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Article: Genome-wide association study identifies breast cancer risk variant at 10q21.2: Results from the asia breast cancer consortium

TitleGenome-wide association study identifies breast cancer risk variant at 10q21.2: Results from the asia breast cancer consortium
Authors
Issue Date2011
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2011, v. 20 n. 24, p. 4991-4999 How to Cite?
Abstract
Although approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07-1.14) (P-value for trend = 5.87 × 10 -9). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women. © The Author 2011. Published by Oxford University Press. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/148660
ISSN
2013 Impact Factor: 6.677
ISI Accession Number ID
Funding AgencyGrant Number
US National Institutes of HealthR01CA124558
R01CA064277
R37CA070867
R01CA090899
R01CA100374
Ingram Professorship
Research Reward funds
Department of Defense (DOD)BC011118
BC050791
Shanghai Breast Cancer StudyR01CA064277
Shanghai Breast Cancer Survival StudyR01CA118229
Shanghai Endometrial Cancer StudyR01CA092585
Seoul Breast Cancer Study (Basic Research Laboratory (BRL)) through the National Research Foundation of Korea
Ministry of Education, Science and Technology2011-0001564
Korean Hereditary Breast Cancer Study/Korean Genome and Epidemiology Study (Ministry for Health, Welfare and Family Affairs, Republic of Korea)1020350
Tianjin Study (National Natural Science Foundation of China)30771844
Nanjing Study (Jiangsu, China)09KJA330001
Taiwan Biobank StudyDOH97-01
Hong Kong Study (Research Grant Council, Hong Kong SAR, China)HKU 7520/05M
76730M
Guangzhou Breast Cancer Study (National Natural Science Foundation of China)81072383
Multiethnic Cohort StudyCA063464
CA054281
CA132839
Nagano Breast Cancer Study (Ministry of Health, Labor and Welfare of Japan)17015049
H20-002
Nagano Breast Cancer Study (Ministry of Education, Culture, Sports, Science, and Technology of Japan)221S0001
Vanderbilt-Ingram Cancer CenterP30 CA068485
R01CA122756
Funding Information:

This research was supported in part by US National Institutes of Health grants R01CA124558, R01CA064277, R37CA070867, R01CA090899 and R01CA100374, as well as Ingram Professorship and Research Reward funds awarded to W.Z.; R01CA118229, R01CA092585, and Department of Defense (DOD) Idea Award BC011118 awarded to X.-O.S.; and R01CA122756 and DOD Idea Award BC050791 awarded to Q. C. Participating studies (principal investigator, grant support) in the consortium are as follows: the Shanghai Breast Cancer Study (W.Z., R01CA064277), the Shanghai Breast Cancer Survival Study (X.-O.S., R01CA118229), the Shanghai Endometrial Cancer Study (X.-O.S., R01CA092585, contributed only controls to the consortium), the Seoul Breast Cancer Study [D. K., Basic Research Laboratory (BRL) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology, 2011-0001564], the Korean Hereditary Breast Cancer Study/Korean Genome and Epidemiology Study (S.-W.K., the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea, 1020350), the Tianjin Study (K. C., the National Natural Science Foundation of China Grant No. 30771844), the Nanjing Study (H. S., 09KJA330001, Jiangsu, China), the Taiwan Biobank Study (C.-Y.S., DOH97-01), the Hong Kong Study (U.S.K., Research Grant Council, Hong Kong SAR, China, HKU 7520/05M and 76730M), the Guangzhou Breast Cancer Study (Z.R., the National Natural Science Foundation of China, 81072383), the Multiethnic Cohort Study (B. E. H., CA063464; L. K., CA054281; and C. H., CA132839), the Nagano Breast Cancer Study (S. T., Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, for Scientific Research on Priority Areas, 17015049 and for Scientific Research on Innovative Areas, 221S0001, from the Ministry of Education, Culture, Sports, Science, and Technology of Japan) and the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (K. T., Grants-in-Aid for Scientific Research on Priority Areas, 17015052, from the Ministry of Education, Culture, Sports, Science, and Technology of Japan H. T., Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, H20-002). Sample preparation and genotyping assays at Vanderbilt were conducted at the Survey and Biospecimen Shared Resources and Vanderbilt Microarray Shared Resource, which are supported in part by Vanderbilt-Ingram Cancer Center (P30 CA068485).

