Recent studies have demonstrated that heterozygous carriers of the NBS1 657del5 mutation have an increased risk for familial and bilateral breast cancer, but similar studies in consecutive breast cancer patients were inconclusive. Here, in a study of 562 nonselected breast cancer patients from Central Poland, we found 11 (1.96%) 657del5 mutation carriers vs. 3.47 expected (OR 3.21, 95%CI: 1.36-7.61, p 5 0.0107) and only 9 (1.6%) carriers of the 5382insC mutation of the BRCA1 gene, most frequently found among breast cancer patients in Poland. No carriers of R215W, another pathogenic mutation of the NBS1 gene, were found in the present study. All carriers of the 657del5 mutation had sporadic breast tumors while 5 of 9 5382insC carriers had a family history of breast/ovarian cancer or bilateral breast carcinoma. In the pooled group of patients from the present and our previous study, carried out also in patients from Central Poland, we obtained the following risk estimates (OR) for 657del5 carriers, as related to the age at breast cancer diagnosis: <40 years: 8.36; (95%CI: 2.57-27.27) p 5 0.0003; <50 years: 4.27 (95%CI: 1.67-10.89) p 5 0.003; 50 years: 2.40 (95%CI: 0.91-6.35) p 5 0.1250; all ages: 3.13 (95% CI: 1.40-7.00) p 5 0.0066. These findings demonstrate conclusively that NBS1 657del5 mutation carriers have a significantly, though moderately increased, age-related risk of breast cancer, and imply that in populations with a high 657del5 carrier frequency this mutation may contribute substantially to the overall incidence of breast cancer, particularly in younger age groups. ' 2006 Wiley-Liss, Inc.

ObjectiveThe aim of the study was to investigate whether the Gln223Arg in the leptin receptor may influence body weight, leptin concentration, and metabolic parameters in children.Materials and methodsThe examined group included 101 obese children (58 girls and 43 boys) with BMI 31.41 ± 5.03 kg/m2 (BMI ≥ 2 SDS) and the control group consisted of 41 children with BMI 20.0 ± 0.80 kg/m2 (BMI < 1.0 SDS). Polymorphism identification was performed in total genomic DNA using PCRRFLP method.ResultsThe distribution of genotypes LEPR was the following: in the obese group: AA - 20.8%, AG-55.4%, GG-23.8%; in the control group AA-31.7%, AG-53.65%, GG-14.65%. Comparative analyses between AA homozygous children and carriers of G alleles did not confirm any relation between the analyzed polymorphism and BMI, leptin concentrations, and metabolic disturbances in children with obesity.ConclusionIn children with obesity we did not observe association of the LEPR Gln223Arg gene polymorphism with obesity, leptin, insulin resistance, and metabolic abnormalities.

We aimed to investigate the occurrence and types of pathogenic mutations in the RET gene in patients with MTC of the Central Poland population and in their relatives. DNA was extracted from the peripheral blood lymphocytes of a total of 330 persons, including 235 MTC patients and 95 of their unaffected kindred's. Exons 10, 11, 13, 14, 15 and 16 of the RET gene were amplified by PCR and sequenced. Sixty-seven people were found to carry pathogenic, germline mutations in the RET gene. In exon 10, C609F, C609R and C609Y (3 families), C618G, C618F (2 families), and C620G (4 families) mutations were identified. In exon 11, C634R (8 families) and C649L mutations (1 patient) were found. Five families carried Y791F mutation in exon 13. One patient with PTC revealed the presence of a Y791F mutation. In 3 families, exon 14 of the RET gene harbored the following mutations: V804L (1 patient), E819K (1 patient) and R844Q (1 patient). In 1 family, the S891A mutation was identified in exon 15, 3 families were found to carry mutations in exon16, R912P in 1 family and M918T in 2 families. In summary, of the 235 patients affected by MTC, 46 (19.6%) carried pathogenic RET gene mutations, 1 patient with RET mutation had kidney carcinoma, and 1 had PTC. The results show the occurrence of a variety of mutations prevalent in patients with MTC in the population of Central Poland. These results may contribute to a better diagnosis of medullary thyroid carcinoma.

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