Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

A.C. Antoniou; O.M. Sinilnikova; L. McGuffog; S. Healey; H. Nevanlinna; T. Heikkinen; J. Simard; A.B. Spurdle; J. Beesley; X. Chen; S.L. Neuhausen; Y. Ding; F.J. Couch; X. Wang; Z. Fredericksen; P. Peterlongo; B. Peissel; B. Bonanni; A. Viel; L. Bernard; P. Radice; C. Szabo; L. Foretova; M. Zikan; K Claes; M.H. Greene; P.L. Mai; G. Rennert; F. Lejbkowicz; I.L. Andrulis; H. Ozcelik; G. Glendon; A.M. Gerdes; M. Thomassen; L. Sunde; M.A. Caligo; Y. Laitman; T. Kontorovich; S.J. Cohen; B. Kaufman; E. Dagan; R.G. Baruch; E. Friedman; K. Harbst; G. Barbany-Bustinza; J. Rantala; H. Ehrencrona; P.S. Karlsson; S.M. Domchek; K.L. Nathanson; A. Osorio; I. Blanco; A. Lasa; J. Benitez; U. Hamann; FB Hogervorst; M.A. Rookus; J.M. Collee; P. Devilee; M.J.L. Ligtenberg; R. van der Luijt; C.M. Aalfs; Q. Waisfisz; J.G. Wijnen; C.E.P. van Roozendaal; S. Peock; M. Cook; D. Frost; C. Oliver; R. Platte; D. Evans; F. Lalloo; R. Eeles; L. Izatt; R. Davidson; C. Chu; D. Eccles; T. Cole; SV Hodgson; A.K. Godwin; D. Stoppa-Lyonnet; B. Buecher; M. Leone; B. Bressac-de Paillerets; A. Remenieras; O. Caron; G.M. Lenoir; N. Sevenet; M. Longy; S.F. Ferrer; F. Prieur; D. Goldgar; A. Miron; E.M. John; S.G.M. Buys; M. Daly

doi:10.1093/hmg/ddp372

Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

A.C. Antoniou, O.M. Sinilnikova, L. McGuffog, S. Healey, H. Nevanlinna, T. Heikkinen, J. Simard, A.B. Spurdle, J. Beesley, X. Chen, S.L. Neuhausen, Y. Ding, F.J. Couch, X. Wang, Z. Fredericksen, P. Peterlongo, B. Peissel, B. Bonanni, A. Viel, L. BernardP. Radice, C. Szabo, L. Foretova, M. Zikan, K Claes, M.H. Greene, P.L. Mai, G. Rennert, F. Lejbkowicz, I.L. Andrulis, H. Ozcelik, G. Glendon, A.M. Gerdes, M. Thomassen, L. Sunde, M.A. Caligo, Y. Laitman, T. Kontorovich, S.J. Cohen, B. Kaufman, E. Dagan, R.G. Baruch, E. Friedman, K. Harbst, G. Barbany-Bustinza, J. Rantala, H. Ehrencrona, P.S. Karlsson, S.M. Domchek, K.L. Nathanson, A. Osorio, I. Blanco, A. Lasa, J. Benitez, U. Hamann, FB Hogervorst, M.A. Rookus, J.M. Collee, P. Devilee, M.J.L. Ligtenberg, R. van der Luijt, C.M. Aalfs, Q. Waisfisz, J.G. Wijnen, C.E.P. van Roozendaal, S. Peock, M. Cook, D. Frost, C. Oliver, R. Platte, D. Evans, F. Lalloo, R. Eeles, L. Izatt, R. Davidson, C. Chu, D. Eccles, T. Cole, SV Hodgson, A.K. Godwin, D. Stoppa-Lyonnet, B. Buecher, M. Leone, B. Bressac-de Paillerets, A. Remenieras, O. Caron, G.M. Lenoir, N. Sevenet, M. Longy, S.F. Ferrer, F. Prieur, D. Goldgar, A. Miron, E.M. John, S.G.M. Buys, M. Daly

Human genetics

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

Abstract

Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not

Original language	Undefined/Unknown
Pages (from-to)	4442-4456
Journal	Human Molecular Genetics
Volume	18
Issue number	22
DOIs	https://doi.org/10.1093/hmg/ddp372
Publication status	Published - 2009

