A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

A Siddiq; FJ Couch; GK Chen; S Lindstrom; D Eccles; RC Millikan; K Michailidou; DO Stram; L Beckmann; SK Rhie; CB Ambrosone; K Aittomaki; P Amiano; C Apicella; L Baglietto; EV Bandera; MW Beckmann; CD Berg; L Bernstein; C Blomqvist; H Brauch; L Brinton; QM Bui; JE Buring; SS Buys; D Campa; JE Carpenter; DI Chasman; J Chang-Claude; Constance Chen; F Clavel-Chapelon; A Cox; SS Cross; K Czene; SL Deming; RB Diasio; WR Diver; AM Dunning; L Durcan; AB Ekici; PA Fasching; HS Feigelson; L Fejerman; JD Figueroa; O Fletcher; D Flesch-Janys; MM Gaudet; SM Gerty; JL Rodriguez-Gil; GG Giles; CH van Gils; AK Godwin; N Graham; D Greco; P Hall; SE Hankinson; A Hartmann; R Hein; J Heinz; RN Hoover; JL Hopper; JJ Hu; S Huntsman; SA Ingles; A Irwanto; C Isaacs; KB Jacobs; EM John; C Justenhoven; R Kaaks; LN Kolonel; GA Coetzee; M Lathrop; L Le Marchand; AM Lee; IM Lee; T Lesnick; P Lichtner; JJ Liu; E Lund; E Makalic; NG Martin; CA McLean; H Meijers-Heijboer; A Meindl; P Miron; KR Monroe; GW Montgomery; B Muller-Myhsok; S Nickels; SJ Nyante; C Olswold; K Overvad; D Palli; DJ Park; JR Palmer; H Pathak; J Peto; P Pharoah; N Rahman; Fernando Rivadeneira; DF Schmidt; RK Schmutzler; S Slager; MC Southey; KN Stevens; HP Sinn; MF Press; E Ross; E Riboli; PM Ridker; FR Schumacher; G Severi; ID Silva; J Stone; M Sund; WJ Tapper; MJ Thun; RC Travis; C Turnbull; André Uitterlinden; Q Waisfisz; XS Wang; ZM Wang; J Weaver; R Schulz-Wendtland; LR Wilkens; D van den Berg; W Zheng; RG Ziegler; E Ziv; H Nevanlinna; DF Easton; DJ Hunter; BE Henderson; SJ Chanock; M Garcia-Closas; P Kraft; CA Haiman; CM Vachon

doi:10.1093/hmg/dds381

A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

A Siddiq, FJ Couch, GK Chen, S Lindstrom, D Eccles, RC Millikan, K Michailidou, DO Stram, L Beckmann, SK Rhie, CB Ambrosone, K Aittomaki, P Amiano, C Apicella, L Baglietto, EV Bandera, MW Beckmann, CD Berg, L Bernstein, C BlomqvistH Brauch, L Brinton, QM Bui, JE Buring, SS Buys, D Campa, JE Carpenter, DI Chasman, J Chang-Claude, Constance Chen, F Clavel-Chapelon, A Cox, SS Cross, K Czene, SL Deming, RB Diasio, WR Diver, AM Dunning, L Durcan, AB Ekici, PA Fasching, HS Feigelson, L Fejerman, JD Figueroa, O Fletcher, D Flesch-Janys, MM Gaudet, SM Gerty, JL Rodriguez-Gil, GG Giles, CH van Gils, AK Godwin, N Graham, D Greco, P Hall, SE Hankinson, A Hartmann, R Hein, J Heinz, RN Hoover, JL Hopper, JJ Hu, S Huntsman, SA Ingles, A Irwanto, C Isaacs, KB Jacobs, EM John, C Justenhoven, R Kaaks, LN Kolonel, GA Coetzee, M Lathrop, L Le Marchand, AM Lee, IM Lee, T Lesnick, P Lichtner, JJ Liu, E Lund, E Makalic, NG Martin, CA McLean, H Meijers-Heijboer, A Meindl, P Miron, KR Monroe, GW Montgomery, B Muller-Myhsok, S Nickels, SJ Nyante, C Olswold, K Overvad, D Palli, DJ Park, JR Palmer, H Pathak, J Peto, P Pharoah, N Rahman, Fernando Rivadeneira, DF Schmidt, RK Schmutzler, S Slager, MC Southey, KN Stevens, HP Sinn, MF Press, E Ross, E Riboli, PM Ridker, FR Schumacher, G Severi, ID Silva, J Stone, M Sund, WJ Tapper, MJ Thun, RC Travis, C Turnbull, André Uitterlinden, Q Waisfisz, XS Wang, ZM Wang, J Weaver, R Schulz-Wendtland, LR Wilkens, D van den Berg, W Zheng, RG Ziegler, E Ziv, H Nevanlinna, DF Easton, DJ Hunter, BE Henderson, SJ Chanock, M Garcia-Closas, P Kraft, CA Haiman, CM Vachon

