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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
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TitleFunctional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women
 
AuthorsChan, KYK2
Liu, W2 6
Long, JR3
Yip, SP5
Chan, SY2 2
Shu, XO3
Chua, DTT2
Cheung, ANY2
Ching, JCY2
Cai, H3
Au, GKH2
Chan, M1
Foo, W4
Ngan, HYS2
Gao, YT7
Ngan, ESW2
GarciaBarceló, MM2
Zheng, W3
Khoo, US2
 
Issue Date2009
 
PublisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/
 
CitationJournal Of Medical Genetics, 2009, v. 46 n. 1, p. 32-39 [How to Cite?]
DOI: http://dx.doi.org/10.1136/jmg.2007.057174
 
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.
 
ISSN0022-2593
2012 Impact Factor: 5.703
2012 SCImago Journal Rankings: 2.715
 
DOIhttp://dx.doi.org/10.1136/jmg.2007.057174
 
PubMed Central IDPMC2782922
 
ISI Accession Number IDWOS:000262198000005
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.

 
ReferencesReferences in Scopus
 
GrantsGene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility
 
DC FieldValue
dc.contributor.authorChan, KYK
 
dc.contributor.authorLiu, W
 
dc.contributor.authorLong, JR
 
dc.contributor.authorYip, SP
 
dc.contributor.authorChan, SY
 
dc.contributor.authorShu, XO
 
dc.contributor.authorChua, DTT
 
dc.contributor.authorCheung, ANY
 
dc.contributor.authorChing, JCY
 
dc.contributor.authorCai, H
 
dc.contributor.authorAu, GKH
 
dc.contributor.authorChan, M
 
dc.contributor.authorFoo, W
 
dc.contributor.authorNgan, HYS
 
dc.contributor.authorGao, YT
 
dc.contributor.authorNgan, ESW
 
dc.contributor.authorGarciaBarceló, MM
 
dc.contributor.authorZheng, W
 
dc.contributor.authorKhoo, US
 
dc.date.accessioned2010-05-31T03:33:17Z
 
dc.date.available2010-05-31T03:33:17Z
 
dc.date.issued2009
 
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.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationJournal Of Medical Genetics, 2009, v. 46 n. 1, p. 32-39 [How to Cite?]
DOI: http://dx.doi.org/10.1136/jmg.2007.057174
 
dc.identifier.doihttp://dx.doi.org/10.1136/jmg.2007.057174
 
dc.identifier.eissn1468-6244
 
dc.identifier.epage39
 
dc.identifier.hkuros166040
 
dc.identifier.isiWOS:000262198000005
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.

 
dc.identifier.issn0022-2593
2012 Impact Factor: 5.703
2012 SCImago Journal Rankings: 2.715
 
dc.identifier.issue1
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC2782922
 
dc.identifier.pmid18782836
 
dc.identifier.scopuseid_2-s2.0-58549086564
 
dc.identifier.spage32
 
dc.identifier.urihttp://hdl.handle.net/10722/58601
 
dc.identifier.volume46
 
dc.languageeng
 
dc.publisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofJournal of Medical Genetics
 
dc.relation.projectGene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
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 women
 
dc.typeArticle
 
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<contributor.author>Long, JR</contributor.author>
<contributor.author>Yip, SP</contributor.author>
<contributor.author>Chan, SY</contributor.author>
<contributor.author>Shu, XO</contributor.author>
<contributor.author>Chua, DTT</contributor.author>
<contributor.author>Cheung, ANY</contributor.author>
<contributor.author>Ching, JCY</contributor.author>
<contributor.author>Cai, H</contributor.author>
<contributor.author>Au, GKH</contributor.author>
<contributor.author>Chan, M</contributor.author>
<contributor.author>Foo, W</contributor.author>
<contributor.author>Ngan, HYS</contributor.author>
<contributor.author>Gao, YT</contributor.author>
<contributor.author>Ngan, ESW</contributor.author>
<contributor.author>GarciaBarcel&#243;, MM</contributor.author>
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<description.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&#8594;C (rs799908:T&#8594;C), c.-2265C&#8594;T (rs11655505:C&#8594;T), c.-2004A&#8594;G (rs799906:A&#8594;G) and c.-1896(ACA) 1&#8594;(ACA) 2 (rs8176071:(ACA) 1&#8594;(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 &gt;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 &#8805;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 &#8805;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&#8594;T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.</description.abstract>
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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