The BRCA1 mutation c.5266dupC was originally described as a founder mutation in the Ashkenazi Jewish (AJ) population. However, this mutation is also present at appreciable frequency in several European countries, which raises intriguing questions about the origins of the mutation. We genotyped 245 carrier families from 14 different population groups (Russian, Latvian, Ukrainian, Czech, Slovak, Polish, Danish, Dutch, French, German, Italian, Greek, Brazilian and AJ) for seven microsatellite markers and confirmed that all mutation carriers share a common haplotype from a single founder individual. Using a maximum likelihood method that allows for both recombination and mutational events of marker loci, we estimated that the mutation arose some 1800 years ago in either Scandinavia or what is now northern Russia and subsequently spread to the various populations we genotyped during the following centuries, including the AJ population. Age estimates and the molecular evolution profile of the most common linked haplotype in the carrier populations studied further suggest that c.5266dupC likely entered the AJ gene pool in Poland approximately 400-500 years ago. Our results illustrate that (1) BRCA1 c.5266dupC originated from a single common ancestor and was a common European mutation long before becoming an AJ founder mutation and (2) the mutation is likely present in many additional European countries where genetic screening of BRCA1 may not yet be common practice.
Current evidence supporting probiotic use as adjunctive therapy to anticancer treatment is limited, especially in cancer patients treated with chemotherapy. Well designed clinical trials are needed to find true role of probiotics in oncology.
Febrile neutropenia (FN) remains a potentially life-threatening complication of anticancer chemotherapy. Bacterial translocation via intestinal mucosa is a significant mechanism of FN development. Competitive inhibition of bowel colonization by pathogenic microorganisms by lactic acid bacteria could be a useful prevention of FN. The aim of the study was the prevention of FN by probiotic strain Enterococcus faecium M-74 enriched with selenium in leukemic patients. Fourteen (six males/eight females) patients with myelogenous leukemia treated by induction or consolidation chemotherapy were included in the study. Patients received prophylaxis with E. faecium M-74 during one cycle of chemotherapy. The daily dose was 36 x 10(9) CFU tid. Prophylaxis started between day -2 and day +2 of chemotherapy and continued until the absolute neutrophile count (ANC) was >1,000/microl. All patients experienced febrile neutropenia. During 231 days of severe neutropenia, 30 febrile episodes occurred. No any febrile episode or infection provoked by the strain tested was noticed. Tolerance of therapy was excellent without significant adverse effects. Our results demonstrate the safety of the probiotic strain E. faecium M-74 enriched with selenium in leukemic patients with severe neutropenia. However, its administration was not effective in the prevention of febrile neutropenia, but this does not preclude the protective effect of other probiotic strains.
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