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

TitleGenome-wide association study in east Asians identifies novel susceptibility loci for breast cancer
Authors
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/
Citation
PLoS Genetics, 2012, v. 8 n. 2, article no. e1002532 How to Cite?
Abstract
Genetic 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.
Persistent Identifierhttp://hdl.handle.net/10722/164808
ISSN
PubMed Central ID
ISI Accession Number ID

 

Author Affiliations
  1. Shanghai Center for Disease Control and Prevention
  2. The University of Hong Kong Li Ka Shing Faculty of Medicine
  3. Vanderbilt Ingram Cancer Center
  4. National Cancer Center, Gyeonggi
  5. National Cancer Institute
  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. Sun Yat-Sen University
  13. Soonchunhyang University, College of Medicine
  14. Keck School of Medicine of USC
  15. University of Ulsan, College of Medicine
  16. Queen Mary Hospital Hong Kong
  17. Vanderbilt University School of Medicine
  18. National Cancer Center Tokyo
  19. null
  20. National Institute of Health, Seoul
  21. Tianjin Medical University
  22. Institute of Biomedical Sciences Academia Sinica Taiwan
DC FieldValueLanguage
dc.contributor.authorLong, Jen_US
dc.contributor.authorCai, Qen_US
dc.contributor.authorSung, Hen_US
dc.contributor.authorShi, Jen_US
dc.contributor.authorZhang, Ben_US
dc.contributor.authorChoi, JYen_US
dc.contributor.authorWen, Wen_US
dc.contributor.authorDelahanty, RJen_US
dc.contributor.authorLu, Wen_US
dc.contributor.authorGao, YTen_US
dc.contributor.authorShen, Hen_US
dc.contributor.authorPark, SKen_US
dc.contributor.authorChen, Ken_US
dc.contributor.authorShen, CYen_US
dc.contributor.authorRen, Zen_US
dc.contributor.authorHaiman, CAen_US
dc.contributor.authorMatsuo, Ken_US
dc.contributor.authorKim, MKen_US
dc.contributor.authorKhoo, USen_US
dc.contributor.authorIwasaki, Men_US
dc.contributor.authorZheng, Yen_US
dc.contributor.authorXiang, YBen_US
dc.contributor.authorGu, Ken_US
dc.contributor.authorRothman, Nen_US
dc.contributor.authorWang, Wen_US
dc.contributor.authorHu, Zen_US
dc.contributor.authorLiu, Yen_US
dc.contributor.authorYoo, KYen_US
dc.contributor.authorNoh, DYen_US
dc.contributor.authorHan, BGen_US
dc.contributor.authorLee, MHen_US
dc.contributor.authorZheng, Hen_US
dc.contributor.authorZhang, Len_US
dc.contributor.authorWu, PEen_US
dc.contributor.authorShieh, YLen_US
dc.contributor.authorChan, SYen_US
dc.contributor.authorWang, Sen_US
dc.contributor.authorXie, Xen_US
dc.contributor.authorKim, SWen_US
dc.contributor.authorHenderson, BEen_US
dc.contributor.authorLe Marchand, Len_US
dc.contributor.authorIto, Hen_US
dc.contributor.authorKasuga, Yen_US
dc.contributor.authorAhn, SHen_US
dc.contributor.authorKang, HSen_US
dc.contributor.authorChan, KYKen_US
dc.contributor.authorIwata, Hen_US
dc.contributor.authorTsugane, Sen_US
dc.contributor.authorLi, Cen_US
dc.contributor.authorShu, XOen_US
dc.contributor.authorKang, DHen_US
dc.contributor.authorZheng, Wen_US
dc.date.accessioned2012-09-20T08:10:04Z-
dc.date.available2012-09-20T08:10:04Z-
dc.date.issued2012en_US
dc.identifier.citationPLoS Genetics, 2012, v. 8 n. 2, article no. e1002532en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://hdl.handle.net/10722/164808-
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.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/-
dc.relation.ispartofPLoS Geneticsen_US
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 canceren_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1553-7404 (Electronic) 1553-7390 (Linkin&volume=8&issue=2&spage=e1002532&epage=&date=2012&atitle=Genome-wide+association+study+in+east+Asians+identifies+novel+susceptibility+loci+for+breast+canceren_US
dc.identifier.emailKhoo, US: uskhoo@hkucc.hku.hken_US
dc.identifier.emailChan, KYK: ykchanc@hku.hken_US
dc.identifier.authorityKhoo, US=rp00362en_US
dc.identifier.authorityChan, KYK=rp00453en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pgen.1002532-
dc.identifier.pmid22383897-
dc.identifier.pmcidPMC3285588-
dc.identifier.scopuseid_2-s2.0-84859197861-
dc.identifier.hkuros206663en_US
dc.identifier.volume8en_US
dc.identifier.issue2, article no. e1002532en_US
dc.identifier.isiWOS:000300725500045-
dc.publisher.placeUnited States-
dc.identifier.citeulike10382027-

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