Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Antonis C Antoniou; Karoline B Kuchenbaecker; Penny Soucy; Jonathan Beesley; Xiaoqing Chen; Lesley McGuffog; Andrew Roger Lee; Daniel Barrowdale; Sue Healey; Olga M Sinilnikova; Maria A Caligo; Niklas Loman; Katja Harbst; Annika Lindblom; Brita Arver; Richard Rosenquist; Per W. Karlsson; Kate Nathanson; Susan Domchek; Tim Rebbeck; Anna Jakubowska; Jan Lubinski; Katarzyna Jaworska; Katarzyna Durda; Elżbieta Złowowcka-Perłowska; Ana Osorio; Mercedes Durán; Raquel Andrés; Javier Benítez; Ute Hamann; Frans B Hogervorst; Theo A van Os; Senno Verhoef; Hanne E J Meijers-Heijboer; Juul Wijnen; Encarna B Gómez Garcia; Marjolijn J Ligtenberg; Mieke Kriege; J Margriet Collée; Margreet G E M Ausems; Jan C Oosterwijk; Susan Peock; Debra Frost; Steve D Ellis; Radka Platte; Elena Fineberg; D Gareth Evans; Fiona Lalloo; Finn C Nielsen; Anne-Marie Gerdes; CIMBA, SWE-BRCA

doi:10.1186/bcr3121

Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Antonis C Antoniou, Karoline B Kuchenbaecker, Penny Soucy, Jonathan Beesley, Xiaoqing Chen, Lesley McGuffog, Andrew Roger Lee, Daniel Barrowdale, Sue Healey, Olga M Sinilnikova, Maria A Caligo, Niklas Loman, Katja Harbst, Annika Lindblom, Brita Arver, Richard Rosenquist, Per W. Karlsson, Kate Nathanson, Susan Domchek, Tim RebbeckAnna Jakubowska, Jan Lubinski, Katarzyna Jaworska, Katarzyna Durda, Elżbieta Złowowcka-Perłowska, Ana Osorio, Mercedes Durán, Raquel Andrés, Javier Benítez, Ute Hamann, Frans B Hogervorst, Theo A van Os, Senno Verhoef, Hanne E J Meijers-Heijboer, Juul Wijnen, Encarna B Gómez Garcia, Marjolijn J Ligtenberg, Mieke Kriege, J Margriet Collée, Margreet G E M Ausems, Jan C Oosterwijk, Susan Peock, Debra Frost, Steve D Ellis, Radka Platte, Elena Fineberg, D Gareth Evans, Fiona Lalloo, Finn C Nielsen, Anne-Marie Gerdes, CIMBA, SWE-BRCA

65 Citations (Scopus)

Abstract

Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2).Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework.Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10^-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10^-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10^-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049).Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.

Original language	English
Journal	Breast Cancer Research (Online Edition)
Volume	14
Issue number	1
Pages (from-to)	R33
ISSN	1465-5411
DOIs	https://doi.org/10.1186/bcr3121
Publication status	Published - 20 Feb 2012

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Antoniou, A. C., Kuchenbaecker, K. B., Soucy, P., Beesley, J., Chen, X., McGuffog, L., Lee, A. R., Barrowdale, D., Healey, S., Sinilnikova, O. M., Caligo, M. A., Loman, N., Harbst, K., Lindblom, A., Arver, B., Rosenquist, R., Karlsson, P. W., Nathanson, K., Domchek, S., ... CIMBA, SWE-BRCA (2012). Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. Breast Cancer Research (Online Edition), 14(1), R33. https://doi.org/10.1186/bcr3121

Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. / Antoniou, Antonis C; Kuchenbaecker, Karoline B; Soucy, Penny et al.

In: Breast Cancer Research (Online Edition), Vol. 14, No. 1, 20.02.2012, p. R33.

Research output: Contribution to journal › Journal article › Research › peer-review

Antoniou, AC, Kuchenbaecker, KB, Soucy, P, Beesley, J, Chen, X, McGuffog, L, Lee, AR, Barrowdale, D, Healey, S, Sinilnikova, OM, Caligo, MA, Loman, N, Harbst, K, Lindblom, A, Arver, B, Rosenquist, R, Karlsson, PW, Nathanson, K, Domchek, S, Rebbeck, T, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Złowowcka-Perłowska, E, Osorio, A, Durán, M, Andrés, R, Benítez, J, Hamann, U, Hogervorst, FB, van Os, TA, Verhoef, S, Meijers-Heijboer, HEJ, Wijnen, J, Gómez Garcia, EB, Ligtenberg, MJ, Kriege, M, Collée, JM, Ausems, MGEM, Oosterwijk, JC, Peock, S, Frost, D, Ellis, SD, Platte, R, Fineberg, E, Evans, DG, Lalloo, F, Nielsen, FC , Gerdes, A-M & CIMBA, SWE-BRCA 2012, 'Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers', Breast Cancer Research (Online Edition), vol. 14, no. 1, pp. R33. https://doi.org/10.1186/bcr3121