Internal Medicine

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

141 Citations (Scopus)

Abstract

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P 1 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR 1.16; P 1.1 10(8)) but showed a weaker association with overall breast cancer (OR 1.08, P 1.3 10(6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR 1.01, P 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR 1.12; P 1.1 10(9)), and with both ER-positive (OR 1.09; P 1.5 10(5)) and ER-negative (OR 1.16, P 2.5 10(7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

Original language	Undefined/Unknown
Pages (from-to)	5373-5384
Number of pages	12
Journal	Human Molecular Genetics
Volume	21
Issue number	24
DOIs	https://doi.org/10.1093/hmg/dds381
Publication status	Published - 2012

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10.1093/hmg/dds381

http://hdl.handle.net/1765/54129

Cite this

Siddiq, A., Couch, FJ., Chen, GK., Lindstrom, S., Eccles, D., Millikan, RC., Michailidou, K., Stram, DO., Beckmann, L., Rhie, SK., Ambrosone, CB., Aittomaki, K., Amiano, P., Apicella, C., Baglietto, L., Bandera, EV., Beckmann, MW., Berg, CD., Bernstein, L., ... Vachon, CM. (2012). A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11. Human Molecular Genetics, 21(24), 5373-5384. https://doi.org/10.1093/hmg/dds381

@article{67bfde168d724ba1a81c81f236e8fb8e,

title = "A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11",

abstract = "Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P 1 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR 1.16; P 1.1 10(8)) but showed a weaker association with overall breast cancer (OR 1.08, P 1.3 10(6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR 1.01, P 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR 1.12; P 1.1 10(9)), and with both ER-positive (OR 1.09; P 1.5 10(5)) and ER-negative (OR 1.16, P 2.5 10(7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.",

author = "A Siddiq and FJ Couch and GK Chen and S Lindstrom and D Eccles and RC Millikan and K Michailidou and DO Stram and L Beckmann and SK Rhie and CB Ambrosone and K Aittomaki and P Amiano and C Apicella and L Baglietto and EV Bandera and MW Beckmann and CD Berg and L Bernstein and C Blomqvist and H Brauch and L Brinton and QM Bui and JE Buring and SS Buys and D Campa and JE Carpenter and DI Chasman and J Chang-Claude and Constance Chen and F Clavel-Chapelon and A Cox and SS Cross and K Czene and SL Deming and RB Diasio and WR Diver and AM Dunning and L Durcan and AB Ekici and PA Fasching and HS Feigelson and L Fejerman and JD Figueroa and O Fletcher and D Flesch-Janys and MM Gaudet and SM Gerty and JL Rodriguez-Gil and GG Giles and {van Gils}, CH and AK Godwin and N Graham and D Greco and P Hall and SE Hankinson and A Hartmann and R Hein and J Heinz and RN Hoover and JL Hopper and JJ Hu and S Huntsman and SA Ingles and A Irwanto and C Isaacs and KB Jacobs and EM John and C Justenhoven and R Kaaks and LN Kolonel and GA Coetzee and M Lathrop and {Le Marchand}, L and AM Lee and IM Lee and T Lesnick and P Lichtner and JJ Liu and E Lund and E Makalic and NG Martin and CA McLean and H Meijers-Heijboer and A Meindl and P Miron and KR Monroe and GW Montgomery and B Muller-Myhsok and S Nickels and SJ Nyante and C Olswold and K Overvad and D Palli and DJ Park and JR Palmer and H Pathak and J Peto and P Pharoah and N Rahman and Fernando Rivadeneira and DF Schmidt and RK Schmutzler and S Slager and MC Southey and KN Stevens and HP Sinn and MF Press and E Ross and E Riboli and PM Ridker and FR Schumacher and G Severi and ID Silva and J Stone and M Sund and WJ Tapper and MJ Thun and RC Travis and C Turnbull and Andr{\'e} Uitterlinden and Q Waisfisz and XS Wang and ZM Wang and J Weaver and R Schulz-Wendtland and LR Wilkens and {van den Berg}, D and W Zheng and RG Ziegler and E Ziv and H Nevanlinna and DF Easton and DJ Hunter and BE Henderson and SJ Chanock and M Garcia-Closas and P Kraft and CA Haiman and CM Vachon",

