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Article: Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women

TitleFunctional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women
Authors
Issue Date2009
PublisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/
Citation
Journal Of Medical Genetics, 2009, v. 46 n. 1, p. 32-39 How to Cite?
Abstract
Background: The BRCA1 gene is an important breast-cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease. Methods and Results: Using direct sequencing of the BRCA1 promoter region, we identified four polymorphisms c.-2804T→C (rs799908:T→C), c.-2265C→T (rs11655505:C→T), c.-2004A→G (rs799906:A→G) and c.-1896(ACA) 1→(ACA) 2 (rs8176071:(ACA) 1→(ACA) 2) present in Hong Kong Chinese. Each polymorphism was studied independently and in combination by functional assays. Although all four variants significantly altered promoter activity, the c.-2265T allele had stronger binding than the C allele, and the most common mutant haplotype, which contains the c.-2265T allele, increased promoter activity by 70%. Risk association first tested in Hong Kong Chinese women with breast cancer and age-matched controls and replicated in a large population-based study of Shanghai Chinese, together totalling >3000 participants, showed that carriers of the c.-2265T allele had a reduced risk for breast cancer (combined odd ratio (OR) = 0.80, 95% Cl 0.69 to 0.93; p = 0.003) which was more evident among women aged ≥45 years at first diagnosis of breast cancer and without a family history of breast cancer (combined OR = 0.75, 95% Cl 0.61 to 0.91; p = 0.004). The most common haplotype containing the c.-2265T allele also showed significant risk association for women aged ≥45 years without a family history of breast cancer (OR = 0.64, 95% Cl 0.46 to 0.89; p = 0.008). Conclusion: This comprehensive study of BRCA1 promoter polymorphisms found four variants that altered promoter activity and with the most significant contribution from c.-2265C→T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.
Persistent Identifierhttp://hdl.handle.net/10722/58601
ISSN
2013 Impact Factor: 5.636
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council, Hong Kong SAR, ChinaHKU 7520/05M
University of Hong Kong200711159018
National Cancer InstituteRO1CA64277
RO1CA90899
Funding Information:

This study was funded by the Research Grant Council, Hong Kong SAR, China, (project code HKU 7520/05M) and the Committee on Research and Conference Grants from the University of Hong Kong (project code 200711159018). The Shanghai Breast Cancer Study is supported by RO1CA64277 and RO1CA90899 from the National Cancer Institute.

References
Grants

 

