Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

FJ Couch; MM Gaudet; AC Antoniou; SJ Ramus; KB Kuchenbaecker; P Soucy; J Beesley; XQ Chen; XS Wang; T Kirchhoff; L McGuffog; D Barrowdale; A Lee; S Healey; OM Sinilnikova; IL Andrulis; H Ozcelik; AM Mulligan; Marga Thomassen; AM Gerdes; UB Jensen; AB Skytte; TA Kruse; MA Caligo; A von Wachenfeldt; G Barbany-Bustinza; N Loman; M Soller; H Ehrencrona; P Karlsson; KL Nathanson; TR Rebbeck; SM Domchek; A Jakubowska; J Lubinski; K Jaworska; K Durda; E Zlowocka; T Huzarski; T Byrski; J Gronwald; C Cybulski; B Gorski; A Osorio; M (Mercedes) Duran; MI Tejada; J Benitez; U Hamann; FBL Hogervorst; TA van Os; FE van Leeuwen; HEJ Meijers-Heijboer; J (Juul) van Wijnen; MJ Blok; M Kets; Maartje Hooning; Rogier Oldenburg; MGEM Ausems; S Peock; D Frost; SD Ellis; R Platte; E Fineberg; DG Evans; C Jacobs; RA Eeles; J Adlard; R Davidson; DM Eccles; T Cole; J Cook; J Paterson; C Brewer; F Douglas; SV Hodgson; PJ Morrison; L Walker; ME Porteous; MJ Kennedy; LE Side; B Bove; AK Godwin; D Stoppa-Lyonnet; M Fassy-Colcombet; L Castera; F Cornelis; S Mazoyer; M Leone; N Boutry-Kryza; B Bressac-de Paillerets; O (Olivier) Caron; P Pujol; I Coupier; C Delnatte; L Akloul; HT Lynch; CL Snyder; SS Buys; MB Daly; M Terry; WK Chung; EM John; A Miron; MC Southey; JL Hopper; DE Goldgar; CF Singer; C Rappaport; MKM Tea; A Fink-Retter; TVO Hansen; FC Nielsen; A Arason; J Vijai; S Shah; K Sarrel; ME Robson; M Piedmonte; K Phillips; J Basil; WS Rubinstein; J Boggess; K Wakeley; A Ewart-Toland; M Montagna; S Agata; EN Imyanitov; C Isaacs; R Janavicius; C (Conxi) Lazaro; I Blanco; L Feliubadalo; J Brunet; SA Gayther; PPD Pharoah; KO Odunsi; BY Karlan; CS Walsh; E Olah; SH Teo; PA Ganz; MS Beattie; EJ van Rensburg; CM Dorfling; 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; W Heinritz; T Caldes; M de la Hoya; TA Muranen; H Nevanlinna; M Tischkowitz; AB Spurdle; SL Neuhausen; YC Ding; NM Lindor; Z Fredericksen; VS Pankratz; P Peterlongo; S Manoukian; B Peissel; D Zaffaroni; M Barile; L Bernard; A Viel; G Giannini; L Varesco; P Radice; MH Greene; PL Mai; DF Easton; G Chenevix-Trench; K Offit; J Simard

