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In a population-based study, disease progression and survival were evaluated in untreated patients with newly diagnosed cancer of the prostate without distant metastases. Complete follow-up was achieved in 223 of 227 (98%) consecutively diagnosed, eligible patients of all ages. After 5 years, the cumulative progression-free survival (with 95% confidence interval) was 71.8 (65.5-78.1)% and survival corrected for causes of death other than prostatic cancer was 93.8 (88.3-97.6)%. Univariate and multivariate analyses showed no association between age at diagnosis and the natural course. Local progression was less common in localised, non-palpable tumours than in larger tumours. The rate of progression was 18.7 (6.1-57.1) times higher and that of disease-specific death 216.0 (31.2-1496) times higher in patients with poorly than in those with highly differentiated tumours. It is concluded that tumour grade at diagnosis is an excellent predictor of local and distant progression. The low death rate, especially in patients with highly and moderately differentiated tumours, means that any local or systemic therapy intended for patients with early prostatic cancer must be evaluated in clinical trials with untreated controls for comparison.

Ten men with prostatic cancer, stage T3M0 Nx or more, who were anxious to maintain sexual potency, were treated with flutamide. The eight metastasis-free tumours remained stable during treatment periods of 3-48 months. The two tumours with metastasis at the start of treatment showed growth inhibition for 3 and 7 months, respectively, but thereafter progressed, leading to change of treatment. Nine of the ten men claimed maintained potency during flutamide therapy. Seven delivered ejaculate for biochemical analysis during or after flutamide therapy, as further evidence of potency. Biochemical analyses of the pre-flutamide ejaculates revealed higher values for markers of prostatic secretion in cases with high level of tumour differentiation. Significant reduction in the secreted amount of prostatic and seminal vesicle parameters was found in all the studied cases during flutamide therapy.

The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio=2.7, P<0.01, 95% confidence interval=1.3–5.8). Quantitative reverse-transcription–polymerase chain reaction demonstrated high estrogen-regulated gene (ERG) expression to be associated with TMPRSS2:ERG fusion (P<0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.Oncogene (2007) 26, 4596–4599; doi:10.1038/sj.onc.1210237; published online 22 January 2007 [ABSTRACT FROM AUTHOR]

Cytochrome P450 (CYP) 7B1 is involved in many metabolic processes including androgen metabolism. Genetic variation in the CYP7B1 gene may play a role in predisposition to prostate cancer. Here, we screened the human CYP7B1 gene for possible polymorphisms. Only one single polymorphism was detected, a C-G change in the promoter -104 base pair from the transcription start site. The allele frequency was investigated in Swedish men and compared to a Korean population, as it is known that the frequency of prostate cancer is low among Orientals. We found that the frequency of the G-allele was 4.04% in Swedes (n=150) but only 0.33% among Koreans (n=153). Computer analysis indicated that the two variants bind with different affinities to a CCAAT-box binding protein. Expression studies with reporter constructs showed significantly higher transcriptional activity of the G variant in Hek293 cells (2.7-fold, P<0.05). In conclusion, we report here for the first time the detection of a single polymorphism in the CYP7B1 gene. This polymorphism is associated with phenotypic differences in an expression system and a widely different allele frequency in two ethnic populations, with great differences in the incidence of prostate cancer.The Pharmacogenomics Journal (2004) 4, 245-250. doi:10.1038/sj.tpj.6500236 Published online 9 March 2004 [ABSTRACT FROM AUTHOR]