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

Antonis C. Antoniou; Olga M. Sinilnikova; Lesley McGuffog; Sue Healey; Heli Nevanlinna; Tuomas Heikkinen; Jacques Simard; Amanda B. Spurdle; Jonathan Beesley; Xiaoqing Chen; Susan L. Neuhausen; Yuan C. Ding; Fergus J. Couch; Xianshu Wang; Zachary Fredericksen; Paolo Peterlongo; Bernard Peissel; Bernardo Bonanni; Alessandra Viel; Loris Bernard; Paolo Radice; Csilla I. Szabo; Lenka Foretova; Michal Zikan; Kathleen Claes; Mark H. Greene; Phuong L. Mai; Gad Rennert; Flavio Lejbkowicz; Irene L. Andrulis; Hilmi Ozcelik; Gord Glendon; Anne-Marie Gerdes; Mads Thomassen; Lone Sunde; Maria A. Caligo; Yael Laitman; Tair Kontorovich; Shimrit Cohen; Bella Kaufman; Efrat Dagan; Ruth Gershoni Baruch; Eitan Friedman; Katja Harbst; Gisela Barbany-Bustinza; Johanna Rantala; Hans Ehrencrona; Per Karlsson; Susan M. Domchek; Katherine L. Nathanson; Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab); OCGN; HEBON; EMBRACE; GEMO; Breast Cancer Family Registry (BCFR); CIMBA; Encarna B. Gomez Garcia

doi:10.1093/hmg/ddp372

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

Antonis C. Antoniou^*, Olga M. Sinilnikova, Lesley McGuffog, Sue Healey, Heli Nevanlinna, Tuomas Heikkinen, Jacques Simard, Amanda B. Spurdle, Jonathan Beesley, Xiaoqing Chen, Susan L. Neuhausen, Yuan C. Ding, Fergus J. Couch, Xianshu Wang, Zachary Fredericksen, Paolo Peterlongo, Bernard Peissel, Bernardo Bonanni, Alessandra Viel, Loris BernardPaolo Radice, Csilla I. Szabo, Lenka Foretova, Michal Zikan, Kathleen Claes, Mark H. Greene, Phuong L. Mai, Gad Rennert, Flavio Lejbkowicz, Irene L. Andrulis, Hilmi Ozcelik, Gord Glendon, Anne-Marie Gerdes, Mads Thomassen, Lone Sunde, Maria A. Caligo, Yael Laitman, Tair Kontorovich, Shimrit Cohen, Bella Kaufman, Efrat Dagan, Ruth Gershoni Baruch, Eitan Friedman, Katja Harbst, Gisela Barbany-Bustinza, Johanna Rantala, Hans Ehrencrona, Per Karlsson, Susan M. Domchek, Katherine L. Nathanson, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), OCGN, HEBON, EMBRACE, GEMO, Breast Cancer Family Registry (BCFR), CIMBA, Encarna B. Gomez Garcia

^*Corresponding author for this work

GROW - Research Institute for Oncology and Reproduction

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	English
Pages (from-to)	4442-4456
Number of pages	15
Journal	Human Molecular Genetics
Volume	18
Issue number	22
DOIs	https://doi.org/10.1093/hmg/ddp372
Publication status	Published - 15 Nov 2009

Keywords

Genome-wide association
Estrogen-receptor
Ovarian-cancer
Susceptibility
Gene
Population
Expression
Alleles

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10.1093/hmg/ddp372

Cite this

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. C., Couch, F. J., Wang, X., Fredericksen, Z., Peterlongo, P., Peissel, B., Bonanni, B., Viel, A., ... Gomez Garcia, E. B. (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{03e9c1d2610e43eca3ee6850f7999dd1,

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.",

keywords = "Genome-wide association, Estrogen-receptor, Ovarian-cancer, Susceptibility, Gene, Population, Expression, Alleles",