doi:10.1158/1055-9965.EPI-11-0888

Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

FJ Couch, MM Gaudet, AC Antoniou, SJ Ramus, KB Kuchenbaecker, P Soucy, J Beesley, XQ Chen, XS Wang, T Kirchhoff, L McGuffog, D Barrowdale, A Lee, S Healey, OM Sinilnikova, IL Andrulis, H Ozcelik, AM Mulligan, Marga Thomassen, AM GerdesUB Jensen, AB Skytte, TA Kruse, MA Caligo, A von Wachenfeldt, G Barbany-Bustinza, N Loman, M Soller, H Ehrencrona, P Karlsson, KL Nathanson, TR Rebbeck, SM Domchek, A Jakubowska, J Lubinski, K Jaworska, K Durda, E Zlowocka, T Huzarski, T Byrski, J Gronwald, C Cybulski, B Gorski, A Osorio, M (Mercedes) Duran, MI Tejada, J Benitez, U Hamann, FBL Hogervorst, TA van Os, FE van Leeuwen, HEJ Meijers-Heijboer, J (Juul) van Wijnen, MJ Blok, M Kets, Maartje Hooning, Rogier Oldenburg, MGEM Ausems, S Peock, D Frost, SD Ellis, R Platte, E Fineberg, DG Evans, C Jacobs, RA Eeles, J Adlard, R Davidson, DM Eccles, T Cole, J Cook, J Paterson, C Brewer, F Douglas, SV Hodgson, PJ Morrison, L Walker, ME Porteous, MJ Kennedy, LE Side, B Bove, AK Godwin, D Stoppa-Lyonnet, M Fassy-Colcombet, L Castera, F Cornelis, S Mazoyer, M Leone, N Boutry-Kryza, B Bressac-de Paillerets, O (Olivier) Caron, P Pujol, I Coupier, C Delnatte, L Akloul, HT Lynch, CL Snyder, SS Buys, MB Daly, M Terry, WK Chung, EM John, A Miron, MC Southey, JL Hopper, DE Goldgar, CF Singer, C Rappaport, MKM Tea, A Fink-Retter, TVO Hansen, FC Nielsen, A Arason, J Vijai, S Shah, K Sarrel, ME Robson, M Piedmonte, K Phillips, J Basil, WS Rubinstein, J Boggess, K Wakeley, A Ewart-Toland, M Montagna, S Agata, EN Imyanitov, C Isaacs, R Janavicius, C (Conxi) Lazaro, I Blanco, L Feliubadalo, J Brunet, SA Gayther, PPD Pharoah, KO Odunsi, BY Karlan, CS Walsh, E Olah, SH Teo, PA Ganz, MS Beattie, EJ van Rensburg, CM Dorfling, 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, W Heinritz, T Caldes, M de la Hoya, TA Muranen, H Nevanlinna, M Tischkowitz, AB Spurdle, SL Neuhausen, YC Ding, NM Lindor, Z Fredericksen, VS Pankratz, P Peterlongo, S Manoukian, B Peissel, D Zaffaroni, M Barile, L Bernard, A Viel, G Giannini, L Varesco, P Radice, MH Greene, PL Mai, DF Easton, G Chenevix-Trench, K Offit, J Simard

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

41 Citations (Scopus)

Abstract

Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 x 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER) Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645-57. (C) 2012 AACR.

Original language	Undefined/Unknown
Pages (from-to)	645-657
Number of pages	13
Journal	Cancer Epidemiology Biomarkers & Prevention
Volume	21
Issue number	4
DOIs	https://doi.org/10.1158/1055-9965.EPI-11-0888
Publication status	Published - 2012

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10.1158/1055-9965.EPI-11-0888

http://hdl.handle.net/1765/66675

Cite this

Couch, FJ., Gaudet, MM., Antoniou, AC., Ramus, SJ., Kuchenbaecker, KB., Soucy, P., Beesley, J., Chen, XQ., Wang, XS., Kirchhoff, T., McGuffog, L., Barrowdale, D., Lee, A., Healey, S., Sinilnikova, OM., Andrulis, IL., Ozcelik, H., Mulligan, AM., Thomassen, M., ... Simard, J. (2012). Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. Cancer Epidemiology Biomarkers & Prevention, 21(4), 645-657. https://doi.org/10.1158/1055-9965.EPI-11-0888

