A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: Results from the Seoul Breast Cancer Study

Hyung cheol Kim; Ji Young Lee; Hyuna Sung; Ji Yeob Choi; Sue K. Park; Kyoung Mu Lee; Young J. Kim; Min J. Go; Lian Li; Yoon S. Cho; Miey Park; Dong Joon Kim; Ji H. Oh; Jun Woo Kim; Jae Pil Jeon; Soon Young Jeon; Haesook Min; Hyo M. Kim; Jaekyung Park; Keun Young Yoo; Dong Young Noh; Sei Hyun Ahn; Min H. Lee; Sung Won Kim; Jong W. Lee; Byeong Woo Park; Woong Yang Park; Eun Hye Kim; Mi K. Kim; Wonshik Han; Sang Ah Lee; Keitaro Matsuo; Chen Yang Shen; Pei Ei Wu; Chia Ni Hsiung; Jong Young Lee; Hyung Lae Kim; Bok Ghee Han; Daehee Kang

doi:10.1186/bcr3158

A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: Results from the Seoul Breast Cancer Study

Hyung cheol Kim, Ji Young Lee, Hyuna Sung, Ji Yeob Choi, Sue K. Park, Kyoung Mu Lee, Young J. Kim, Min J. Go, Lian Li, Yoon S. Cho, Miey Park, Dong Joon Kim, Ji H. Oh, Jun Woo Kim, Jae Pil Jeon, Soon Young Jeon, Haesook Min, Hyo M. Kim, Jaekyung Park, Keun Young YooDong Young Noh, Sei Hyun Ahn, Min H. Lee, Sung Won Kim, Jong W. Lee, Byeong Woo Park, Woong Yang Park, Eun Hye Kim, Mi K. Kim, Wonshik Han, Sang Ah Lee, Keitaro Matsuo, Chen Yang Shen, Pei Ei Wu, Chia Ni Hsiung, Jong Young Lee, Hyung Lae Kim, Bok Ghee Han, Daehee Kang

Department of Biochemistry

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

118 Scopus citations

Abstract

Introduction: Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.Methods: To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.Results: In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (P_trend< 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10^-14).Conclusions: This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.

Original language	English
Article number	R56
Journal	Breast Cancer Research
Volume	14
Issue number	2
DOIs	https://doi.org/10.1186/bcr3158
State	Published - 27 Mar 2012

Bibliographical note

Funding Information:
We thank all participants and investigators of the SeBCS, the Korean Hereditary Breast Cancer (KOHBRA) study, and the KoGES. This work was supported by a grant from the Ministry for Health, Welfare and Family Affairs, Republic of Korea (#2011-N73007-00) and by a grant from the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (#2012-0000347). The KOHBRA study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (#1020350).

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Kim, H. C., Lee, J. Y., Sung, H., Choi, J. Y., Park, S. K., Lee, K. M., Kim, Y. J., Go, M. J., Li, L., Cho, Y. S., Park, M., Kim, D. J., Oh, J. H., Kim, J. W., Jeon, J. P., Jeon, S. Y., Min, H., Kim, H. M., Park, J., ... Kang, D. (2012). A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: Results from the Seoul Breast Cancer Study. Breast Cancer Research, 14(2), Article R56. https://doi.org/10.1186/bcr3158

@article{7536ddccbf774c1db28b1f5531f8f741,

title = "A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: Results from the Seoul Breast Cancer Study",

abstract = "Introduction: Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.Methods: To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.Results: In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14).Conclusions: This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.",

author = "Kim, {Hyung cheol} and Lee, {Ji Young} and Hyuna Sung and Choi, {Ji Yeob} and Park, {Sue K.} and Lee, {Kyoung Mu} and Kim, {Young J.} and Go, {Min J.} and Lian Li and Cho, {Yoon S.} and Miey Park and Kim, {Dong Joon} and Oh, {Ji H.} and Kim, {Jun Woo} and Jeon, {Jae Pil} and Jeon, {Soon Young} and Haesook Min and Kim, {Hyo M.} and Jaekyung Park and Yoo, {Keun Young} and Noh, {Dong Young} and Ahn, {Sei Hyun} and Lee, {Min H.} and Kim, {Sung Won} and Lee, {Jong W.} and Park, {Byeong Woo} and Park, {Woong Yang} and Kim, {Eun Hye} and Kim, {Mi K.} and Wonshik Han and Lee, {Sang Ah} and Keitaro Matsuo and Shen, {Chen Yang} and Wu, {Pei Ei} and Hsiung, {Chia Ni} and Lee, {Jong Young} and Kim, {Hyung Lae} and Han, {Bok Ghee} and Daehee Kang",