year = "2012",

doi = "10.1093/hmg/dds381",

language = "Undefined/Unknown",

volume = "21",

pages = "5373--5384",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "24",

}

Siddiq, A, Couch, FJ, Chen, GK, Lindstrom, S, Eccles, D, Millikan, RC, Michailidou, K, Stram, DO, Beckmann, L, Rhie, SK, Ambrosone, CB, Aittomaki, K, Amiano, P, Apicella, C, Baglietto, L, Bandera, EV, Beckmann, MW, Berg, CD, Bernstein, L, Blomqvist, C, Brauch, H, Brinton, L, Bui, QM, Buring, JE, Buys, SS, Campa, D, Carpenter, JE, Chasman, DI, Chang-Claude, J, Chen, C, Clavel-Chapelon, F, Cox, A, Cross, SS, Czene, K, Deming, SL, Diasio, RB, Diver, WR, Dunning, AM, Durcan, L, Ekici, AB, Fasching, PA, Feigelson, HS, Fejerman, L, Figueroa, JD, Fletcher, O, Flesch-Janys, D, Gaudet, MM, Gerty, SM, Rodriguez-Gil, JL, Giles, GG, van Gils, CH, Godwin, AK, Graham, N, Greco, D, Hall, P, Hankinson, SE, Hartmann, A, Hein, R, Heinz, J, Hoover, RN, Hopper, JL, Hu, JJ, Huntsman, S, Ingles, SA, Irwanto, A, Isaacs, C, Jacobs, KB, John, EM, Justenhoven, C, Kaaks, R, Kolonel, LN, Coetzee, GA, Lathrop, M, Le Marchand, L, Lee, AM, Lee, IM, Lesnick, T, Lichtner, P, Liu, JJ, Lund, E, Makalic, E, Martin, NG, McLean, CA, Meijers-Heijboer, H, Meindl, A, Miron, P, Monroe, KR, Montgomery, GW, Muller-Myhsok, B, Nickels, S, Nyante, SJ, Olswold, C, Overvad, K, Palli, D, Park, DJ, Palmer, JR, Pathak, H, Peto, J, Pharoah, P, Rahman, N, Rivadeneira, F, Schmidt, DF, Schmutzler, RK, Slager, S, Southey, MC, Stevens, KN, Sinn, HP, Press, MF, Ross, E, Riboli, E, Ridker, PM, Schumacher, FR, Severi, G, Silva, ID, Stone, J, Sund, M, Tapper, WJ, Thun, MJ, Travis, RC, Turnbull, C, Uitterlinden, A, Waisfisz, Q, Wang, XS, Wang, ZM, Weaver, J, Schulz-Wendtland, R, Wilkens, LR, van den Berg, D, Zheng, W, Ziegler, RG, Ziv, E, Nevanlinna, H, Easton, DF, Hunter, DJ, Henderson, BE, Chanock, SJ, Garcia-Closas, M, Kraft, P, Haiman, CA & Vachon, CM 2012, 'A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11', Human Molecular Genetics, vol. 21, no. 24, pp. 5373-5384. https://doi.org/10.1093/hmg/dds381

