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

AC Antoniou; KB Kuchenbaecker; P Soucy; J Beesley; XQ Chen; L McGuffog; A Lee; D Barrowdale; S Healey; OM Sinilnikova; MA Caligo; N Loman; K Harbst; A Lindblom; B Arver; R Rosenquist; P Karlsson; K Nathanson; S Domchek; T Rebbeck; A Jakubowska; J Lubinski; K Jaworska; K Durda; E Zlowowcka-Perlowska; A Osorio; M (Mercedes) Duran; R Andres; J Benitez; U Hamann; FB Hogervorst; TA van Os; S Verhoef; HEJ Meijers-Heijboer; J (Juul) van Wijnen; EBG Garcia; MJ Ligtenberg; Mieke Kriege; M Collee; MGEM Ausems; JC Oosterwijk; S Peock; D Frost; SD Ellis; R Platte; E Fineberg; DG Evans; F Lalloo; C Jacobs; R Eeles; J Adlard; R Davidson; T Cole; J Cook; J Paterson; F Douglas; C Brewer; S Hodgson; PJ Morrison; L Walker; MT Rogers; A Donaldson; H Dorkins; AK Godwin; B Bove; D Stoppa-Lyonnet; C Houdayer; B Buecher; A de Pauw; S Mazoyer; A Calender; M Leone; B Bressac-de Paillerets; O (Olivier) Caron; H Sobol; M Frenay; F Prieur; SF Ferrer; I Mortemousque; S Buys; M Daly; A Miron; MB Terry; JL Hopper; EM John; M Southey; D Goldgar; CF Singer; A Fink-Retter; MK Tea; DG Kaulich; TVO Hansen; FC Nielsen; RB Barkardottir; M Gaudet; T Kirchhoff; V Joseph; A Dutra-Clarke; K Offit; M Piedmonte; J Kirk; D Cohn; J Hurteau; J Byron; J Fiorica; AE Toland; M Montagna; C Oliani; E Imyanitov; C Isaacs; L Tihomirova; I Blanco; C (Conxi) Lazaro; A Teule; J Del Valle; SA Gayther; K Odunsi; J Gross; BY Karlan; E Olah; SH Teo; PA Ganz; MS Beattie; CM Dorfling; EJ van Rensburg; O Diez; A Kwong; RK Schmutzler; B Wappenschmidt; C Engel; A Meindl; N Ditsch; N Arnold; S Heidemann; D Niederacher; S Preisler-Adams; D Gadzicki; R Varon-Mateeva; H Deissler; A Gehrig; C Sutter; K Kast; B Fiebig; D Schafer; T Caldes; M de la Hoya; H Nevanlinna; TA Muranen; B Lesperance; AB Spurdle; SL Neuhausen; YC Ding; XS Wang; Z Fredericksen; VS Pankratz; NM Lindor; P Peterlongo; S Manoukian; B Peissel; D Zaffaroni; B Bonanni; L Bernard; R Dolcetti; L Papi; L Ottini; P Radice; MH Greene; JT Loud; IL Andrulis; H Ozcelik; AM Mulligan; G Glendon; Marga Thomassen; AM Gerdes; UB Jensen; AB Skytte; TA Kruse; G Chenevix-Trench; FJ Couch; J Simard; DF Easton

