Germline mutations of BRCA1 and BRCA2 genes in Turkish breast, ovarian, and prostate cancer patients.

Distribution and prevalence of germline mutations in BRCA1 and BRCA2 differ among different populations. For the Turkish population, several studies have addressed high-risk breast cancer and ovarian cancer (BC-OC) patients. In most studies, both genes were analyzed in part, and a quite heterogeneous mutation spectrum was observed. For high-risk Turkish prostate cancer (PCa) patients, however, there are no data available about mutations of germline BRCA genes. To accurately determine the contribution of germline mutations in BRCA1 and BRCA2 in Turkish BC, OC, and PCa high-risk patients, 106 high-risk BC-OC patients, 50 high-risk PCa patients, and 50 control subjects were recruited. The study represents the only full screening, to date, of a large series of Turkish high-risk BC-OC patients and the only study in Turkish high-risk PCa patients. Mutation screenings were performed on coding exons of both genes with either denaturing gradient gel electrophoresis or denaturing high performance liquid chromatography, or with both techniques. Three deleterious mutations in BRCA1 and three deleterious mutations in BRCA2 were detected in different BC-OC patients, and one truncating mutation was detected in a high-risk PCa patient. In addition, 28 different unclassified and mostly novel variants were detected in both genes, as well as several silent polymorphisms. These findings reflect the genetic heterogeneity of the Turkish population and are relevant to genetic counseling and clinical management.

Comparing two ureter reimplantation techniques in kidney transplant recipients.

We compared the incidence of urological and anastomotic complications for the ureteroureterostomy and Lich-Gregoir techniques in kidney transplant recipients. Between May 2003 and February 2004, 75 kidney transplant recipients from living donors were divided into two similar groups to receive ureteroureterostomy (n = 41, 28 male, 13 female) and Lich-Gregoir techniques (n = 34, 24 male, 10 female) for ureteral reimplantation. Patients with vesicoureteral reflux (VUR) to the native kidneys were excluded from the study. The urological complications included complicated hematuria, ureteral stenosis, symptomatic VUR, recurrent urinary tract infection (UTI). There was no statistical significance between two groups in terms of gender, age, end-stage renal disease etiology, human leucocyte antigen (HLA) mismatch numbers, type and duration of dialysis, and cold ischemia time. The incidence of urologic and anastomotic complications was 12%. Complications in the Lich-Gregoir group included symptomatic VUR in 8.8% and stent migration in 2.9% of cases. Complications observed in the ureteroureterostomy group were ureteral stricture 7.3% and complicated hematuria in 4.9% of cases. However, symptomatic reflux was not observed in the ureteroureterostomy group. UTI frequency was similar in both groups. Ureteroureterostomy can be safely performed as a primary choice in kidney transplant recipients.

Effects of some hematological parameters on whole blood tacrolimus concentration measured by two immunoassay-based analytical methods.

OBJECTIVES: Tacrolimus (FK506) is a potent immunosuppressive drug used for prevention of rejection following transplantation. Several methods including immunoassays have been used for monitoring tacrolimus levels. The purpose of the present study was to compare the effects of various hematological parameters on whole blood tacrolimus concentrations which were measured with two different analytical methods, namely the microparticle enzyme immunoassay (MEIA II) and enzyme multiplied immunoassay technique (EMIT). DESIGN AND METHODS: The effects of hematological variables, namely hematocrit (Htc), hemoglobin (Hb), red blood cell (RBC), mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), red cell distribution width (RDW) and platelet (PLT) counts on tacrolimus concentrations (n = 2430 measurements) measured with EMIT (n = 1171) and MEIA II (n = 1259) methods in whole blood samples from kidney or liver or combined kidney-pancreas transplant patients (n = 162) during a 2-year post-transplantation period were compared. RESULTS: The whole blood tacrolimus concentrations measured with MEIA II method were affected much more significantly by hematological parameters than those measured with EMIT method. In MEIA II method, RDW (r = 0.479, P < 0.01) showed a stronger correlation with tacrolimus concentration than Htc (r = -0.239, P < 0.01) in all patients. A negative significant correlation (r = -0.468, P < 0.01) was also observed between the Htc and tacrolimus concentration in patients with Htc values < or =25% in MEIA II method. CONCLUSIONS: The results of the present study suggest that EMIT method might be preferred to MEIA II in determination of whole blood tacrolimus concentrations in anemic transplant patients. For better therapeutic drug monitoring, physicians should be aware of these assay differences. Evaluation of hematologic factors that affect the whole blood concentrations of tacrolimus may be helpful in deciding the dosage of this drug.

Germline mutations in the BRCA1 and BRCA2 genes in Turkish breast/ovarian cancer patients.

In this study we genotyped Turkish breast/ovarian cancer patients for BRCA1/BRCA2 mutations: protein truncation test (PTT) for exon 11 BRCA1 of and, multiplex PCR and denaturing gradient gel electrophoresis (DGGE) for BRCA2, complemented by DNA sequencing. In addition, a modified restriction assay was used for analysis of the predominant Jewish mutations: 185delAG, 5382InsC, Tyr978X (BRCA1) and 6174delT (BRCA2). Eighty three breast/ovarian cancer patients were screened: twenty three had a positive family history of breast/ovarian cancer, ten were males with breast cancer at any age, in eighteen the disease was diagnosed under 40 years of age, one patient had ovarian cancer in addition to breast cancer and one patient had ovarian cancer. All the rest (n=30) were considered sporadic breast cancer cases. Overall, 3 pathogenic mutations (3/53-5.7%) were detected, all in high risk individuals (3/23-13%): a novel (2990insA) and a previously described mutation (R1203X) in BRCA1, and a novel mutation (9255delT) in BRCA2. In addition, three missense mutations [two novel (T42S, N2742S) and a previously published one (S384F)] and two neutral polymorphisms (P9P, P2532P) were detected in BRCA2. Notably none of the male breast cancer patients harbored any mutation, and none of the tested individuals carried any of the Jewish mutations. Our findings suggest that there are no predominant mutations within exon 11 of the BRCA1 and in BRCA2 gene in Turkish high risk families.