@article{0b947150ac854900ba9439ac29a7126c,

title = "Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers",

abstract = "Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2).Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework.Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049).Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.",

author = "Antoniou, {Antonis C} and Kuchenbaecker, {Karoline B} and Penny Soucy and Jonathan Beesley and Xiaoqing Chen and Lesley McGuffog and Lee, {Andrew Roger} and Daniel Barrowdale and Sue Healey and Sinilnikova, {Olga M} and Caligo, {Maria A} and Niklas Loman and Katja Harbst and Annika Lindblom and Brita Arver and Richard Rosenquist and Karlsson, {Per W.} and Kate Nathanson and Susan Domchek and Tim Rebbeck and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska and Katarzyna Durda and El{\.z}bieta Z{\l}owowcka-Per{\l}owska and Ana Osorio and Mercedes Dur{\'a}n and Raquel Andr{\'e}s and Javier Ben{\'i}tez and Ute Hamann and Hogervorst, {Frans B} and {van Os}, {Theo A} and Senno Verhoef and Meijers-Heijboer, {Hanne E J} and Juul Wijnen and {G{\'o}mez Garcia}, {Encarna B} and Ligtenberg, {Marjolijn J} and Mieke Kriege and Coll{\'e}e, {J Margriet} and Ausems, {Margreet G E M} and Oosterwijk, {Jan C} and Susan Peock and Debra Frost and Ellis, {Steve D} and Radka Platte and Elena Fineberg and Evans, {D Gareth} and Fiona Lalloo and Nielsen, {Finn C} and Anne-Marie Gerdes and Nielsen, {Finn Cilius}",

year = "2012",

month = feb,

day = "20",

doi = "10.1186/bcr3121",

language = "English",

volume = "14",

pages = "R33",

journal = "Breast Cancer Research",

issn = "1465-5411",

publisher = "BioMed Central Ltd.",

number = "1",

}

TY - JOUR

T1 - Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

AU - Antoniou, Antonis C

AU - Kuchenbaecker, Karoline B

AU - Soucy, Penny

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - McGuffog, Lesley

AU - Lee, Andrew Roger

AU - Barrowdale, Daniel

AU - Healey, Sue

AU - Sinilnikova, Olga M

AU - Caligo, Maria A

AU - Loman, Niklas

AU - Harbst, Katja

AU - Lindblom, Annika

AU - Arver, Brita

AU - Rosenquist, Richard

AU - Karlsson, Per W.

AU - Nathanson, Kate

AU - Domchek, Susan

AU - Rebbeck, Tim

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Jaworska, Katarzyna

AU - Durda, Katarzyna

AU - Złowowcka-Perłowska, Elżbieta

AU - Osorio, Ana

AU - Durán, Mercedes

AU - Andrés, Raquel

AU - Benítez, Javier

AU - Hamann, Ute

AU - Hogervorst, Frans B

AU - van Os, Theo A

AU - Verhoef, Senno

AU - Meijers-Heijboer, Hanne E J

AU - Wijnen, Juul

AU - Gómez Garcia, Encarna B

AU - Ligtenberg, Marjolijn J

AU - Kriege, Mieke

AU - Collée, J Margriet

AU - Ausems, Margreet G E M

AU - Oosterwijk, Jan C

AU - Peock, Susan

AU - Frost, Debra

AU - Ellis, Steve D

AU - Platte, Radka

AU - Fineberg, Elena

AU - Evans, D Gareth

AU - Lalloo, Fiona

AU - Nielsen, Finn C

AU - Gerdes, Anne-Marie

AU - CIMBA, SWE-BRCA

PY - 2012/2/20

Y1 - 2012/2/20

N2 - Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2).Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework.Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049).Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.

AB - Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2).Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework.Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049).Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.

U2 - 10.1186/bcr3121

DO - 10.1186/bcr3121

M3 - Journal article

C2 - 22348646

SN - 1465-5411

VL - 14

SP - R33

JO - Breast Cancer Research

JF - Breast Cancer Research

IS - 1

ER -

Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

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