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

AC Antoniou, KB Kuchenbaecker, P Soucy, J Beesley, XQ Chen, L McGuffog, A Lee, D Barrowdale, S Healey, OM Sinilnikova, MA Caligo, N Loman, K Harbst, A Lindblom, B Arver, R Rosenquist, P Karlsson, K Nathanson, S Domchek, T RebbeckA Jakubowska, J Lubinski, K Jaworska, K Durda, E Zlowowcka-Perlowska, A Osorio, M (Mercedes) Duran, R Andres, J Benitez, U Hamann, FB Hogervorst, TA van Os, S Verhoef, HEJ Meijers-Heijboer, J (Juul) van Wijnen, EBG Garcia, MJ Ligtenberg, Mieke Kriege, M Collee, MGEM Ausems, JC Oosterwijk, S Peock, D Frost, SD Ellis, R Platte, E Fineberg, DG Evans, F Lalloo, C Jacobs, R Eeles, J Adlard, R Davidson, T Cole, J Cook, J Paterson, F Douglas, C Brewer, S Hodgson, PJ Morrison, L Walker, MT Rogers, A Donaldson, H Dorkins, AK Godwin, B Bove, D Stoppa-Lyonnet, C Houdayer, B Buecher, A de Pauw, S Mazoyer, A Calender, M Leone, B Bressac-de Paillerets, O (Olivier) Caron, H Sobol, M Frenay, F Prieur, SF Ferrer, I Mortemousque, S Buys, M Daly, A Miron, MB Terry, JL Hopper, EM John, M Southey, D Goldgar, CF Singer, A Fink-Retter, MK Tea, DG Kaulich, TVO Hansen, FC Nielsen, RB Barkardottir, M Gaudet, T Kirchhoff, V Joseph, A Dutra-Clarke, K Offit, M Piedmonte, J Kirk, D Cohn, J Hurteau, J Byron, J Fiorica, AE Toland, M Montagna, C Oliani, E Imyanitov, C Isaacs, L Tihomirova, I Blanco, C (Conxi) Lazaro, A Teule, J Del Valle, SA Gayther, K Odunsi, J Gross, BY Karlan, E Olah, SH Teo, PA Ganz, MS Beattie, CM Dorfling, EJ van Rensburg, O Diez, A Kwong, RK Schmutzler, B Wappenschmidt, C Engel, A Meindl, N Ditsch, N Arnold, S Heidemann, D Niederacher, S Preisler-Adams, D Gadzicki, R Varon-Mateeva, H Deissler, A Gehrig, C Sutter, K Kast, B Fiebig, D Schafer, T Caldes, M de la Hoya, H Nevanlinna, TA Muranen, B Lesperance, AB Spurdle, SL Neuhausen, YC Ding, XS Wang, Z Fredericksen, VS Pankratz, NM Lindor, P Peterlongo, S Manoukian, B Peissel, D Zaffaroni, B Bonanni, L Bernard, R Dolcetti, L Papi, L Ottini, P Radice, MH Greene, JT Loud, IL Andrulis, H Ozcelik, AM Mulligan, G Glendon, Marga Thomassen, AM Gerdes, UB Jensen, AB Skytte, TA Kruse, G Chenevix-Trench, FJ Couch, J Simard, DF Easton

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

76 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 x 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 x 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, 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	Undefined/Unknown
Journal	Breast Cancer Research
Volume	14
Issue number	1
DOIs	https://doi.org/10.1186/bcr3121
Publication status	Published - 2012

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Cite this

Antoniou, AC., Kuchenbaecker, KB., Soucy, P., Beesley, J., Chen, XQ., McGuffog, L., Lee, A., Barrowdale, D., Healey, S., Sinilnikova, OM., Caligo, MA., Loman, N., Harbst, K., Lindblom, A., Arver, B., Rosenquist, R., Karlsson, P., Nathanson, K., Domchek, S., ... Easton, DF. (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, 14(1). https://doi.org/10.1186/bcr3121

