. Curzon; D. G. Evans; F. Lalloo; R. Eeles; L. Izatt; R. Davidson; J. Adlard; D. Eccles; K-R Ong; F. Douglas; S. Downing; C. Brewer; L. Walker; H. Nevanlinna; K. Aittomaki; F. J. Couch; Z. Fredericksen; N. M. Lindor; A. Godwin; C. Isaacs; M. A. Caligo; Niklas Loman; Helena Jernström; G. Barbany-Bustinza; A. Liljegren; Hans Ehrencrona; M. Stenmark-Askmalm; L. Feliubadalo; S. Manoukian; B. Peissel; D. Zaffaroni; B. Bonanni; S. Fortuzzi; O. T. Johannsson; G. Chenevix-Trench; X-C Chen; J. Beesley; A. B. Spurdle; O. M. Sinilnikova; S. Healey; L. McGuffog; A. C. Antoniou; J. Brunet; P. Radice; J. Benitez

doi:10.1038/bjc.2011.91

Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2

A. Osorio, R. L. Milne, R. Alonso, G. Pita, P. Peterlongo, A. Teule, K. L. Nathanson, S. M. Domchek, T. Rebbeck, A. Lasa, I. Konstantopoulou, F. B. Hogervorst, S. Verhoef, M. F. van Dooren, A. Jager, M. G. E. M. Ausems, C. M. Aalfs, C. J. van Asperen, M. Vreeswijk, Q. WaisfiszC. E. Van Roozendaal, M. J. Ligtenberg, D. F. Easton, S. Peock, M. Cook, C. T. Oliver, D. Frost, B. Curzon, D. G. Evans, F. Lalloo, R. Eeles, L. Izatt, R. Davidson, J. Adlard, D. Eccles, K-R Ong, F. Douglas, S. Downing, C. Brewer, L. Walker, H. Nevanlinna, K. Aittomaki, F. J. Couch, Z. Fredericksen, N. M. Lindor, A. Godwin, C. Isaacs, M. A. Caligo, Niklas Loman, Helena Jernström, G. Barbany-Bustinza, A. Liljegren, Hans Ehrencrona, M. Stenmark-Askmalm, L. Feliubadalo, S. Manoukian, B. Peissel, D. Zaffaroni, B. Bonanni, S. Fortuzzi, O. T. Johannsson, G. Chenevix-Trench, X-C Chen, J. Beesley, A. B. Spurdle, O. M. Sinilnikova, S. Healey, L. McGuffog, A. C. Antoniou, J. Brunet, P. Radice, J. Benitez

Breastcancer-genetics

Uppsala University

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. METHODS: Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. RESULTS: An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. CONCLUSIONS AND INTERPRETATION: No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers. British Journal of Cancer (2011) 104, 1356-1361. doi:10.1038/bjc.2011.91 www.bjcancer.com Published online 22 March 2011 (C) 2011 Cancer Research UK

Original language	English
Pages (from-to)	1356-1361
Journal	British Journal of Cancer
Volume	104
Issue number	8
DOIs	https://doi.org/10.1038/bjc.2011.91
Publication status	Published - 2011

Subject classification (UKÄ)

Cancer and Oncology

Free keywords

Genetic Predisposition to Disease
BRCA2
BRCA1
Genes
Focus Groups
Female
Genetic
Epistasis
DNA-Binding Proteins
Carcinoma
Breast Neoplasms
80 and over
Aged
Adolescent
Adult
Heterozygote
Humans
Middle Aged
Phenotype
Polymorphism
Single Nucleotide
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/bjc.2011.91

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Osorio, A., Milne, R. L., Alonso, R., Pita, G., Peterlongo, P., Teule, A., Nathanson, K. L., Domchek, S. M., Rebbeck, T., Lasa, A., Konstantopoulou, I., Hogervorst, F. B., Verhoef, S., van Dooren, M. F., Jager, A., Ausems, M. G. E. M., Aalfs, C. M., van Asperen, C. J., Vreeswijk, M., ... Benitez, J. (2011). Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2. British Journal of Cancer, 104(8), 1356-1361. https://doi.org/10.1038/bjc.2011.91

