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Article: Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium.

TitleIdentification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium.
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
Citation
Plos Genetics, 2010, v. 6 n. 6, p. e1001002 How to Cite?
AbstractGenetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20-1.31) per allele (P = 3.2 x 10(-25)) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR = 1.19, 95% CI = 1.09-1.31, P = 1.3 x 10(-4), 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures.
Persistent Identifierhttp://hdl.handle.net/10722/126685
ISSN
2015 Impact Factor: 6.661
2015 SCImago Journal Rankings: 6.308
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
NIHR01CA124558
R01CA64277
R01CA70867
R01CA90899
R01CA100374
R01CA118229
R01CA122756
Shanghai Breast Cancer StudyR01CA64277
Shanghai Breast Cancer Survival StudyR01CA118229
Shanghai Endometrial Cancer StudyR01CA92585
Nashville Breast Health StudyR01CA100374
Tianjin Study30771844
Nanjing Study, ChinaIRT0631
Taiwan Biobank StudyDOH97-01
Hong Kong StudyHKU 7520/05 M
76730 M
Multiethnic Cohort StudyCA63464
CA54281
CA132839
Ministry of Education, Culture, Sports, Science, and Technology of Japan17015049
17015052
Ministry of Health, Labor and Welfare of JapanH20-002
Funding Information:

Genotyping assays and statistical analyses for this research were supported primarily through NIH grants R01CA124558, R01CA64277, R01CA70867, R01CA90899, and R01CA100374 (WZ), R01CA118229 (X-OS), and R01CA122756 (QC). Participating studies (Principal Investigator, grant support) in the consortium are as follows: the Shanghai Breast Cancer Study (WZ, R01CA64277), the Shanghai Breast Cancer Survival Study (X-OS, R01CA118229), the Shanghai Endometrial Cancer Study (X-OS, R01CA92585, contributing only controls to the consortium), the Nashville Breast Health Study (WZ, R01CA100374), the Tianjin Study (KC, the National Natural Science Foundation of China Grant No. 30771844), the Nanjing Study (HS, IRT0631, China), the Taiwan Biobank Study (C-YS, DOH97-01), the Hong Kong Study (USK, Research Grant Council, Hong Kong SAR, China, HKU 7520/05 M and 76730 M), the Multiethnic Cohort Study (BEH, CA63464; L. Kolonel, CA54281; and CAH, CA132839), the Nagano Breast Cancer Study (ST, Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, and for Scientific Research on Priority Areas (17015049) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan), the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (KT, Grants-in-Aid for Scientific Research on Priority Areas (17015052) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan H. Tanaka, 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). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 

