Novel germline MLH1 and MSH2 mutations in latvian Lynch syndrome families

Background/Aims: Hereditary non-polyposis colorectal cancer or Lynch syndrome is an autosomal dominantly inherited disease with high penetrance, mostly due to mutations in the MLH1 and MSH2 genes. The aim of this study is to investigate the mutation spectrum of the MLH1 and MSH2 genes. Methodology: High risk colorectal cancer families were selected from overall 1053 consecutive patients. Screening of germline mutations in the MLH1 and MSH2 was performed by direct sequencing and multiplex ligation-dependent probe amplification. Results: Ten patients fulfilled the Amsterdam I/II criteria and Bethesda guidelines of the Lynch syndrome. Three novel mutations were identified in MLH1 and MSH2 genes, as well as two known mutations in the MLH1 gene. Large rearrangements in the MLH1 gene were found in two patients. Conclusions: The mutations in the MLH1 and MSH2 genes in Latvian high-risk families are highly heterogeneous. Combination of direct sequencing and MLPA is the most appropriate molecular method of detecting hereditary nonpolyposis colorectal cancer patients and family members at risk

Evaluation of family histories and analysis of BRCA1 founder mutations in a population-based series of breast and ovarian cancer cases in Latvia

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Survival rates of familial and sporadic prostate cancer patients

Aim: To compare cancer-specific survival rates for familial and sporadic prostate cancer patients. Materials and Methods: Gleason score and age at diagnosis of familial group and sporadic group were compared by χ² and t-test. Cancer-specific survival rates were analyzed by the Kaplan — Meier method and compared by log-rank test. Statistically significant level was set at p < 0.05. Results: Among 1175 prostate cancer patients, familial group consisted of 215 (18.3%) patients, the sporadic group consisted of 960 (81.7%) patients. The familial group patient’s mean age at diagnosis (58.9 years old, 95% confidence interval (CI) 57.8–60.1) was significantly younger than that of sporadic group patients (67.2 years old, 95% CI 66.7–67.6) (p < 0.0001). Comparing Gleason score between familial group and sporadic group revealed no statistically significant difference. The analysis showed that 92% (95% CI 0.88–0.97) of familial group patients had a 10-year cancer-specific survival rates, which was a significantly better outcome than that of sporadic group with 69% (95% CI 0.60–0.78) 10-year cancer-specific survival rates (p = 0.0237). Conclusion: The study data demonstrate statistically significant difference between familial group and sporadic group concerning age and cancer-specific survival rates, but not Gleason score. Key Words: prostate cancer, hereditary, familial, survival rates

Impact of KRAS variant rs61764370 on breast cancer morbidity

Low-penetrance gene variants and their combinations are topical study objects in breast cancer pathogenesis. Single nucleotide polymorphism rs61764370, localized in 3՛ UTR of KRAS gene, plays an important role in the development and progression of seve­ral cancers. The aim of our study was to determine the KRAS variant impact on breast cancer morbidity. Patients and Methods: 2214 patients diagnosed with breast cancer and 861 healthy controls were screened for KRAS variant by RFLP method. Available clinical data were collected and processed using statistical analysis methods. Results of present study suggest the KRAS variant impact on breast cancer development risk in premenopausal women, but it has no effect on breast cancer prognosis. We did not observe any KRAS variant effect on breast cancer patient 10-year disease-specific survival rates. Key Words: breast cancer, rs61764370, KRAS variant, predisposing factor

Dissemination of a carbapenem-resistant acinetobacter baumannii strain belonging to international clone II/sequence type 2 and harboring a novel abar4-like resistance Island in Latvia

An outbreak of hospital-acquired Acinetobacter baumannii infections, caused by a blaOXA-23-positive carbapenem-resistant strain belonging to international clone II/ST2, was detected in Latvia. The strain was partially equipped with the armA gene and the intI1-aacA4-catB8-aadA1-qacE=1 class 1 integron. In addition, the strain carried AbaR25, a novel AbaR4-like resistance island of̃46,500 bp containing structures similar to the previously described AbaR22 and Tn6167 islands. AbaR25 was characterized by the occurrence of a second copy of Tn6022a interrupted by Tn2006 carrying the blaOXA-23 gene.publishersversionPeer reviewe

A Field Guide to Pandemic, Epidemic and Sporadic Clones of Methicillin-Resistant Staphylococcus aureus

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) have become a truly global challenge. In addition to the long-known healthcare-associated clones, novel strains have also emerged outside of the hospital settings, in the community as well as in livestock. The emergence and spread of virulent clones expressing Panton-Valentine leukocidin (PVL) is an additional cause for concern. In order to provide an overview of pandemic, epidemic and sporadic strains, more than 3,000 clinical and veterinary isolates of MRSA mainly from Germany, the United Kingdom, Ireland, France, Malta, Abu Dhabi, Hong Kong, Australia, Trinidad & Tobago as well as some reference strains from the United States have been genotyped by DNA microarray analysis. This technique allowed the assignment of the MRSA isolates to 34 distinct lineages which can be clearly defined based on non-mobile genes. The results were in accordance with data from multilocus sequence typing. More than 100 different strains were distinguished based on affiliation to these lineages, SCCmec type and the presence or absence of PVL. These strains are described here mainly with regard to clinically relevant antimicrobial resistance- and virulence-associated markers, but also in relation to epidemiology and geographic distribution. The findings of the study show a high level of biodiversity among MRSA, especially among strains harbouring SCCmec IV and V elements. The data also indicate a high rate of genetic recombination in MRSA involving SCC elements, bacteriophages or other mobile genetic elements and large-scale chromosomal replacements

A Field Guide to Pandemic, Epidemic and Sporadic Clones of Methicillin-Resistant Staphylococcus aureus

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) have become a truly global challenge. In addition to the long-known healthcare-associated clones, novel strains have also emerged outside of the hospital settings, in the community as well as in livestock. The emergence and spread of virulent clones expressing Panton-Valentine leukocidin (PVL) is an additional cause for concern. In order to provide an overview of pandemic, epidemic and sporadic strains, more than 3,000 clinical and veterinary isolates of MRSA mainly from Germany, the United Kingdom, Ireland, France, Malta, Abu Dhabi, Hong Kong, Australia, Trinidad & Tobago as well as some reference strains from the United States have been genotyped by DNA microarray analysis. This technique allowed the assignment of the MRSA isolates to 34 distinct lineages which can be clearly defined based on non-mobile genes. The results were in accordance with data from multilocus sequence typing. More than 100 different strains were distinguished based on affiliation to these lineages, SCCmec type and the presence or absence of PVL. These strains are described here mainly with regard to clinically relevant antimicrobial resistance- and virulence-associated markers, but also in relation to epidemiology and geographic distribution. The findings of the study show a high level of biodiversity among MRSA, especially among strains harbouring SCCmec IV and V elements. The data also indicate a high rate of genetic recombination in MRSA involving SCC elements, bacteriophages or other mobile genetic elements and large-scale chromosomal replacements