Plakhins G., Irmejs A., Gardovskis A., Subatniece S., Rozite S., Bitina M., Keire G., Purkalne G., Teibe U., Trofimovics G., Miklasevics E., Gardovskis J. Genotype/phenotype correlations among BRCA1 4153delA and 5382insC mutation carriers from Latvia. BMC Medical Genetics, 2011, 12:147.
http://www.biomedcentral.com/1471-2350/12/147
Kopsavilkums
Mutations 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.
We 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.
We 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.
Our 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.
Abele A., Vjaters E., Irmejs A., Trofimovičs G., Miklaševičs E., Gardovskis J. Epidemiological, clinical and molecular characteristics of hereditary prostate cancer in Latvia. Medicina (Kaunas), 2011, accepted.
http://www.ncbi.nlm.nih.gov/pubmed/22186123
Kopsavilkums
Prostate cancer is one of the most commonly diagnosed malignancy affecting men in Latvia. The aim of this study was to evaluate the epidemiological features and molecular basis of hereditary prostate cancer in Latvia. A total of 1217 newly diagnosed prostate cancer patients were recruited in our study. Data were analyzed according to clinical diagnostic criteria for hereditary prostate cancer. Molecular testing for the founder mutation 657del5 of the NBS1 gene was performed for the first 280 prostate cancer patients and 173 control cases, and for the founder mutations 300T/G, 4153delA, and 5382insC of the BRCA1 gene for 112 prostate cancer patients with a history of breast or ovarian cancer in their families. Of the 1217 families, 14 (1.2%; 95% CI, 0.7%-1.9%) matched clinical diagnostic criteria for definitive hereditary prostate cancer, and of the 1217 families, 196 (16.1%; 95% CI, 14.1%-18.3%) for suspected hereditary prostate cancer. The founder mutation of the NBS1 gene was detected in 1 (0.4%, 95% CI, 0.1%-2.0%) of the 280 cases in the prostate cancer group and in 1 (0.6%; 95% CI, 0.1%-3.2%) of the 173 cases in the control group. The mutation 5382insC of the BRCA1 gene was detected in 2 (1.8%; 95% CI, 0.5%-6.3%) of the 112 cases analyzed in the prostate cancer group. No other BRCA1 founder mutations were detected. Our study did not reveal predisposition genes for hereditary prostate cancer as the founder mutations of the BRCA1 and NBS1 genes are rarely detected in Latvia, but showed the importance of evaluation risk individually as a positive family history of cancer was associated with the earlier onset of prostate cancer.