note = "Funding Information: We thank all participants and investigators of the SeBCS, the Korean Hereditary Breast Cancer (KOHBRA) study, and the KoGES. This work was supported by a grant from the Ministry for Health, Welfare and Family Affairs, Republic of Korea (#2011-N73007-00) and by a grant from the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (#2012-0000347). The KOHBRA study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (#1020350).",

year = "2012",

month = mar,

day = "27",

doi = "10.1186/bcr3158",

language = "English",

volume = "14",

journal = "Breast Cancer Research",

issn = "1465-5411",

publisher = "BioMed Central Ltd.",

number = "2",

}

Kim, HC, Lee, JY, Sung, H, Choi, JY, Park, SK, Lee, KM, Kim, YJ, Go, MJ, Li, L, Cho, YS, Park, M, Kim, DJ, Oh, JH, Kim, JW, Jeon, JP, Jeon, SY, Min, H, Kim, HM, Park, J, Yoo, KY, Noh, DY, Ahn, SH, Lee, MH, Kim, SW, Lee, JW, Park, BW, Park, WY, Kim, EH, Kim, MK, Han, W, Lee, SA, Matsuo, K, Shen, CY, Wu, PE, Hsiung, CN, Lee, JY, Kim, HL, Han, BG & Kang, D 2012, 'A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: Results from the Seoul Breast Cancer Study', Breast Cancer Research, vol. 14, no. 2, R56. https://doi.org/10.1186/bcr3158

TY - JOUR

T1 - A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34

T2 - Results from the Seoul Breast Cancer Study

AU - Kim, Hyung cheol

AU - Lee, Ji Young

AU - Sung, Hyuna

AU - Choi, Ji Yeob

AU - Park, Sue K.

AU - Lee, Kyoung Mu

AU - Kim, Young J.

AU - Go, Min J.

AU - Li, Lian

AU - Cho, Yoon S.

AU - Park, Miey

AU - Kim, Dong Joon

AU - Oh, Ji H.

AU - Kim, Jun Woo

AU - Jeon, Jae Pil

AU - Jeon, Soon Young

AU - Min, Haesook

AU - Kim, Hyo M.

AU - Park, Jaekyung

AU - Yoo, Keun Young

AU - Noh, Dong Young

AU - Ahn, Sei Hyun

AU - Lee, Min H.

AU - Kim, Sung Won

AU - Lee, Jong W.

AU - Park, Byeong Woo

AU - Park, Woong Yang

AU - Kim, Eun Hye

AU - Kim, Mi K.

AU - Han, Wonshik

AU - Lee, Sang Ah

AU - Matsuo, Keitaro

AU - Shen, Chen Yang

AU - Wu, Pei Ei

AU - Hsiung, Chia Ni

AU - Lee, Jong Young

AU - Kim, Hyung Lae

AU - Han, Bok Ghee

AU - Kang, Daehee

N1 - Funding Information: We thank all participants and investigators of the SeBCS, the Korean Hereditary Breast Cancer (KOHBRA) study, and the KoGES. This work was supported by a grant from the Ministry for Health, Welfare and Family Affairs, Republic of Korea (#2011-N73007-00) and by a grant from the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (#2012-0000347). The KOHBRA study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (#1020350).

PY - 2012/3/27

Y1 - 2012/3/27

N2 - Introduction: Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.Methods: To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.Results: In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14).Conclusions: This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.

AB - Introduction: Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.Methods: To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.Results: In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14).Conclusions: This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.

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U2 - 10.1186/bcr3158

DO - 10.1186/bcr3158

M3 - Article

C2 - 23617951

AN - SCOPUS:84862815517

SN - 1465-5411

VL - 14

JO - Breast Cancer Research

JF - Breast Cancer Research

IS - 2

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ER -

A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: Results from the Seoul Breast Cancer Study

Abstract

Bibliographical note

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