TY - JOUR

T1 - A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

AU - Siddiq, A

AU - Couch, FJ

AU - Chen, GK

AU - Lindstrom, S

AU - Eccles, D

AU - Millikan, RC

AU - Michailidou, K

AU - Stram, DO

AU - Beckmann, L

AU - Rhie, SK

AU - Ambrosone, CB

AU - Aittomaki, K

AU - Amiano, P

AU - Apicella, C

AU - Baglietto, L

AU - Bandera, EV

AU - Beckmann, MW

AU - Berg, CD

AU - Bernstein, L

AU - Blomqvist, C

AU - Brauch, H

AU - Brinton, L

AU - Bui, QM

AU - Buring, JE

AU - Buys, SS

AU - Campa, D

AU - Carpenter, JE

AU - Chasman, DI

AU - Chang-Claude, J

AU - Chen, Constance

AU - Clavel-Chapelon, F

AU - Cox, A

AU - Cross, SS

AU - Czene, K

AU - Deming, SL

AU - Diasio, RB

AU - Diver, WR

AU - Dunning, AM

AU - Durcan, L

AU - Ekici, AB

AU - Fasching, PA

AU - Feigelson, HS

AU - Fejerman, L

AU - Figueroa, JD

AU - Fletcher, O

AU - Flesch-Janys, D

AU - Gaudet, MM

AU - Gerty, SM

AU - Rodriguez-Gil, JL

AU - Giles, GG

AU - van Gils, CH

AU - Godwin, AK

AU - Graham, N

AU - Greco, D

AU - Hall, P

AU - Hankinson, SE

AU - Hartmann, A

AU - Hein, R

AU - Heinz, J

AU - Hoover, RN

AU - Hopper, JL

AU - Hu, JJ

AU - Huntsman, S

AU - Ingles, SA

AU - Irwanto, A

AU - Isaacs, C

AU - Jacobs, KB

AU - John, EM

AU - Justenhoven, C

AU - Kaaks, R

AU - Kolonel, LN

AU - Coetzee, GA

AU - Lathrop, M

AU - Le Marchand, L

AU - Lee, AM

AU - Lee, IM

AU - Lesnick, T

AU - Lichtner, P

AU - Liu, JJ

AU - Lund, E

AU - Makalic, E

AU - Martin, NG

AU - McLean, CA

AU - Meijers-Heijboer, H

AU - Meindl, A

AU - Miron, P

AU - Monroe, KR

AU - Montgomery, GW

AU - Muller-Myhsok, B

AU - Nickels, S

AU - Nyante, SJ

AU - Olswold, C

AU - Overvad, K

AU - Palli, D

AU - Park, DJ

AU - Palmer, JR

AU - Pathak, H

AU - Peto, J

AU - Pharoah, P

AU - Rahman, N

AU - Rivadeneira, Fernando

AU - Schmidt, DF

AU - Schmutzler, RK

AU - Slager, S

AU - Southey, MC

AU - Stevens, KN

AU - Sinn, HP

AU - Press, MF

AU - Ross, E

AU - Riboli, E

AU - Ridker, PM

AU - Schumacher, FR

AU - Severi, G

AU - Silva, ID

AU - Stone, J

AU - Sund, M

AU - Tapper, WJ

AU - Thun, MJ

AU - Travis, RC

AU - Turnbull, C

AU - Uitterlinden, André

AU - Waisfisz, Q

AU - Wang, XS

AU - Wang, ZM

AU - Weaver, J

AU - Schulz-Wendtland, R

AU - Wilkens, LR

AU - van den Berg, D

AU - Zheng, W

AU - Ziegler, RG

AU - Ziv, E

AU - Nevanlinna, H

AU - Easton, DF

AU - Hunter, DJ

AU - Henderson, BE

AU - Chanock, SJ

AU - Garcia-Closas, M

AU - Kraft, P

AU - Haiman, CA

AU - Vachon, CM

PY - 2012

Y1 - 2012

N2 - Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P 1 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR 1.16; P 1.1 10(8)) but showed a weaker association with overall breast cancer (OR 1.08, P 1.3 10(6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR 1.01, P 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR 1.12; P 1.1 10(9)), and with both ER-positive (OR 1.09; P 1.5 10(5)) and ER-negative (OR 1.16, P 2.5 10(7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

AB - Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P 1 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR 1.16; P 1.1 10(8)) but showed a weaker association with overall breast cancer (OR 1.08, P 1.3 10(6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR 1.01, P 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR 1.12; P 1.1 10(9)), and with both ER-positive (OR 1.09; P 1.5 10(5)) and ER-negative (OR 1.16, P 2.5 10(7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

U2 - 10.1093/hmg/dds381

DO - 10.1093/hmg/dds381

M3 - Article

SN - 0964-6906

VL - 21

SP - 5373

EP - 5384

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 24

ER -