@article{9e74ea280cbc4f2b879ac0d33676cc48,

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 x 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 x 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, 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 = "AC Antoniou and KB Kuchenbaecker and P Soucy and J Beesley and XQ Chen and L McGuffog and A Lee and D Barrowdale and S Healey and OM Sinilnikova and MA Caligo and N Loman and K Harbst and A Lindblom and B Arver and R Rosenquist and P Karlsson and K Nathanson and S Domchek and T Rebbeck and A Jakubowska and J Lubinski and K Jaworska and K Durda and E Zlowowcka-Perlowska and A Osorio and Duran, {M (Mercedes)} and R Andres and J Benitez and U Hamann and FB Hogervorst and {van Os}, TA and S Verhoef and HEJ Meijers-Heijboer and {van Wijnen}, {J (Juul)} and EBG Garcia and MJ Ligtenberg and Mieke Kriege and M Collee and MGEM Ausems and JC Oosterwijk and S Peock and D Frost and SD Ellis and R Platte and E Fineberg and DG Evans and F Lalloo and C Jacobs and R Eeles and J Adlard and R Davidson and T Cole and J Cook and J Paterson and F Douglas and C Brewer and S Hodgson and PJ Morrison and L Walker and MT Rogers and A Donaldson and H Dorkins and AK Godwin and B Bove and D Stoppa-Lyonnet and C Houdayer and B Buecher and {de Pauw}, A and S Mazoyer and A Calender and M Leone and {Bressac-de Paillerets}, B and Caron, {O (Olivier)} and H Sobol and M Frenay and F Prieur and SF Ferrer and I Mortemousque and S Buys and M Daly and A Miron and MB Terry and JL Hopper and EM John and M Southey and D Goldgar and CF Singer and A Fink-Retter and MK Tea and DG Kaulich and TVO Hansen and FC Nielsen and RB Barkardottir and M Gaudet and T Kirchhoff and V Joseph and A Dutra-Clarke and K Offit and M Piedmonte and J Kirk and D Cohn and J Hurteau and J Byron and J Fiorica and AE Toland and M Montagna and C Oliani and E Imyanitov and C Isaacs and L Tihomirova and I Blanco and Lazaro, {C (Conxi)} and A Teule and {Del Valle}, J and SA Gayther and K Odunsi and J Gross and BY Karlan and E Olah and SH Teo and PA Ganz and MS Beattie and CM Dorfling and {van Rensburg}, EJ and O Diez and A Kwong and RK Schmutzler and B Wappenschmidt and C Engel and A Meindl and N Ditsch and N Arnold and S Heidemann and D Niederacher and S Preisler-Adams and D Gadzicki and R Varon-Mateeva and H Deissler and A Gehrig and C Sutter and K Kast and B Fiebig and D Schafer and T Caldes and {de la Hoya}, M and H Nevanlinna and TA Muranen and B Lesperance and AB Spurdle and SL Neuhausen and YC Ding and XS Wang and Z Fredericksen and VS Pankratz and NM Lindor and P Peterlongo and S Manoukian and B Peissel and D Zaffaroni and B Bonanni and L Bernard and R Dolcetti and L Papi and L Ottini and P Radice and MH Greene and JT Loud and IL Andrulis and H Ozcelik and AM Mulligan and G Glendon and Marga Thomassen and AM Gerdes and UB Jensen and AB Skytte and TA Kruse and G Chenevix-Trench and FJ Couch and J Simard and DF Easton",