@article{fc7ec99881054c02bb0c48fdb854fc80,

title = "Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers",

abstract = "Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 x 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER) Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645-57. (C) 2012 AACR.",

author = "FJ Couch and MM Gaudet and AC Antoniou and SJ Ramus and KB Kuchenbaecker and P Soucy and J Beesley and XQ Chen and XS Wang and T Kirchhoff and L McGuffog and D Barrowdale and A Lee and S Healey and OM Sinilnikova and IL Andrulis and H Ozcelik and AM Mulligan and Marga Thomassen and AM Gerdes and UB Jensen and AB Skytte and TA Kruse and MA Caligo and {von Wachenfeldt}, A and G Barbany-Bustinza and N Loman and M Soller and H Ehrencrona and P Karlsson and KL Nathanson and TR Rebbeck and SM Domchek and A Jakubowska and J Lubinski and K Jaworska and K Durda and E Zlowocka and T Huzarski and T Byrski and J Gronwald and C Cybulski and B Gorski and A Osorio and Duran, {M (Mercedes)} and MI Tejada and J Benitez and U Hamann and FBL Hogervorst and {van Os}, TA and {van Leeuwen}, FE and HEJ Meijers-Heijboer and {van Wijnen}, {J (Juul)} and MJ Blok and M Kets and Maartje Hooning and Rogier Oldenburg and MGEM Ausems and S Peock and D Frost and SD Ellis and R Platte and E Fineberg and DG Evans and C Jacobs and RA Eeles and J Adlard and R Davidson and DM Eccles and T Cole and J Cook and J Paterson and C Brewer and F Douglas and SV Hodgson and PJ Morrison and L Walker and ME Porteous and MJ Kennedy and LE Side and B Bove and AK Godwin and D Stoppa-Lyonnet and M Fassy-Colcombet and L Castera and F Cornelis and S Mazoyer and M Leone and N Boutry-Kryza and {Bressac-de Paillerets}, B and Caron, {O (Olivier)} and P Pujol and I Coupier and C Delnatte and L Akloul and HT Lynch and CL Snyder and SS Buys and MB Daly and M Terry and WK Chung and EM John and A Miron and MC Southey and JL Hopper and DE Goldgar and CF Singer and C Rappaport and MKM Tea and A Fink-Retter and TVO Hansen and FC Nielsen and A Arason and J Vijai and S Shah and K Sarrel and ME Robson and M Piedmonte and K Phillips and J Basil and WS Rubinstein and J Boggess and K Wakeley and A Ewart-Toland and M Montagna and S Agata and EN Imyanitov and C Isaacs and R Janavicius and Lazaro, {C (Conxi)} and I Blanco and L Feliubadalo and J Brunet and SA Gayther and PPD Pharoah and KO Odunsi and BY Karlan and CS Walsh and E Olah and SH Teo and PA Ganz and MS Beattie and {van Rensburg}, EJ and CM Dorfling 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 W Heinritz and T Caldes and {de la Hoya}, M and TA Muranen and H Nevanlinna and M Tischkowitz and AB Spurdle and SL Neuhausen and YC Ding and NM Lindor and Z Fredericksen and VS Pankratz and P Peterlongo and S Manoukian and B Peissel and D Zaffaroni and M Barile and L Bernard and A Viel and G Giannini and L Varesco and P Radice and MH Greene and PL Mai and DF Easton and G Chenevix-Trench and K Offit and J Simard",

year = "2012",

doi = "10.1158/1055-9965.EPI-11-0888",

language = "Undefined/Unknown",

volume = "21",

pages = "645--657",

journal = "Cancer Epidemiology Biomarkers and Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "4",