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10.1093/hmg/ddp372

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Antoniou, A. C., Sinilnikova, O. M., McGuffog, L., Healey, S., Nevanlinna, H., Heikkinen, T., Simard, J., Spurdle, A. B., Beesley, J., Chen, X., Neuhausen, S. L., Ding, Y., Couch, F. J., Wang, X., Fredericksen, Z., Peterlongo, P., Peissel, B., Bonanni, B., Viel, A., ... Daly, M. (2009). Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers. Human Molecular Genetics, 18(22), 4442-4456. https://doi.org/10.1093/hmg/ddp372

@article{a15382feedb44b71ac932d4d823fe920,

title = "Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers",

abstract = "Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not",

author = "A.C. Antoniou and O.M. Sinilnikova and L. McGuffog and S. Healey and H. Nevanlinna and T. Heikkinen and J. Simard and A.B. Spurdle and J. Beesley and X. Chen and S.L. Neuhausen and Y. Ding and F.J. Couch and X. Wang and Z. Fredericksen and P. Peterlongo and B. Peissel and B. Bonanni and A. Viel and L. Bernard and P. Radice and C. Szabo and L. Foretova and M. Zikan and K Claes and M.H. Greene and P.L. Mai and G. Rennert and F. Lejbkowicz and I.L. Andrulis and H. Ozcelik and G. Glendon and A.M. Gerdes and M. Thomassen and L. Sunde and M.A. Caligo and Y. Laitman and T. Kontorovich and S.J. Cohen and B. Kaufman and E. Dagan and R.G. Baruch and E. Friedman and K. Harbst and G. Barbany-Bustinza and J. Rantala and H. Ehrencrona and P.S. Karlsson and S.M. Domchek and K.L. Nathanson and A. Osorio and I. Blanco and A. Lasa and J. Benitez and U. Hamann and FB Hogervorst and M.A. Rookus and J.M. Collee and P. Devilee and M.J.L. Ligtenberg and {van der Luijt}, R. and C.M. Aalfs and Q. Waisfisz and J.G. Wijnen and {van Roozendaal}, C.E.P. and S. Peock and M. Cook and D. Frost and C. Oliver and R. Platte and D. Evans and F. Lalloo and R. Eeles and L. Izatt and R. Davidson and C. Chu and D. Eccles and T. Cole and SV Hodgson and A.K. Godwin and D. Stoppa-Lyonnet and B. Buecher and M. Leone and {Bressac-de Paillerets}, B. and A. Remenieras and O. Caron and G.M. Lenoir and N. Sevenet and M. Longy and S.F. Ferrer and F. Prieur and D. Goldgar and A. Miron and E.M. John and S.G.M. Buys and M. Daly",

year = "2009",

doi = "10.1093/hmg/ddp372",

language = "Undefined/Unknown",

volume = "18",

pages = "4442--4456",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "22",

}

Antoniou, AC, Sinilnikova, OM, McGuffog, L, Healey, S, Nevanlinna, H, Heikkinen, T, Simard, J, Spurdle, AB, Beesley, J, Chen, X, Neuhausen, SL, Ding, Y, Couch, FJ, Wang, X, Fredericksen, Z, Peterlongo, P, Peissel, B, Bonanni, B, Viel, A, Bernard, L, Radice, P, Szabo, C, Foretova, L, Zikan, M, Claes, K, Greene, MH, Mai, PL, Rennert, G, Lejbkowicz, F, Andrulis, IL, Ozcelik, H, Glendon, G, Gerdes, AM, Thomassen, M, Sunde, L, Caligo, MA, Laitman, Y, Kontorovich, T, Cohen, SJ, Kaufman, B, Dagan, E, Baruch, RG, Friedman, E, Harbst, K, Barbany-Bustinza, G, Rantala, J, Ehrencrona, H, Karlsson, PS, Domchek, SM, Nathanson, KL, Osorio, A, Blanco, I, Lasa, A, Benitez, J, Hamann, U, Hogervorst, FB, Rookus, MA, Collee, JM, Devilee, P, Ligtenberg, MJL, van der Luijt, R, Aalfs, CM, Waisfisz, Q, Wijnen, JG, van Roozendaal, CEP, Peock, S, Cook, M, Frost, D, Oliver, C, Platte, R, Evans, D, Lalloo, F, Eeles, R, Izatt, L, Davidson, R, Chu, C, Eccles, D, Cole, T, Hodgson, SV, Godwin, AK, Stoppa-Lyonnet, D, Buecher, B, Leone, M, Bressac-de Paillerets, B, Remenieras, A, Caron, O, Lenoir, GM, Sevenet, N, Longy, M, Ferrer, SF, Prieur, F, Goldgar, D, Miron, A, John, EM, Buys, SGM & Daly, M 2009, 'Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers', Human Molecular Genetics, vol. 18, no. 22, pp. 4442-4456. https://doi.org/10.1093/hmg/ddp372

