The aim of this study was to evaluate the prevalence of simple sequence variation in the BRCA2 gene. To this end, 71 breast and breast-ovarian cancer (HBC/HBOC) families along with 95 control individuals from a wide range of ethnicities were analyzed by means of denaturing high-performance liquid chromatography (DHPLC) and direct sequence analysis. In the coding (10 257 bp) and non-coding (2799 bp) sequences of BRCA2, 82 sequence variants were identified. Three different, apparently disease-associated BRCA2 mutations were found in six HBC/HBOC families (8%): two splice site mutations in introns 5 and 21, and one frameshift mutation in exon 11. In the coding region, 53 simple sequence variants were found: 35 missense mutations, one 2 bp deletion (CT) resulting in a stop at codon 3364, one nonsense mutation with a stop at codon 3326, one deletion of a complete codon (AAA) resulting in the loss of leucine, and 15 silent mutations. In the non-coding region, 26 polymorphisms were detected. Of the 79 sequence variants that were not obviously disease-associated, eight were detected only in HBC/HBOC families. The remaining 71 variants were identified in both HBC/HBOC families and control individuals. Sixty three sequence variants (80%) were specific for a continent. Forty two percent (33 out of 79) of the sequence variants were detected exclusively in Africa, though only 13% of the 332 chromosomes screened were of African origin. Our data indicate that, in BRCA2, simple sequence variation is frequent [in the coding region 1 in 194 bp (straight theta = 2.2 x 10(-4)), and in the non-coding region 1 in 108 bp (straight theta = 4.4 x 10(-4)), respectively].

Introduction: Our aim was to identify the independent risk factors associated with urinary incontinence after radical retropubic prostatectomy (RRP). Materials and Methods: Using univariate and multivariate analyses, we examined several pre- and perioperative factors. One hundred and sixty-six patients were divided into three groups: patients who were immediately continent after catheter removal (group I), patients who became continent later (group II) and incontinent patients (group III). Results: There were 34 patients (20.5%) in group I, 111 (66.9%) in group II, and 21 (12.6%) in group III. The multivariate analysis between the continent and incontinent patients proved that the postoperatively measured total length of the posterior urethra (strongly associated with length of the sphincter, length of the urethral stump and the presence of anastomotic stricture) was the independent risk factor for permanent incontinence or delayed continence following RRP. The age of patients per se represented a risk factor only for delayed continence, but not for permanent incontinence. Conclusions: Postoperatively measured shorter posterior urethral length results in an increased risk of urinary incontinence and delays continence after RRP. It seems that older age only delays reaching continence.

Fulvestrant appears to be an efficient and well-tolerated drug even in women with advanced breast cancer progressing after multiple endocrine and/or cytotoxic treatments.

MAC-321 can be safely administered orally once every 21 days up to a dose of 60 mg/m(2). The major DLT was neutropenic fever. Four subjects had disease stabilization.

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