Novel mutations in the BRCA1 and BRCA2 genes in Iranian women with early-onset breast cancer

Breast Cancer Research

Ann Dalton³  David P Hornby⁵  Mohammad A Mohagheghi¹  Soghra Jarvandi²  Iraj Harirchi²  Sirous Zeinali⁴  Vahid R Yassaee³ 

[1] Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran;Iranian Centre for Breast Cancer (ICBC), Tehran University of Medical Sciences, Tehran, Iran;North Trent Molecular Genetics Laboratory, Sheffield Children's Hospital, Sheffield, UK;Department of Molecular Biotechnology, Pasteur Institute, Tehran, Iran;Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, UK

关键词: mutation detection methods;    Iranian population;    breast cancer;    BRCA2;    BRCA1;   

Others  :  1118828
DOI  :  10.1186/bcr443

 received in 2001-11-02, accepted in 2002-03-12,  发布年份 2002

【 摘 要 】

Background

Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. So far, germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast and/or ovarian cancer have not been identified within the Iranian population.

Methods

With the collaboration of two main centres for cancer in Iran, we obtained clinical information, family history and peripheral blood from 83 women under the age of 45 with early-onset breast cancer for scanning of germline mutations in the BRCA1 and BRCA2 genes. We analysed BRCA1 exons 11 and BRCA2 exons 10 and 11 by the protein truncation test, and BRCA1 exons 2, 3, 5, 13 and 20 and BRCA2 exons 9, 17, 18 and 23 with the single-strand conformation polymorphism assay on genomic DNA amplified by polymerase chain reaction.

Results

Ten sequence variants were identified: five frameshifts (putative mutations – four novel); three missense changes of unknown significance and two polymorphisms, one seen commonly in both Iranian and British populations.

Conclusions

Identification of these novel mutations suggests that any given population should develop a mutation database for its programme of breast cancer screening. The pattern of mutations seen in the BRCA genes seems not to differ from other populations studied. Early-onset breast cancer (less than 45 years) and a limited family history is sufficient to justify mutation screening with a detection rate of over 25% in this group, whereas sporadic early-onset breast cancer (detection rate less than 5%) is unlikely to be cost-effective.

【 授权许可】

   
2002 Yassaee et al., licensee BioMed Central Ltd

【 图 表 】

Figure 2.

Figure 1.

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