@article{fd3db35e17d247ed95a6e81cdffe31d1,

title = "Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2",

abstract = "BACKGROUND: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. METHODS: Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. RESULTS: An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. CONCLUSIONS AND INTERPRETATION: No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers. British Journal of Cancer (2011) 104, 1356-1361. doi:10.1038/bjc.2011.91 www.bjcancer.com Published online 22 March 2011 (C) 2011 Cancer Research UK",

keywords = "Genetic Predisposition to Disease, BRCA2, BRCA1, Genes, Focus Groups, Female, Genetic, Epistasis, DNA-Binding Proteins, Carcinoma, Breast Neoplasms, 80 and over, Aged, Adolescent, Adult, Heterozygote, Humans, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Young Adult",

author = "A. Osorio and Milne, {R. L.} and R. Alonso and G. Pita and P. Peterlongo and A. Teule and Nathanson, {K. L.} and Domchek, {S. M.} and T. Rebbeck and A. Lasa and I. Konstantopoulou and Hogervorst, {F. B.} and S. Verhoef and {van Dooren}, {M. F.} and A. Jager and Ausems, {M. G. E. M.} and Aalfs, {C. M.} and {van Asperen}, {C. J.} and M. Vreeswijk and Q. Waisfisz and {Van Roozendaal}, {C. E.} and Ligtenberg, {M. J.} and Easton, {D. F.} and S. Peock and M. Cook and Oliver, {C. T.} and D. Frost and B. Curzon and Evans, {D. G.} and F. Lalloo and R. Eeles and L. Izatt and R. Davidson and J. Adlard and D. Eccles and K-R Ong and F. Douglas and S. Downing and C. Brewer and L. Walker and H. Nevanlinna and K. Aittomaki and Couch, {F. J.} and Z. Fredericksen and Lindor, {N. M.} and A. Godwin and C. Isaacs and Caligo, {M. A.} and Niklas Loman and Helena Jernstr{\"o}m and G. Barbany-Bustinza and A. Liljegren and Hans Ehrencrona and M. Stenmark-Askmalm and L. Feliubadalo and S. Manoukian and B. Peissel and D. Zaffaroni and B. Bonanni and S. Fortuzzi and Johannsson, {O. T.} and G. Chenevix-Trench and X-C Chen and J. Beesley and Spurdle, {A. B.} and Sinilnikova, {O. M.} and S. Healey and L. McGuffog and Antoniou, {A. C.} and J. Brunet and P. Radice and J. Benitez",

year = "2011",

doi = "10.1038/bjc.2011.91",

language = "English",

volume = "104",

pages = "1356--1361",

journal = "British Journal of Cancer",

issn = "1532-1827",

publisher = "Nature Publishing Group",

number = "8",

}

Osorio, A, Milne, RL, Alonso, R, Pita, G, Peterlongo, P, Teule, A, Nathanson, KL, Domchek, SM, Rebbeck, T, Lasa, A, Konstantopoulou, I, Hogervorst, FB, Verhoef, S, van Dooren, MF, Jager, A, Ausems, MGEM, Aalfs, CM, van Asperen, CJ, Vreeswijk, M, Waisfisz, Q, Van Roozendaal, CE, Ligtenberg, MJ, Easton, DF, Peock, S, Cook, M, Oliver, CT, Frost, D, Curzon, B, Evans, DG, Lalloo, F, Eeles, R, Izatt, L, Davidson, R, Adlard, J, Eccles, D, Ong, K-R, Douglas, F, Downing, S, Brewer, C, Walker, L, Nevanlinna, H, Aittomaki, K, Couch, FJ, Fredericksen, Z, Lindor, NM, Godwin, A, Isaacs, C, Caligo, MA, Loman, N , Jernström, H, Barbany-Bustinza, G, Liljegren, A, Ehrencrona, H, Stenmark-Askmalm, M, Feliubadalo, L, Manoukian, S, Peissel, B, Zaffaroni, D, Bonanni, B, Fortuzzi, S, Johannsson, OT, Chenevix-Trench, G, Chen, X-C, Beesley, J, Spurdle, AB, Sinilnikova, OM, Healey, S, McGuffog, L, Antoniou, AC, Brunet, J, Radice, P & Benitez, J 2011, 'Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2', British Journal of Cancer, vol. 104, no. 8, pp. 1356-1361. https://doi.org/10.1038/bjc.2011.91

TY - JOUR

T1 - Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2

AU - Osorio, A.

