Genotype-phenotype correlations among BRCA14153delA and 5382insC mutation carriers from Latvia

BMC Medical Genetics

Research Article

Marianna Bitina¹  Uldis Teibe²  Signe Subatniece³  Edvins Miklasevics³  Grigorijs Plakhins⁴  Genadijs Trofimovics⁵  Janis Gardovskis⁵  Arvids Irmejs⁵  Andris Gardovskis⁵  Guntars Keire⁶  Gunta Purkalne⁷  Santa Rozite⁸ 

[1] Department of Oncology, Daugavpils Regional Hospital, Vasarnicu Street 20, LV-5417, Daugavpils, Latvia;Department of Physics, Riga Stradins University, Dzirciema Street 16, LV-1007, Riga, Latvia;Hereditary Cancer Institute, Riga Stradins University, Dzirciema Street 16, LV-1007, Riga, Latvia;Hereditary Cancer Institute, Riga Stradins University, Dzirciema Street 16, LV-1007, Riga, Latvia;Oncology Clinic, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, LV-1002, Riga, Latvia;Hereditary Cancer Institute, Riga Stradins University, Dzirciema Street 16, LV-1007, Riga, Latvia;Surgery Clinic, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, LV-1002, Riga, Latvia;Oncology Clinic, Liepaja Piejuras Hospital, Jurmalas Street 2, LV-3401, Liepaja, Latvia;Oncology Clinic, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, LV-1002, Riga, Latvia;The Centre of Health Economics, Ministry of Health of the Republic of Latvia, Duntes Street 12/22, LV-1005, Riga, Latvia;

关键词: Ovarian Cancer;    Mutation Carrier;    BRCA1 Mutation;    Ovarian Cancer Patient;    Contralateral Breast Cancer;   

DOI  :  10.1186/1471-2350-12-147

 received in 2011-03-06, accepted in 2011-10-27,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundMutations in the high penetrance breast and ovarian cancer susceptibility gene BRCA1 account for a significant percentage of hereditary breast and ovarian cancer cases. Genotype-phenotype correlations of BRCA1 mutations located in different parts of the BRCA1 gene have been described previously; however, phenotypic differences of specific BRCA1 mutations have not yet been fully investigated. In our study, based on the analysis of a population-based series of unselected breast and ovarian cancer cases in Latvia, we show some aspects of the genotype-phenotype correlation among the BRCA1 c.4034delA (4153delA) and c.5266dupC (5382insC) founder mutation carriers.MethodsWe investigated the prevalence of the BRCA1 founder mutations c.4034delA and c.5266dupC in a population-based series of unselected breast (n = 2546) and ovarian (n = 795) cancer cases. Among the BRCA1 mutation carriers identified in this analysis we compared the overall survival, age at diagnosis and family histories of breast and ovarian cancers.ResultsWe have found that the prevalence of breast and ovarian cancer cases (breast: ovarian cancer ratio) differs significantly among the carriers of the c.5266dupC and c.4034delA founder mutations (OR = 2.98, 95%CI = 1.58 to 5.62, P < 0.001). We have also found a difference in the prevalence of breast and ovarian cancer cases among the 1st and 2nd degree relatives of the c.4034delA and c.5266dupC mutation carriers. In addition, among the breast cancer cases the c.4034delA mutation has been associated with a later age of onset and worse clinical outcomes in comparison with the c.5266dupC mutation.ConclusionsOur data suggest that the carriers of the c.4034delA and c.5266dupC founder mutations have different risks of breast and ovarian cancer development, different age of onset and prognosis of breast cancer.

【 授权许可】

CC BY   
© Plakhins et al; licensee BioMed Central Ltd. 2011