}

Couch, FJ, Gaudet, MM, Antoniou, AC, Ramus, SJ, Kuchenbaecker, KB, Soucy, P, Beesley, J, Chen, XQ, Wang, XS, Kirchhoff, T, McGuffog, L, Barrowdale, D, Lee, A, Healey, S, Sinilnikova, OM, Andrulis, IL, Ozcelik, H, Mulligan, AM, Thomassen, M, Gerdes, AM, Jensen, UB, Skytte, AB, Kruse, TA, Caligo, MA, von Wachenfeldt, A, Barbany-Bustinza, G, Loman, N, Soller, M, Ehrencrona, H, Karlsson, P, Nathanson, KL, Rebbeck, TR, Domchek, SM, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Zlowocka, E, Huzarski, T, Byrski, T, Gronwald, J, Cybulski, C, Gorski, B, Osorio, A, Duran, M, Tejada, MI, Benitez, J, Hamann, U, Hogervorst, FBL, van Os, TA, van Leeuwen, FE, Meijers-Heijboer, HEJ, van Wijnen, J, Blok, MJ, Kets, M, Hooning, M , Oldenburg, R, Ausems, MGEM, Peock, S, Frost, D, Ellis, SD, Platte, R, Fineberg, E, Evans, DG, Jacobs, C, Eeles, RA, Adlard, J, Davidson, R, Eccles, DM, Cole, T, Cook, J, Paterson, J, Brewer, C, Douglas, F, Hodgson, SV, Morrison, PJ, Walker, L, Porteous, ME, Kennedy, MJ, Side, LE, Bove, B, Godwin, AK, Stoppa-Lyonnet, D, Fassy-Colcombet, M, Castera, L, Cornelis, F, Mazoyer, S, Leone, M, Boutry-Kryza, N, Bressac-de Paillerets, B, Caron, O, Pujol, P, Coupier, I, Delnatte, C, Akloul, L, Lynch, HT, Snyder, CL, Buys, SS, Daly, MB, Terry, M, Chung, WK, John, EM, Miron, A, Southey, MC, Hopper, JL, Goldgar, DE, Singer, CF, Rappaport, C, Tea, MKM, Fink-Retter, A, Hansen, TVO, Nielsen, FC, Arason, A, Vijai, J, Shah, S, Sarrel, K, Robson, ME, Piedmonte, M, Phillips, K, Basil, J, Rubinstein, WS, Boggess, J, Wakeley, K, Ewart-Toland, A, Montagna, M, Agata, S, Imyanitov, EN, Isaacs, C, Janavicius, R, Lazaro, C, Blanco, I, Feliubadalo, L, Brunet, J, Gayther, SA, Pharoah, PPD, Odunsi, KO, Karlan, BY, Walsh, CS, Olah, E, Teo, SH, Ganz, PA, Beattie, MS, van Rensburg, EJ, Dorfling, CM, 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, Heinritz, W, Caldes, T, de la Hoya, M, Muranen, TA, Nevanlinna, H, Tischkowitz, M, Spurdle, AB, Neuhausen, SL, Ding, YC, Lindor, NM, Fredericksen, Z, Pankratz, VS, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Barile, M, Bernard, L, Viel, A, Giannini, G, Varesco, L, Radice, P, Greene, MH, Mai, PL, Easton, DF, Chenevix-Trench, G, Offit, K & Simard, J 2012, 'Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers', Cancer Epidemiology Biomarkers & Prevention, vol. 21, no. 4, pp. 645-657. https://doi.org/10.1158/1055-9965.EPI-11-0888

TY - JOUR

T1 - Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

AU - Couch, FJ

AU - Gaudet, MM

AU - Antoniou, AC

AU - Ramus, SJ

AU - Kuchenbaecker, KB

AU - Soucy, P

AU - Beesley, J

AU - Chen, XQ

AU - Wang, XS

AU - Kirchhoff, T

AU - McGuffog, L

AU - Barrowdale, D

AU - Lee, A

AU - Healey, S

AU - Sinilnikova, OM

AU - Andrulis, IL

AU - Ozcelik, H

AU - Mulligan, AM

AU - Thomassen, Marga

AU - Gerdes, AM

AU - Jensen, UB

AU - Skytte, AB

AU - Kruse, TA

AU - Caligo, MA

AU - von Wachenfeldt, A

AU - Barbany-Bustinza, G

AU - Loman, N

AU - Soller, M

AU - Ehrencrona, H

AU - Karlsson, P

AU - Nathanson, KL

AU - Rebbeck, TR

AU - Domchek, SM

AU - Jakubowska, A

AU - Lubinski, J

AU - Jaworska, K

AU - Durda, K

AU - Zlowocka, E

AU - Huzarski, T

AU - Byrski, T

AU - Gronwald, J

AU - Cybulski, C

AU - Gorski, B

AU - Osorio, A

AU - Duran, M (Mercedes)