year = "2012",

doi = "10.1186/bcr3121",

language = "Undefined/Unknown",

volume = "14",

journal = "Breast Cancer Research",

issn = "1465-5411",

publisher = "BioMed Central Ltd.",

number = "1",

}

Antoniou, AC, Kuchenbaecker, KB, Soucy, P, Beesley, J, Chen, XQ, McGuffog, L, Lee, A, Barrowdale, D, Healey, S, Sinilnikova, OM, Caligo, MA, Loman, N, Harbst, K, Lindblom, A, Arver, B, Rosenquist, R, Karlsson, P, Nathanson, K, Domchek, S, Rebbeck, T, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Zlowowcka-Perlowska, E, Osorio, A, Duran, M, Andres, R, Benitez, J, Hamann, U, Hogervorst, FB, van Os, TA, Verhoef, S, Meijers-Heijboer, HEJ, van Wijnen, J, Garcia, EBG, Ligtenberg, MJ, Kriege, M, Collee, M, Ausems, MGEM, Oosterwijk, JC, Peock, S, Frost, D, Ellis, SD, Platte, R, Fineberg, E, Evans, DG, Lalloo, F, Jacobs, C, Eeles, R, Adlard, J, Davidson, R, Cole, T, Cook, J, Paterson, J, Douglas, F, Brewer, C, Hodgson, S, Morrison, PJ, Walker, L, Rogers, MT, Donaldson, A, Dorkins, H, Godwin, AK, Bove, B, Stoppa-Lyonnet, D, Houdayer, C, Buecher, B, de Pauw, A, Mazoyer, S, Calender, A, Leone, M, Bressac-de Paillerets, B, Caron, O, Sobol, H, Frenay, M, Prieur, F, Ferrer, SF, Mortemousque, I, Buys, S, Daly, M, Miron, A, Terry, MB, Hopper, JL, John, EM, Southey, M, Goldgar, D, Singer, CF, Fink-Retter, A, Tea, MK, Kaulich, DG, Hansen, TVO, Nielsen, FC, Barkardottir, RB, Gaudet, M, Kirchhoff, T, Joseph, V, Dutra-Clarke, A, Offit, K, Piedmonte, M, Kirk, J, Cohn, D, Hurteau, J, Byron, J, Fiorica, J, Toland, AE, Montagna, M, Oliani, C, Imyanitov, E, Isaacs, C, Tihomirova, L, Blanco, I, Lazaro, C, Teule, A, Del Valle, J, Gayther, SA, Odunsi, K, Gross, J, Karlan, BY, Olah, E, Teo, SH, Ganz, PA, Beattie, MS, Dorfling, CM, van Rensburg, EJ, Diez, O, Kwong, A, Schmutzler, RK, Wappenschmidt, B, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Heidemann, S, Niederacher, D, Preisler-Adams, S, Gadzicki, D, Varon-Mateeva, R, Deissler, H, Gehrig, A, Sutter, C, Kast, K, Fiebig, B, Schafer, D, Caldes, T, de la Hoya, M, Nevanlinna, H, Muranen, TA, Lesperance, B, Spurdle, AB, Neuhausen, SL, Ding, YC, Wang, XS, Fredericksen, Z, Pankratz, VS, Lindor, NM, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Bonanni, B, Bernard, L, Dolcetti, R, Papi, L, Ottini, L, Radice, P, Greene, MH, Loud, JT, Andrulis, IL, Ozcelik, H, Mulligan, AM, Glendon, G, Thomassen, M, Gerdes, AM, Jensen, UB, Skytte, AB, Kruse, TA, Chenevix-Trench, G, Couch, FJ, Simard, J & Easton, DF 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, vol. 14, no. 1. https://doi.org/10.1186/bcr3121

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, AC

AU - Kuchenbaecker, KB

AU - Soucy, P

AU - Beesley, J

AU - Chen, XQ

AU - McGuffog, L

AU - Lee, A

AU - Barrowdale, D

AU - Healey, S

AU - Sinilnikova, OM

AU - Caligo, MA

AU - Loman, N

AU - Harbst, K

AU - Lindblom, A

AU - Arver, B

AU - Rosenquist, R

AU - Karlsson, P

AU - Nathanson, K

AU - Domchek, S

AU - Rebbeck, T

AU - Jakubowska, A

AU - Lubinski, J

AU - Jaworska, K

AU - Durda, K

AU - Zlowowcka-Perlowska, E

AU - Osorio, A

AU - Duran, M (Mercedes)

AU - Andres, R

AU - Benitez, J

AU - Hamann, U

AU - Hogervorst, FB

AU - van Os, TA

AU - Verhoef, S

AU - Meijers-Heijboer, HEJ

AU - van Wijnen, J (Juul)

