Polymorphisms in the E-cadherin (CDH1) gene promoter and the risk of bladder cancer.

AIM: E-cadherin plays a role in carcinogenesis. For two genetic polymorphisms in the gene (CDH1) promoter, a reduced transcription has been reported: a C/A single nucleotide polymorphism (SNP) and a G/GA SNP at -160 bp and -347 bp, respectively, upstream of the transcriptional start site. We studied the association between both polymorphisms and the risk of bladder cancer. METHODS: One hundred and ninety-seven patients with bladder cancer and 344 population controls were genotyped and haplotyped for both SNPs. RESULTS: A borderline significantly increased risk for bladder cancer was found for A allele carriers (OR 1.36; 95% CI: 0.96-1.94). We did not find any association between the -347 G/GA SNP and bladder cancer. Haplotype analyses did not yield much stronger associations with bladder cancer than the -160 C/A genotype analyses. CONCLUSION: This study supports earlier suggestions that the -160 C/A SNP in the CDH1 promoter is a risk factor for bladder cancer.

Polymorphisms in the alpha1A-adrenoceptor gene do not modify the short- and long-term efficacy of alpha1-adrenoceptor antagonists in the treatment of benign prostatic hyperplasia.

OBJECTIVE To determine whether a common single nucleotide polymorphism (SNP) in the ADRA1A gene encoding the alpha(1A)-adrenoceptor modifies the short- and long-term efficacy of alpha(1)-adrenoceptor antagonists in the treatment of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS For 254 patients with BPH and/or lower urinary tract symptoms who received alpha(1)-adrenergic antagonists for > or = 3 months, the ADRA1A genotype at position 1475 of the coding region was determined. The patients' short-term response to treatment was determined for four outcome measures, i.e. the International Prostate Symptom Score (IPSS), the IPSS quality-of-life score, peak urinary flow rate, and obstruction grade, stratified by genotype. Eventual BPH-related invasive therapy was used as the outcome for assessing the long-term response to treatment. Genetic variants at positions 834, 896, 898 and 1831 were too rare to be considered in the analysis. RESULTS There were no significant differences for the genotype strata in three of the four outcome measures. Patients with the CC genotype responded significantly better in quality-of-life perception than patients with the CT or TT genotype. There were also no significant differences in the risk of BPH-related invasive therapy among the three genotypes. CONCLUSIONS The 1475C-->T SNP in the ADRA1A gene does not modify the short- and long-term efficacy of alpha(1)-adrenoceptor antagonists for treating BPH. There was a small effect on perceived quality of life but this was not reflected in other variables that measured the treatment response more directly.

Prevalence of von Hippel-Lindau gene mutations in sporadic renal cell carcinoma: results from The Netherlands cohort study.

BACKGROUND: Biallelic von Hippel-Lindau (VHL) gene defects, a rate-limiting event in the carcinogenesis, occur in approximately 75% of sporadic clear-cell Renal Cell Carcinoma (RCC). We studied the VHL mutation status in a large population-based case group. METHODS: Cases were identified within the Netherlands cohort study on diet and cancer, which includes 120,852 men and women. After 11.3 years of follow-up, 337 incident cases with histologically confirmed epithelial cancers were identified. DNA was isolated from paraffin material collected from 51 pathology laboratories and revised by one pathologist, leaving material from 235 cases. VHL mutational status was assessed by SSCP followed by direct sequencing, after testing SSCP as a screening tool in a subsample. RESULTS: The number of mutations was significantly higher for clear-cell RCC compared to other histological types. We observed 131 mutations in 114 out of 187 patients (61%) with clear-cell RCC. The majority of mutations were truncating mutations (47%). The mean tumor size was 72.7 mm for mutated tumors compared to 65.3 mm for wildtype tumors (p = 0.06). No statistically significant differences were observed for nuclear grade, TNM distribution or stage. In other histological types, we observed 8 mutations in 7 out of 48 patients (15%), 1 mutation in 1 of 6 oncocytoma, 3 mutations in 2 of 7 chromophobe RCC, 2 mutations in 2 of 30 papillary RCC, no mutations in 1 collecting duct carcinoma and 2 mutations in 2 of 4 unclassified RCC. CONCLUSION: VHL mutations were detected in 61% of sporadic clear-cell RCC. VHL mutated and wildtype clear-cell RCC did not differ with respect to most parameters.