AU - Tejada, MI

AU - Benitez, J

AU - Hamann, U

AU - Hogervorst, FBL

AU - van Os, TA

AU - van Leeuwen, FE

AU - Meijers-Heijboer, HEJ

AU - van Wijnen, J (Juul)

AU - Blok, MJ

AU - Kets, M

AU - Hooning, Maartje

AU - Oldenburg, Rogier

AU - Ausems, MGEM

AU - Peock, S

AU - Frost, D

AU - Ellis, SD

AU - Platte, R

AU - Fineberg, E

AU - Evans, DG

AU - Jacobs, C

AU - Eeles, RA

AU - Adlard, J

AU - Davidson, R

AU - Eccles, DM

AU - Cole, T

AU - Cook, J

AU - Paterson, J

AU - Brewer, C

AU - Douglas, F

AU - Hodgson, SV

AU - Morrison, PJ

AU - Walker, L

AU - Porteous, ME

AU - Kennedy, MJ

AU - Side, LE

AU - Bove, B

AU - Godwin, AK

AU - Stoppa-Lyonnet, D

AU - Fassy-Colcombet, M

AU - Castera, L

AU - Cornelis, F

AU - Mazoyer, S

AU - Leone, M

AU - Boutry-Kryza, N

AU - Bressac-de Paillerets, B

AU - Caron, O (Olivier)

AU - Pujol, P

AU - Coupier, I

AU - Delnatte, C

AU - Akloul, L

AU - Lynch, HT

AU - Snyder, CL

AU - Buys, SS

AU - Daly, MB

AU - Terry, M

AU - Chung, WK

AU - John, EM

AU - Miron, A

AU - Southey, MC

AU - Hopper, JL

AU - Goldgar, DE

AU - Singer, CF

AU - Rappaport, C

AU - Tea, MKM

AU - Fink-Retter, A

AU - Hansen, TVO

AU - Nielsen, FC

AU - Arason, A

AU - Vijai, J

AU - Shah, S

AU - Sarrel, K

AU - Robson, ME

AU - Piedmonte, M

AU - Phillips, K

AU - Basil, J

AU - Rubinstein, WS

AU - Boggess, J

AU - Wakeley, K

AU - Ewart-Toland, A

AU - Montagna, M

AU - Agata, S

AU - Imyanitov, EN

AU - Isaacs, C

AU - Janavicius, R

AU - Lazaro, C (Conxi)

AU - Blanco, I

AU - Feliubadalo, L

AU - Brunet, J

AU - Gayther, SA

AU - Pharoah, PPD

AU - Odunsi, KO

AU - Karlan, BY

AU - Walsh, CS

AU - Olah, E

AU - Teo, SH

AU - Ganz, PA

AU - Beattie, MS

AU - van Rensburg, EJ

AU - Dorfling, CM

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 - Heinritz, W

AU - Caldes, T

AU - de la Hoya, M

AU - Muranen, TA

AU - Nevanlinna, H

AU - Tischkowitz, M

AU - Spurdle, AB

AU - Neuhausen, SL

AU - Ding, YC

AU - Lindor, NM

AU - Fredericksen, Z

AU - Pankratz, VS

AU - Peterlongo, P

AU - Manoukian, S

AU - Peissel, B

AU - Zaffaroni, D

AU - Barile, M

AU - Bernard, L

AU - Viel, A

AU - Giannini, G

AU - Varesco, L

AU - Radice, P

AU - Greene, MH

AU - Mai, PL

AU - Easton, DF

AU - Chenevix-Trench, G

AU - Offit, K

AU - Simard, J

PY - 2012

Y1 - 2012

N2 - Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 x 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER) Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645-57. (C) 2012 AACR.

AB - Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 x 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER) Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645-57. (C) 2012 AACR.

U2 - 10.1158/1055-9965.EPI-11-0888

DO - 10.1158/1055-9965.EPI-11-0888

M3 - Article

VL - 21

SP - 645

EP - 657

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 4

ER -