AU - Garcia, EBG

AU - Ligtenberg, MJ

AU - Kriege, Mieke

AU - Collee, M

AU - Ausems, MGEM

AU - Oosterwijk, JC

AU - Peock, S

AU - Frost, D

AU - Ellis, SD

AU - Platte, R

AU - Fineberg, E

AU - Evans, DG

AU - Lalloo, F

AU - Jacobs, C

AU - Eeles, R

AU - Adlard, J

AU - Davidson, R

AU - Cole, T

AU - Cook, J

AU - Paterson, J

AU - Douglas, F

AU - Brewer, C

AU - Hodgson, S

AU - Morrison, PJ

AU - Walker, L

AU - Rogers, MT

AU - Donaldson, A

AU - Dorkins, H

AU - Godwin, AK

AU - Bove, B

AU - Stoppa-Lyonnet, D

AU - Houdayer, C

AU - Buecher, B

AU - de Pauw, A

AU - Mazoyer, S

AU - Calender, A

AU - Leone, M

AU - Bressac-de Paillerets, B

AU - Caron, O (Olivier)

AU - Sobol, H

AU - Frenay, M

AU - Prieur, F

AU - Ferrer, SF

AU - Mortemousque, I

AU - Buys, S

AU - Daly, M

AU - Miron, A

AU - Terry, MB

AU - Hopper, JL

AU - John, EM

AU - Southey, M

AU - Goldgar, D

AU - Singer, CF

AU - Fink-Retter, A

AU - Tea, MK

AU - Kaulich, DG

AU - Hansen, TVO

AU - Nielsen, FC

AU - Barkardottir, RB

AU - Gaudet, M

AU - Kirchhoff, T

AU - Joseph, V

AU - Dutra-Clarke, A

AU - Offit, K

AU - Piedmonte, M

AU - Kirk, J

AU - Cohn, D

AU - Hurteau, J

AU - Byron, J

AU - Fiorica, J

AU - Toland, AE

AU - Montagna, M

AU - Oliani, C

AU - Imyanitov, E

AU - Isaacs, C

AU - Tihomirova, L

AU - Blanco, I

AU - Lazaro, C (Conxi)

AU - Teule, A

AU - Del Valle, J

AU - Gayther, SA

AU - Odunsi, K

AU - Gross, J

AU - Karlan, BY

AU - Olah, E

AU - Teo, SH

AU - Ganz, PA

AU - Beattie, MS

AU - Dorfling, CM

AU - van Rensburg, EJ

AU - Diez, O

AU - Kwong, A

AU - Schmutzler, RK

AU - Wappenschmidt, B

AU - Engel, C

AU - Meindl, A

AU - Ditsch, N

AU - Arnold, N

AU - Heidemann, S

AU - Niederacher, D

AU - Preisler-Adams, S

AU - Gadzicki, D

AU - Varon-Mateeva, R

AU - Deissler, H

AU - Gehrig, A

AU - Sutter, C

AU - Kast, K

AU - Fiebig, B

AU - Schafer, D

AU - Caldes, T

AU - de la Hoya, M

AU - Nevanlinna, H

AU - Muranen, TA

AU - Lesperance, B

AU - Spurdle, AB

AU - Neuhausen, SL

AU - Ding, YC

AU - Wang, XS

AU - Fredericksen, Z

AU - Pankratz, VS

AU - Lindor, NM

AU - Peterlongo, P

AU - Manoukian, S

AU - Peissel, B

AU - Zaffaroni, D

AU - Bonanni, B

AU - Bernard, L

AU - Dolcetti, R

AU - Papi, L

AU - Ottini, L

AU - Radice, P

AU - Greene, MH

AU - Loud, JT

AU - Andrulis, IL

AU - Ozcelik, H

AU - Mulligan, AM

AU - Glendon, G

AU - Thomassen, Marga

AU - Gerdes, AM

AU - Jensen, UB

AU - Skytte, AB

AU - Kruse, TA

AU - Chenevix-Trench, G

AU - Couch, FJ

AU - Simard, J

AU - Easton, DF

PY - 2012

Y1 - 2012

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 x 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 x 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, 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 x 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 x 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, 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 - Article

C2 - 22348646

SN - 1465-5411

VL - 14

JO - Breast Cancer Research

JF - Breast Cancer Research

IS - 1

ER -