Article: Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women
File Download
Links for fulltext
(May Require Subscription)
(May Require Subscription)
- Publisher Website: 10.1136/jmg.2007.057174
- Scopus: eid_2-s2.0-58549086564
- PMID: 18782836
- Find via
Supplementary
-
Citations:
| Title | Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Authors | Chan, KYK3 Liu, W3 6 Long, JR2 Yip, SP5 Chan, SY3 Shu, XO2 Chua, DTT3 Cheung, ANY3 Ching, JCY3 Cai, H2 Au, GKH3 Chan, M1 Foo, W4 Ngan, HYS3 Gao, YT7 Ngan, ESW3 GarciaBarceló, MM3 Zheng, W2 Khoo, US3 | ||||||||
| Issue Date | 2009 | ||||||||
| Publisher | BMJ 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?] DOI: http://dx.doi.org/10.1136/jmg.2007.057174 | ||||||||
| 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. | ||||||||
| ISSN | 0022-2593 2011 Impact Factor: 6.365 2011 SCImago Journal Rankings: 0.841 | ||||||||
| DOI | http://dx.doi.org/10.1136/jmg.2007.057174 | ||||||||
| ISI Accession Number ID | WOS:000262198000005
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. | ||||||||
| PubMed Central ID | PMC2782922 | ||||||||
| References | References in Scopus | ||||||||
| Grants | Identification of transcriptional factors interacting with the BRCA1 promoter Gene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility Gene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility |
| dc.contributor.author | Chan, KYK | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Liu, W | ||||||||
| dc.contributor.author | Long, JR | ||||||||
| dc.contributor.author | Yip, SP | ||||||||
| dc.contributor.author | Chan, SY | ||||||||
| dc.contributor.author | Shu, XO | ||||||||
| dc.contributor.author | Chua, DTT | ||||||||
| dc.contributor.author | Cheung, ANY | ||||||||
| dc.contributor.author | Ching, JCY | ||||||||
| dc.contributor.author | Cai, H | ||||||||
| dc.contributor.author | Au, GKH | ||||||||
| dc.contributor.author | Chan, M | ||||||||
| dc.contributor.author | Foo, W | ||||||||
| dc.contributor.author | Ngan, HYS | ||||||||
| dc.contributor.author | Gao, YT | ||||||||
| dc.contributor.author | Ngan, ESW | ||||||||
| dc.contributor.author | GarciaBarceló, MM | ||||||||
| dc.contributor.author | Zheng, W | ||||||||
| dc.contributor.author | Khoo, US | ||||||||
| dc.date.accessioned | 2010-05-31T03:33:17Z | ||||||||
| dc.date.available | 2010-05-31T03:33:17Z | ||||||||
| dc.date.issued | 2009 | ||||||||
| dc.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→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.grant | Identification of transcriptional factors interacting with the BRCA1 promoter | ||||||||
| dc.description.grant | Gene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility | ||||||||
| dc.description.grant | Gene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility | ||||||||
| dc.description.grantcode | 97870 | ||||||||
| dc.description.grantcode | 29671 | ||||||||
| dc.description.grantcode | 28077 | ||||||||
| dc.description.nature | published_or_final_version | ||||||||
| dc.identifier.citation | Journal 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.doi | http://dx.doi.org/10.1136/jmg.2007.057174 | ||||||||
| dc.identifier.epage | 39 | ||||||||
| dc.identifier.hkuros | 166040 | ||||||||
| dc.identifier.isi | WOS:000262198000005
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.issn | 0022-2593 2011 Impact Factor: 6.365 2011 SCImago Journal Rankings: 0.841 | ||||||||
| dc.identifier.issue | 1 | ||||||||
| dc.identifier.openurl | | ||||||||
| dc.identifier.pmcid | PMC2782922 | ||||||||
| dc.identifier.pmid | 18782836 | ||||||||
| dc.identifier.scopus | eid_2-s2.0-58549086564 | ||||||||
| dc.identifier.spage | 32 | ||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/58601 | ||||||||
| dc.identifier.volume | 46 | ||||||||
| dc.language | eng | ||||||||
| dc.publisher | BMJ Group. The Journal's web site is located at http://jmg.bmj.com/ | ||||||||
| dc.publisher.place | United Kingdom | ||||||||
| dc.relation.ispartof | Journal of Medical Genetics | ||||||||
| dc.relation.references | References in Scopus | ||||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||||
| dc.subject.mesh | BRCA1 Protein - genetics | ||||||||
| dc.subject.mesh | Breast Neoplasms - epidemiology - genetics | ||||||||
| dc.subject.mesh | Polymorphism, Genetic - genetics | ||||||||
| dc.subject.mesh | Promoter Regions, Genetic - genetics | ||||||||
| dc.subject.mesh | Transcription, Genetic | ||||||||
| dc.title | Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women | ||||||||
| dc.type | Article |
Author Affiliations
- Kwong Wah Hospital
- Vanderbilt Ingram Cancer Center
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- Queen Elizabeth Hospital Hong Kong
- Hong Kong Polytechnic University
- Soochow University
- null