AU - Milne, R. L.

AU - Alonso, R.

AU - Pita, G.

AU - Peterlongo, P.

AU - Teule, A.

AU - Nathanson, K. L.

AU - Domchek, S. M.

AU - Rebbeck, T.

AU - Lasa, A.

AU - Konstantopoulou, I.

AU - Hogervorst, F. B.

AU - Verhoef, S.

AU - van Dooren, M. F.

AU - Jager, A.

AU - Ausems, M. G. E. M.

AU - Aalfs, C. M.

AU - van Asperen, C. J.

AU - Vreeswijk, M.

AU - Waisfisz, Q.

AU - Van Roozendaal, C. E.

AU - Ligtenberg, M. J.

AU - Easton, D. F.

AU - Peock, S.

AU - Cook, M.

AU - Oliver, C. T.

AU - Frost, D.

AU - Curzon, B.

AU - Evans, D. G.

AU - Lalloo, F.

AU - Eeles, R.

AU - Izatt, L.

AU - Davidson, R.

AU - Adlard, J.

AU - Eccles, D.

AU - Ong, K-R

AU - Douglas, F.

AU - Downing, S.

AU - Brewer, C.

AU - Walker, L.

AU - Nevanlinna, H.

AU - Aittomaki, K.

AU - Couch, F. J.

AU - Fredericksen, Z.

AU - Lindor, N. M.

AU - Godwin, A.

AU - Isaacs, C.

AU - Caligo, M. A.

AU - Loman, Niklas

AU - Jernström, Helena

AU - Barbany-Bustinza, G.

AU - Liljegren, A.

AU - Ehrencrona, Hans

AU - Stenmark-Askmalm, M.

AU - Feliubadalo, L.

AU - Manoukian, S.

AU - Peissel, B.

AU - Zaffaroni, D.

AU - Bonanni, B.

AU - Fortuzzi, S.

AU - Johannsson, O. T.

AU - Chenevix-Trench, G.

AU - Chen, X-C

AU - Beesley, J.

AU - Spurdle, A. B.

AU - Sinilnikova, O. M.

AU - Healey, S.

AU - McGuffog, L.

AU - Antoniou, A. C.

AU - Brunet, J.

AU - Radice, P.

AU - Benitez, J.

PY - 2011

Y1 - 2011

N2 - BACKGROUND: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. METHODS: Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. RESULTS: An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. CONCLUSIONS AND INTERPRETATION: No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers. British Journal of Cancer (2011) 104, 1356-1361. doi:10.1038/bjc.2011.91 www.bjcancer.com Published online 22 March 2011 (C) 2011 Cancer Research UK

AB - BACKGROUND: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. METHODS: Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. RESULTS: An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. CONCLUSIONS AND INTERPRETATION: No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers. British Journal of Cancer (2011) 104, 1356-1361. doi:10.1038/bjc.2011.91 www.bjcancer.com Published online 22 March 2011 (C) 2011 Cancer Research UK

KW - Genetic Predisposition to Disease

KW - BRCA2

KW - BRCA1

KW - Genes

KW - Focus Groups

KW - Female

KW - Genetic

KW - Epistasis

KW - DNA-Binding Proteins

KW - Carcinoma

KW - Breast Neoplasms

KW - 80 and over

KW - Aged

KW - Adolescent

KW - Adult

KW - Heterozygote

KW - Humans

KW - Middle Aged

KW - Phenotype

KW - Polymorphism

KW - Single Nucleotide

KW - Young Adult

U2 - 10.1038/bjc.2011.91

DO - 10.1038/bjc.2011.91

M3 - Article

C2 - 21427728

SN - 1532-1827

VL - 104

SP - 1356

EP - 1361

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 8

ER -

Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2

Abstract

Subject classification (UKÄ)

Free keywords

UN SDGs

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