Article: Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer

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TitleGenome-wide association study in east Asians identifies novel susceptibility loci for breast cancer
AuthorsLong, J3
Cai, Q3
Sung, H8
Shi, J3
Zhang, B3
Choi, JY8
Wen, W3
Delahanty, RJ3
Lu, W1
Gao, YT19
Shen, H10
Park, SK8
Chen, K22
Shen, CY6 21
Ren, Z14
Haiman, CA12
Matsuo, K9
Kim, MK5 13
Khoo, US4
Iwasaki, M18
Zheng, Y1
Xiang, YB19
Gu, K1
Rothman, N2
Wang, W1
Hu, Z10
Liu, Y10
Yoo, KY8
Noh, DY8
Han, BG20
Lee, MH15
Zheng, H22
Zhang, L22
Wu, PE21
Shieh, YL21
Chan, SY17
Wang, S14
Xie, X14
Kim, SW8
Henderson, BE12
Le Marchand, L11
Ito, H9
Kasuga, Y7
Ahn, SH5 13
Kang, HS5 13
Chan, KYK4
Iwata, H9
Tsugane, S18
Li, C16
Shu, XO3
Kang, DH8
Zheng, W3
KeywordsAsian
Breast cancer
Cancer risk
Cancer staging
Chinese
Issue Date2012
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
CitationPLoS Genetics, 2012, v. 8 n. 2, article no. e1002532 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pgen.1002532
AbstractGenetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-beta activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8x10(-12) in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85-0.94) and 0.80 (0.75-0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9x10(-6) from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6x10(-7)), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively.
ISSN1553-7390
2011 Impact Factor: 8.694
2011 SCImago Journal Rankings: 1.813
DOIhttp://dx.doi.org/10.1371/journal.pgen.1002532
PubMed Central IDPMC3285588
DC Field
Value
dc.contributor.authorLong, J
dc.contributor.authorCai, Q
dc.contributor.authorSung, H
dc.contributor.authorShi, J
dc.contributor.authorZhang, B
dc.contributor.authorChoi, JY
dc.contributor.authorWen, W
dc.contributor.authorDelahanty, RJ
dc.contributor.authorLu, W
dc.contributor.authorGao, YT
dc.contributor.authorShen, H
dc.contributor.authorPark, SK
dc.contributor.authorChen, K
dc.contributor.authorShen, CY
dc.contributor.authorRen, Z
dc.contributor.authorHaiman, CA
dc.contributor.authorMatsuo, K
dc.contributor.authorKim, MK
dc.contributor.authorKhoo, US
dc.contributor.authorIwasaki, M
dc.contributor.authorZheng, Y
dc.contributor.authorXiang, YB
dc.contributor.authorGu, K
dc.contributor.authorRothman, N
dc.contributor.authorWang, W
dc.contributor.authorHu, Z
dc.contributor.authorLiu, Y
dc.contributor.authorYoo, KY
dc.contributor.authorNoh, DY
dc.contributor.authorHan, BG
dc.contributor.authorLee, MH
dc.contributor.authorZheng, H
dc.contributor.authorZhang, L
dc.contributor.authorWu, PE
dc.contributor.authorShieh, YL
dc.contributor.authorChan, SY
dc.contributor.authorWang, S
dc.contributor.authorXie, X
dc.contributor.authorKim, SW
dc.contributor.authorHenderson, BE
dc.contributor.authorLe Marchand, L
dc.contributor.authorIto, H
dc.contributor.authorKasuga, Y
dc.contributor.authorAhn, SH
dc.contributor.authorKang, HS
dc.contributor.authorChan, KYK
dc.contributor.authorIwata, H
dc.contributor.authorTsugane, S
dc.contributor.authorLi, C
dc.contributor.authorShu, XO
dc.contributor.authorKang, DH
dc.contributor.authorZheng, W
dc.date.accessioned2012-09-20T08:10:04Z
dc.date.available2012-09-20T08:10:04Z
dc.date.issued2012
dc.description.abstractGenetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-beta activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8x10(-12) in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85-0.94) and 0.80 (0.75-0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9x10(-6) from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6x10(-7)), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively.
dc.description.naturepublished_or_final_version
dc.identifier.citationPLoS Genetics, 2012, v. 8 n. 2, article no. e1002532 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pgen.1002532
dc.identifier.citeulike10382027
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pgen.1002532
dc.identifier.hkuros206663
dc.identifier.issn1553-7390
2011 Impact Factor: 8.694
2011 SCImago Journal Rankings: 1.813
dc.identifier.issue2, article no. e1002532
dc.identifier.openurl
dc.identifier.pmcidPMC3285588
dc.identifier.pmid22383897
dc.identifier.scopuseid_2-s2.0-84859197861
dc.identifier.urihttp://hdl.handle.net/10722/164808
dc.identifier.volume8
dc.languageeng
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
dc.publisher.placeUnited States
dc.relation.ispartofPLoS Genetics
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
dc.subjectAsian
dc.subjectBreast cancer
dc.subjectCancer risk
dc.subjectCancer staging
dc.subjectChinese
dc.titleGenome-wide association study in east Asians identifies novel susceptibility loci for breast cancer
dc.typeArticle
Author Affiliations
  1. Shanghai Center for Disease Control and Prevention
  2. National Cancer Institute
  3. Vanderbilt Ingram Cancer Center
  4. The University of Hong Kong Li Ka Shing Faculty of Medicine
  5. National Cancer Center, Gyeonggi
  6. null
  7. Nagano Matsushiro General Hospital
  8. Seoul National University, College of Medical Sciences
  9. Aichi Cancer Center Hospital and Research Institute
  10. Nanjing Medical University
  11. University of Hawaii at Manoa
  12. Keck School of Medicine of USC
  13. University of Ulsan, College of Medicine
  14. Sun Yat-Sen University
  15. Soonchunhyang University, College of Medicine
  16. Vanderbilt University School of Medicine
  17. Queen Mary Hospital Hong Kong
  18. National Cancer Center Tokyo
  19. null
  20. National Institute of Health, Seoul
  21. Institute of Biomedical Sciences Academia Sinica Taiwan
  22. Tianjin Medical University