Author Affiliations
  1. Kwong Wah Hospital
  2. The University of Hong Kong Li Ka Shing Faculty of Medicine
  3. Vanderbilt Ingram Cancer Center
  4. Queen Elizabeth Hospital Hong Kong
  5. Hong Kong Polytechnic University
  6. Soochow University
  7. null
DC FieldValueLanguage
dc.contributor.authorChan, KYKen_HK
dc.contributor.authorLiu, Wen_HK
dc.contributor.authorLong, JRen_HK
dc.contributor.authorYip, SPen_HK
dc.contributor.authorChan, SYen_HK
dc.contributor.authorShu, XOen_HK
dc.contributor.authorChua, DTTen_HK
dc.contributor.authorCheung, ANYen_HK
dc.contributor.authorChing, JCYen_HK
dc.contributor.authorCai, Hen_HK
dc.contributor.authorAu, GKHen_HK
dc.contributor.authorChan, Men_HK
dc.contributor.authorFoo, Wen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorGao, YTen_HK
dc.contributor.authorNgan, ESWen_HK
dc.contributor.authorGarciaBarceló, MMen_HK
dc.contributor.authorZheng, Wen_HK
dc.contributor.authorKhoo, USen_HK
dc.date.accessioned2010-05-31T03:33:17Z-
dc.date.available2010-05-31T03:33:17Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Medical Genetics, 2009, v. 46 n. 1, p. 32-39en_HK
dc.identifier.issn0022-2593en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58601-
dc.description.abstractBackground: The BRCA1 gene is an important breast-cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease. Methods and Results: Using direct sequencing of the BRCA1 promoter region, we identified four polymorphisms c.-2804T→C (rs799908:T→C), c.-2265C→T (rs11655505:C→T), c.-2004A→G (rs799906:A→G) and c.-1896(ACA) 1→(ACA) 2 (rs8176071:(ACA) 1→(ACA) 2) present in Hong Kong Chinese. Each polymorphism was studied independently and in combination by functional assays. Although all four variants significantly altered promoter activity, the c.-2265T allele had stronger binding than the C allele, and the most common mutant haplotype, which contains the c.-2265T allele, increased promoter activity by 70%. Risk association first tested in Hong Kong Chinese women with breast cancer and age-matched controls and replicated in a large population-based study of Shanghai Chinese, together totalling >3000 participants, showed that carriers of the c.-2265T allele had a reduced risk for breast cancer (combined odd ratio (OR) = 0.80, 95% Cl 0.69 to 0.93; p = 0.003) which was more evident among women aged ≥45 years at first diagnosis of breast cancer and without a family history of breast cancer (combined OR = 0.75, 95% Cl 0.61 to 0.91; p = 0.004). The most common haplotype containing the c.-2265T allele also showed significant risk association for women aged ≥45 years without a family history of breast cancer (OR = 0.64, 95% Cl 0.46 to 0.89; p = 0.008). Conclusion: This comprehensive study of BRCA1 promoter polymorphisms found four variants that altered promoter activity and with the most significant contribution from c.-2265C→T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.en_HK
dc.languageengen_HK
dc.publisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/en_HK
dc.relation.ispartofJournal of Medical Geneticsen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong Licenseen_HK
dc.subject.meshBRCA1 Protein - genetics-
dc.subject.meshBreast Neoplasms - epidemiology - genetics-
dc.subject.meshPolymorphism, Genetic - genetics-
dc.subject.meshPromoter Regions, Genetic - genetics-
dc.subject.meshTranscription, Genetic-
dc.titleFunctional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese womenen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-2593&volume=46&spage=32&epage=39&date=2009&atitle=Functional+polymorphisms+in+the+BRCA1+promoter+influence+transcription+and+are+associated+with+decreased+risk+for+breast+cancer+in+Chinese+women.en_HK
dc.identifier.emailChan, KYK: kelvinc@pathology.hku.hken_HK
dc.identifier.emailChua, DTT: dttchua@hkucc.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailNgan, ESW: engan@hku.hken_HK
dc.identifier.emailGarciaBarceló, MM: mmgarcia@hku.hken_HK
dc.identifier.emailKhoo, US: uskhoo@hku.hken_HK
dc.identifier.authorityChan, KYK=rp00453en_HK
dc.identifier.authorityChua, DTT=rp00415en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityNgan, ESW=rp00422en_HK
dc.identifier.authorityGarciaBarceló, MM=rp00445en_HK
dc.identifier.authorityKhoo, US=rp00362en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1136/jmg.2007.057174en_HK
dc.identifier.pmid18782836en_HK
dc.identifier.pmcidPMC2782922-
dc.identifier.scopuseid_2-s2.0-58549086564en_HK
dc.identifier.hkuros166040en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58549086564&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume46en_HK
dc.identifier.issue1en_HK
dc.identifier.spage32en_HK
dc.identifier.epage39en_HK
dc.identifier.eissn1468-6244-
dc.identifier.isiWOS:000262198000005-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectGene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility-
dc.identifier.scopusauthoridChan, KYK=7406034195en_HK
dc.identifier.scopusauthoridLiu, W=36078432200en_HK
dc.identifier.scopusauthoridLong, JR=7403446542en_HK
dc.identifier.scopusauthoridYip, SP=7102133673en_HK
dc.identifier.scopusauthoridChan, SY=36466096800en_HK
dc.identifier.scopusauthoridShu, XO=7102525083en_HK
dc.identifier.scopusauthoridChua, DTT=7006773480en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK
dc.identifier.scopusauthoridChing, JCY=15735635300en_HK
dc.identifier.scopusauthoridCai, H=12802855000en_HK
dc.identifier.scopusauthoridAu, GKH=7003748615en_HK
dc.identifier.scopusauthoridChan, M=7402597760en_HK
dc.identifier.scopusauthoridFoo, W=7003318564en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridGao, YT=34770682500en_HK
dc.identifier.scopusauthoridNgan, ESW=22234827500en_HK
dc.identifier.scopusauthoridGarciaBarceló, MM=6701767303en_HK
dc.identifier.scopusauthoridZheng, W=35381589100en_HK
dc.identifier.scopusauthoridKhoo, US=7004195799en_HK

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