DC FieldValueLanguage
dc.contributor.authorLong, Jen_HK
dc.contributor.authorCai, Qen_HK
dc.contributor.authorShu, XOen_HK
dc.contributor.authorQu, Sen_HK
dc.contributor.authorLi, Cen_HK
dc.contributor.authorZheng, Yen_HK
dc.contributor.authorGu, Ken_HK
dc.contributor.authorWang, Wen_HK
dc.contributor.authorXiang, YBen_HK
dc.contributor.authorCheng, Jen_HK
dc.contributor.authorChen, Ken_HK
dc.contributor.authorZhang, Len_HK
dc.contributor.authorZheng, Hen_HK
dc.contributor.authorShen, CYen_HK
dc.contributor.authorHuang, CSen_HK
dc.contributor.authorHou, MFen_HK
dc.contributor.authorShen, Hen_HK
dc.contributor.authorHu, Zen_HK
dc.contributor.authorWang, Fen_HK
dc.contributor.authorDeming, SLen_HK
dc.contributor.authorKelley, MCen_HK
dc.contributor.authorShrubsole, MJen_HK
dc.contributor.authorKhoo, USen_HK
dc.contributor.authorChan, KYen_HK
dc.contributor.authorChan, SYen_HK
dc.contributor.authorHaiman, CAen_HK
dc.contributor.authorHenderson, BEen_HK
dc.contributor.authorle Marchand, Len_HK
dc.contributor.authorIwasaki, Men_HK
dc.contributor.authorKasuga, Yen_HK
dc.contributor.authorTsugane, Sen_HK
dc.contributor.authorMatsuo, Ken_HK
dc.contributor.authorTajima, Ken_HK
dc.contributor.authorIwata, Hen_HK
dc.contributor.authorHuang, Ben_HK
dc.contributor.authorShi, Jen_HK
dc.contributor.authorLi, Gen_HK
dc.contributor.authorWen, Wen_HK
dc.contributor.authorGao, YTen_HK
dc.contributor.authorLu, Wen_HK
dc.contributor.authorZheng, Wen_HK
dc.date.accessioned2010-10-31T12:42:36Z-
dc.date.available2010-10-31T12:42:36Z-
dc.date.issued2010en_HK
dc.identifier.citationPlos Genetics, 2010, v. 6 n. 6, p. e1001002en_HK
dc.identifier.issn1553-7404en_HK
dc.identifier.urihttp://hdl.handle.net/10722/126685-
dc.description.abstractGenetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20-1.31) per allele (P = 3.2 x 10(-25)) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR = 1.19, 95% CI = 1.09-1.31, P = 1.3 x 10(-4), 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures.en_HK
dc.languageengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/-
dc.relation.ispartofPLoS Geneticsen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAsian Continental Ancestry Group - genetics-
dc.subject.meshBreast Neoplasms - etiology - genetics - pathology-
dc.subject.meshCell Line-
dc.subject.meshChromosomes, Human, Pair 16-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.titleIdentification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium.en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1553-7390&volume=6&issue=6, article no. e1001002&spage=&epage=&date=2010&atitle=Identification+of+a+functional+genetic+variant+at+16q12.1+for+breast+cancer+risk:+results+from+the+Asia+Breast+Cancer+Consortium-
dc.identifier.emailKhoo, US: uskhoo@hku.hken_HK
dc.identifier.emailChan, KY: kelvinc@pathology.hku.hken_HK
dc.identifier.authorityKhoo, US=rp00362en_HK
dc.identifier.authorityChan, KY=rp00453en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pgen.1001002en_HK
dc.identifier.pmid20585626-
dc.identifier.pmcidPMC2891809-
dc.identifier.scopuseid_2-s2.0-77954153479en_HK
dc.identifier.hkuros174291en_HK
dc.identifier.volume6en_HK
dc.identifier.issue6en_HK
dc.identifier.spagee1001002en_HK
dc.identifier.epagee1001002en_HK
dc.identifier.isiWOS:000279805200031-
dc.identifier.scopusauthoridLong, J=7403446542en_HK
dc.identifier.scopusauthoridCai, Q=7201853606en_HK
dc.identifier.scopusauthoridShu, XO=7102525083en_HK
dc.identifier.scopusauthoridQu, S=7202361951en_HK
dc.identifier.scopusauthoridLi, C=36548288000en_HK
dc.identifier.scopusauthoridZheng, Y=7404838014en_HK
dc.identifier.scopusauthoridGu, K=16052684300en_HK
dc.identifier.scopusauthoridWang, W=36549853400en_HK
dc.identifier.scopusauthoridXiang, YB=7201979437en_HK
dc.identifier.scopusauthoridCheng, J=8059167400en_HK
dc.identifier.scopusauthoridChen, K=35323979500en_HK
dc.identifier.scopusauthoridZhang, L=36549703800en_HK
dc.identifier.scopusauthoridZheng, H=35106399200en_HK
dc.identifier.scopusauthoridShen, CY=7402860075en_HK
dc.identifier.scopusauthoridHuang, CS=34768385900en_HK
dc.identifier.scopusauthoridHou, MF=7201437333en_HK
dc.identifier.scopusauthoridShen, H=7404522651en_HK
dc.identifier.scopusauthoridHu, Z=8392216300en_HK
dc.identifier.scopusauthoridWang, F=35197274600en_HK
dc.identifier.scopusauthoridDeming, SL=18436700500en_HK
dc.identifier.scopusauthoridKelley, MC=7403230316en_HK
dc.identifier.scopusauthoridShrubsole, MJ=6505816308en_HK
dc.identifier.scopusauthoridKhoo, US=7004195799en_HK
dc.identifier.scopusauthoridChan, KY=7406034195en_HK
dc.identifier.scopusauthoridChan, SY=36466096800en_HK
dc.identifier.scopusauthoridHaiman, CA=6701722861en_HK
dc.identifier.scopusauthoridHenderson, BE=36045477600en_HK
dc.identifier.scopusauthoridle Marchand, L=7006229986en_HK
dc.identifier.scopusauthoridIwasaki, M=9233646600en_HK
dc.identifier.scopusauthoridKasuga, Y=7006628725en_HK
dc.identifier.scopusauthoridTsugane, S=7005204049en_HK
dc.identifier.scopusauthoridMatsuo, K=7401602814en_HK
dc.identifier.scopusauthoridTajima, K=35374000300en_HK
dc.identifier.scopusauthoridIwata, H=7401885643en_HK
dc.identifier.scopusauthoridHuang, B=16743778400en_HK
dc.identifier.scopusauthoridShi, J=55491830200en_HK
dc.identifier.scopusauthoridLi, G=36548253300en_HK
dc.identifier.scopusauthoridWen, W=7102171018en_HK
dc.identifier.scopusauthoridGao, YT=34770682500en_HK
dc.identifier.scopusauthoridLu, W=55258833800en_HK
dc.identifier.scopusauthoridZheng, W=35381589100en_HK

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