References
Grants

 

Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Vanderbilt Ingram Cancer Center
  3. Shanghai Municipal Center for Disease Control and Prevention
  4. HudsonAlpha Institute for Biotechnology
  5. Seoul National University Bundang Hospital
  6. Nagano Matsushiro General Hospital
  7. Seoul National University, College of Medical Sciences
  8. Aichi Cancer Center Hospital and Research Institute
  9. Soonchunhyang University
  10. Nanjing Medical University
  11. University of Hawaii at Manoa
  12. Sun Yat-Sen University
  13. University of Ulsan, College of Medicine
  14. Vanderbilt University School of Medicine
  15. National Cancer Center Tokyo
  16. null
  17. National Institute of Health, Seoul
  18. Tianjin Medical University
  19. Institute of Biomedical Sciences Academia Sinica Taiwan
  20. University of Southern California/Norris Comprehensive Cancer Center
DC FieldValueLanguage
dc.contributor.authorCai, Qen_US
dc.contributor.authorLong, Jen_US
dc.contributor.authorLu, Wen_US
dc.contributor.authorQu, Sen_US
dc.contributor.authorWen, Wen_US
dc.contributor.authorKang, Den_US
dc.contributor.authorLee, JYen_US
dc.contributor.authorChen, Ken_US
dc.contributor.authorShen, Hen_US
dc.contributor.authorShen, Cen_US
dc.contributor.authorSung, Hen_US
dc.contributor.authorMatsuo, Ken_US
dc.contributor.authorHaiman, CAen_US
dc.contributor.authorKhoo, USen_US
dc.contributor.authorRen, Zen_US
dc.contributor.authorIwasaki, Men_US
dc.contributor.authorGu, Ken_US
dc.contributor.authorXiang, YBen_US
dc.contributor.authorChoi, JYen_US
dc.contributor.authorPark, SKen_US
dc.contributor.authorZhang, Len_US
dc.contributor.authorHu, Zen_US
dc.contributor.authorWu, PEen_US
dc.contributor.authorNoh, Den_US
dc.contributor.authorTajima, Ken_US
dc.contributor.authorHenderson, BEen_US
dc.contributor.authorChan, KYen_US
dc.contributor.authorSu, Fen_US
dc.contributor.authorKasuga, Yen_US
dc.contributor.authorWang, Wen_US
dc.contributor.authorCheng, JRen_US
dc.contributor.authorYoo, KYen_US
dc.contributor.authorLee, JYen_US
dc.contributor.authorZheng, Hen_US
dc.contributor.authorLiu, Yen_US
dc.contributor.authorShieh, YLen_US
dc.contributor.authorKim, SWen_US
dc.contributor.authorLee, JWen_US
dc.contributor.authorIwata, Hen_US
dc.contributor.authorMarchand, LLen_US
dc.contributor.authorChan, SYen_US
dc.contributor.authorXie, Xen_US
dc.contributor.authorTsugane, Sen_US
dc.contributor.authorLee, MHen_US
dc.contributor.authorWang, Sen_US
dc.contributor.authorLi, Gen_US
dc.contributor.authorLevy, Sen_US
dc.contributor.authorHuang, Ben_US
dc.contributor.authorShi, Jen_US
dc.contributor.authorDelahanty, Ren_US
dc.contributor.authorZheng, Yen_US
dc.contributor.authorLi, Cen_US
dc.contributor.authorGao, YTen_US
dc.contributor.authorShu, XOen_US
dc.contributor.authorZheng, Wen_US
dc.date.accessioned2012-05-29T06:14:30Z-
dc.date.available2012-05-29T06:14:30Z-
dc.date.issued2011en_US
dc.identifier.citationHuman Molecular Genetics, 2011, v. 20 n. 24, p. 4991-4999en_US
dc.identifier.issn0964-6906en_US
dc.identifier.urihttp://hdl.handle.net/10722/148660-
dc.description.abstractAlthough approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07-1.14) (P-value for trend = 5.87 × 10 -9). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women. © The Author 2011. Published by Oxford University Press. All rights reserved.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/en_US
dc.relation.ispartofHuman Molecular Geneticsen_US
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAllelesen_US
dc.subject.meshAsiaen_US
dc.subject.meshBreast Neoplasms - Geneticsen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshChromosomes, Human, Pair 10 - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGenetic Predisposition To Diseaseen_US
dc.subject.meshGenome-Wide Association Studyen_US
dc.subject.meshHumansen_US
dc.subject.meshMenopause - Geneticsen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshOdds Ratioen_US
dc.subject.meshPolymorphism, Single Nucleotide - Geneticsen_US
dc.titleGenome-wide association study identifies breast cancer risk variant at 10q21.2: Results from the asia breast cancer consortiumen_US
dc.typeArticleen_US
dc.identifier.emailKhoo, US:uskhoo@hkucc.hku.hken_US
dc.identifier.authorityKhoo, US=rp00362en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1093/hmg/ddr405en_US
dc.identifier.pmid21908515en_US
dc.identifier.scopuseid_2-s2.0-81855226435en_US
dc.identifier.hkuros206656-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-81855226435&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume20en_US
dc.identifier.issue24en_US
dc.identifier.spage4991en_US
dc.identifier.epage4999en_US
dc.identifier.isiWOS:000297242100018-
dc.publisher.placeUnited Kingdomen_US
dc.relation.projectGene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility-

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