Various carcinogenic metabolites, including catechol estrogens, play a role in malignant transformation. An enzyme that is capable of neutralizing the genotoxic effects of these compounds is catechol-O-methyltransferase (COMT). A variant form of this enzyme has been shown to reduce its activity by up to 4-fold; thus, we hypothesize that single nucleotide polymorphisms of the COMT gene can be a risk factor for benign prostatic hyperplasia (BPH) and prostate cancer. To test this hypothesis, the genetic distribution of three different COMT polymorphisms at codon 62 (C→T), codon 72 (G→T), and codon 158 (G→A) were analyzed in 131 normal healthy subjects, 134 BPH, and 178 sporadic prostate cancer samples from a Japanese population. Results of these experiments show that the variant genotype at codon 62 (P = 0.060) and codon 158 (P = 0.047) are risk factors for prostate cancer but not BPH when compared with normal controls. Odds ratio (OR) and 95% confidence interval (95% CI) for cancer were 3.24 and 1.38 to 7.61, respectively, for codon 62 T/T genotype when compared with wild type. At codon 158, the A/A variant for cancer had an OR of 3.00 with a 95% CI of 1.38 to 6.54 compared with wild type. Codons 62 and 158 were in linkage disequilibrium (LD), and when compared with the C-G haplotype, other types (C-A, T-G, T-A) were observed to be associated with prostate cancer (P = 0.040) but not BPH. Codon 72 on the other hand, was not in LD with either codon 62 or 158. The homozygous variant on codon 72 was rare in this Japanese population, and the heterozygous G/T at this codon was not associated with either prostate cancer or BPH. When evaluating the risk of COMT polymorphisms with stage or grade of cancer, no associations were observed for any of the genotypes with the exception of a tendency (P = 0.096) for the variant A allele on codon 158 to be correlated with higher stages (≥T₃) of cancer. This is the first report that shows the polymorphisms of COMT to be associated with sporadic prostatic carcinogenesis. These results are important in understanding the role of COMT polymorphisms in the pathogenesis of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(2):238–44)

We report the difference in quality of life (QOL) between patients with an orthotopic neobladder and normative values in the age matched Japanese population. Between November 1996 and June 2003, 75 patients underwent orthotopic neobladder construction at our institution, of whom 47 males and 9 females were enrolled in this study. A total of 19 patients were excluded because of death or insufficient followup (less than 6 months). Two types of questionnaire, namely the RAND 36-Item Health Survey, version 2 and the Functional Assessment of Cancer Therapy-Bladder Cancer, were mailed to all 56 patients. The 48 patients (86%) who returned the completed forms were included in our analysis. Postoperative QOL was compared with age matched normative values in the control Japanese population. Overall there was no significant difference in any scale between patients with a neobladder and the age matched control Japanese population. The patient bodily pain score in the seventh decade of life and the role-physical score in those older than 70 years were better than age matched normative values in the Japanese population (p <0.005 and p <0.05, respectively). Male patients in the seventh decade of life were more likely to have better QOL in the physical functioning, role-physical and role-emotional subscales in addition to the bodily pain subscale compared to age matched control values (p <0.05, <0.05, <0.001 and <0.001, respectively). Likewise in male patients older than 70 years role-physical scores remained better than age matched normative values in the Japanese population (p <0.01). Further analysis of bladder cancer related QOL showed that patients followed more than 24 months were more likely to have a lower incontinence score than those followed less than 24 months (p <0.05). In addition, the continence related QOL change alone did not affect any health related QOL scales, as analyzed by RAND 36-Intem Health Survey. Our study shows that there is no essential difference in health related QOL between patients with a neobladder and the age matched Japanese control population. The current results provide some primary evidence to help in decision making and eliminate potential anxiety about worse QOL after cystectomy.