author = "Antoniou, {Antonis C.} and Sinilnikova, {Olga M.} and Lesley McGuffog and Sue Healey and Heli Nevanlinna and Tuomas Heikkinen and Jacques Simard and Spurdle, {Amanda B.} and Jonathan Beesley and Xiaoqing Chen and Neuhausen, {Susan L.} and Ding, {Yuan C.} and Couch, {Fergus J.} and Xianshu Wang and Zachary Fredericksen and Paolo Peterlongo and Bernard Peissel and Bernardo Bonanni and Alessandra Viel and Loris Bernard and Paolo Radice and Szabo, {Csilla I.} and Lenka Foretova and Michal Zikan and Kathleen Claes and Greene, {Mark H.} and Mai, {Phuong L.} and Gad Rennert and Flavio Lejbkowicz and Andrulis, {Irene L.} and Hilmi Ozcelik and Gord Glendon and Anne-Marie Gerdes and Mads Thomassen and Lone Sunde and Caligo, {Maria A.} and Yael Laitman and Tair Kontorovich and Shimrit Cohen and Bella Kaufman and Efrat Dagan and Baruch, {Ruth Gershoni} and Eitan Friedman and Katja Harbst and Gisela Barbany-Bustinza and Johanna Rantala and Hans Ehrencrona and Per Karlsson and Domchek, {Susan M.} and Nathanson, {Katherine L.} and {Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)} and OCGN and HEBON and EMBRACE and GEMO and {Breast Cancer Family Registry (BCFR)} and CIMBA and {Gomez Garcia}, {Encarna B.}",

year = "2009",

month = nov,

day = "15",

doi = "10.1093/hmg/ddp372",

language = "English",

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, YC, Couch, FJ, Wang, X, Fredericksen, Z, Peterlongo, P, Peissel, B, Bonanni, B, Viel, A, Bernard, L, Radice, P, Szabo, CI, Foretova, L, Zikan, M, Claes, K, Greene, MH, Mai, PL, Rennert, G, Lejbkowicz, F, Andrulis, IL, Ozcelik, H, Glendon, G, Gerdes, A-M, Thomassen, M, Sunde, L, Caligo, MA, Laitman, Y, Kontorovich, T, Cohen, S, Kaufman, B, Dagan, E, Baruch, RG, Friedman, E, Harbst, K, Barbany-Bustinza, G, Rantala, J, Ehrencrona, H, Karlsson, P, Domchek, SM, Nathanson, KL, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), OCGN, HEBON, EMBRACE, GEMO, Breast Cancer Family Registry (BCFR), CIMBA & Gomez Garcia, EB 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, Antonis C.

AU - Sinilnikova, Olga M.

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Nevanlinna, Heli

AU - Heikkinen, Tuomas

AU - Simard, Jacques

AU - Spurdle, Amanda B.

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - Neuhausen, Susan L.

AU - Ding, Yuan C.

AU - Couch, Fergus J.

AU - Wang, Xianshu

AU - Fredericksen, Zachary

AU - Peterlongo, Paolo

AU - Peissel, Bernard

AU - Bonanni, Bernardo

AU - Viel, Alessandra

AU - Bernard, Loris

AU - Radice, Paolo

AU - Szabo, Csilla I.

AU - Foretova, Lenka

AU - Zikan, Michal

AU - Claes, Kathleen

AU - Greene, Mark H.

AU - Mai, Phuong L.

AU - Rennert, Gad

AU - Lejbkowicz, Flavio

AU - Andrulis, Irene L.

AU - Ozcelik, Hilmi

AU - Glendon, Gord

AU - Gerdes, Anne-Marie

AU - Thomassen, Mads

AU - Sunde, Lone

AU - Caligo, Maria A.

AU - Laitman, Yael

AU - Kontorovich, Tair

AU - Cohen, Shimrit

AU - Kaufman, Bella

AU - Dagan, Efrat

AU - Baruch, Ruth Gershoni

AU - Friedman, Eitan

AU - Harbst, Katja

AU - Barbany-Bustinza, Gisela

AU - Rantala, Johanna

AU - Ehrencrona, Hans

AU - Karlsson, Per

AU - Domchek, Susan M.

AU - Nathanson, Katherine L.

AU - Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)

AU - OCGN

AU - HEBON

AU - EMBRACE

AU - GEMO

AU - Breast Cancer Family Registry (BCFR)

AU - CIMBA

AU - Gomez Garcia, Encarna B.

PY - 2009/11/15

Y1 - 2009/11/15

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.

KW - Genome-wide association

KW - Estrogen-receptor

KW - Ovarian-cancer

KW - Susceptibility

KW - Gene

KW - Population

KW - Expression

KW - Alleles

U2 - 10.1093/hmg/ddp372

DO - 10.1093/hmg/ddp372

M3 - Article

C2 - 19656774

SN - 0964-6906

VL - 18

SP - 4442

EP - 4456

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 22

ER -

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

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