TY - JOUR

T1 - Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

AU - Antoniou, A.C.

AU - Sinilnikova, O.M.

AU - McGuffog, L.

AU - Healey, S.

AU - Nevanlinna, H.

AU - Heikkinen, T.

AU - Simard, J.

AU - Spurdle, A.B.

AU - Beesley, J.

AU - Chen, X.

AU - Neuhausen, S.L.

AU - Ding, Y.

AU - Couch, F.J.

AU - Wang, X.

AU - Fredericksen, Z.

AU - Peterlongo, P.

AU - Peissel, B.

AU - Bonanni, B.

AU - Viel, A.

AU - Bernard, L.

AU - Radice, P.

AU - Szabo, C.

AU - Foretova, L.

AU - Zikan, M.

AU - Claes, K

AU - Greene, M.H.

AU - Mai, P.L.

AU - Rennert, G.

AU - Lejbkowicz, F.

AU - Andrulis, I.L.

AU - Ozcelik, H.

AU - Glendon, G.

AU - Gerdes, A.M.

AU - Thomassen, M.

AU - Sunde, L.

AU - Caligo, M.A.

AU - Laitman, Y.

AU - Kontorovich, T.

AU - Cohen, S.J.

AU - Kaufman, B.

AU - Dagan, E.

AU - Baruch, R.G.

AU - Friedman, E.

AU - Harbst, K.

AU - Barbany-Bustinza, G.

AU - Rantala, J.

AU - Ehrencrona, H.

AU - Karlsson, P.S.

AU - Domchek, S.M.

AU - Nathanson, K.L.

AU - Osorio, A.

AU - Blanco, I.

AU - Lasa, A.

AU - Benitez, J.

AU - Hamann, U.

AU - Hogervorst, FB

AU - Rookus, M.A.

AU - Collee, J.M.

AU - Devilee, P.

AU - Ligtenberg, M.J.L.

AU - van der Luijt, R.

AU - Aalfs, C.M.

AU - Waisfisz, Q.

AU - Wijnen, J.G.

AU - van Roozendaal, C.E.P.

AU - Peock, S.

AU - Cook, M.

AU - Frost, D.

AU - Oliver, C.

AU - Platte, R.

AU - Evans, D.

AU - Lalloo, F.

AU - Eeles, R.

AU - Izatt, L.

AU - Davidson, R.

AU - Chu, C.

AU - Eccles, D.

AU - Cole, T.

AU - Hodgson, SV

AU - Godwin, A.K.

AU - Stoppa-Lyonnet, D.

AU - Buecher, B.

AU - Leone, M.

AU - Bressac-de Paillerets, B.

AU - Remenieras, A.

AU - Caron, O.

AU - Lenoir, G.M.

AU - Sevenet, N.

AU - Longy, M.

AU - Ferrer, S.F.

AU - Prieur, F.

AU - Goldgar, D.

AU - Miron, A.

AU - John, E.M.

AU - Buys, S.G.M.

AU - Daly, M.

PY - 2009

Y1 - 2009

N2 - Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not

AB - Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not

U2 - 10.1093/hmg/ddp372

DO - 10.1093/hmg/ddp372

M3 - Article

C2 - 19656774

VL - 18

SP - 4442

EP - 4456

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 22

ER -