Glutathione S-transferase null genotypes in transitional cell bladder cancer: a case-control study.

OBJECTIVES: This study was conducted (1) to examine whether the GSTM1 and GSTT1 null genotypes are risk factors for bladder cancer, and (2) to study a possible association of these genotypes with disease severity. METHODS: This case-control study was undertaken over a 21-month period and included 89 newly diagnosed transitional cell bladder cancer patients and 147 controls; both patients and controls originated from a defined population (residents of the loannina region, Northwestern Greece) and were similar with regard to mean age, male to female ratio and smoking habits. The GSTM1 and GSTT1 genotypes were identified by multiplex polymerase chain reaction on peripheral blood DNA samples. Genotype frequencies among patients and controls were assessed and the association of the genotypes with tumor grade and stage at presentation were statistically evaluated by the chi(2) test. RESULTS: The GSTM1 null genotype was strongly associated with bladder cancer. The odds ratio, attributable and population attributable risks were estimated at 2.76, 0.64 and 0.40, respectively. The correlation between the GSTM1 null genotype with stage, although not statistically significant, was estimated at an odds ratio of 2.6 for invasive disease. The correlation of GSTM1 null genotype with tumor grade did not yield a statistically significant result. The GSTT1 null genotype was not statistically associated with bladder cancer. CONCLUSION: According to our study, individuals with the GSTM1 null genotype carry a substantially higher risk for bladder carcinogenesis. The GSTM1 null genotype is not associated with more aggressive disease in terms of tumor grade, although there is a correlation between this genotype and stage of the disease.

Genotypes of N-acetyltransferase-2 and risk of bladder cancer: a case-control study.

PURPOSE: This study was conducted to examine whether certain slow N-acetylation genotypes could be risk factors for bladder cancer, and the possible association between specific genotypes and the severity of the disease at first diagnosis. MATERIALS AND METHODS: This case-control study included 89 patients with transitional cell bladder cancer (diagnosed over a period of 21 months) and 147 controls. N-acetyltransferase-2 (NAT-2) genotypes were identified by allele specific polymerase chain reaction (PCR) on peripheral blood DNA samples. The x2 test was used for statistical evaluation to compare the differences observed between patients and controls and the different genotypes with tumor grading and local staging at presentation. Relative, attributable and population attributable risks were estimated for the genotypes found to present a significantly increased frequency for bladder cancer. RESULTS: A statistically significant difference in the frequency of genotypes was found between the two groups. The patient group had the higher frequency of slow acetylation genotypes (p = 0.0016). Among slow acetylators, homozygotes 341C/341C and compound heterozygotes 341C/857A had the most excessive risk for bladder cancer (p = 0.0041 and 0.0031, respectively). The 341C/341C genotype was found to be associated with more aggressive disease, in terms of tumor grading at presentation (p <0.05). CONCLUSIONS: According to our data, slow acetylators with 341C/341C and 341C/857A genotypes carry a substantially higher odds ratio (3.73 and 12.46, respectively) for bladder carcinogenesis. Additionally, among the slow acetylators, 341C/341C homozygotes are likely to have a higher risk for more aggressive disease.

Infertility and multiple urogenital abnormalities in a male with mosaic 46,XY/45,XO/47,XXY karyotype and mixed phenotype.

We hereby present a rare case of a 46,XY/45,XO/47,XXY mosaic male patient with a predominance of the XY cell line. The patient, who exhibited phenotypic stigmata of both XO gonadal dysgenesis and Klinefelter syndromes, suffered from infertility and multiple urogenital abnormalities, as our investigation revealed.