The presence of prostate cancer at biopsy is predicted by a number of genetic variants.

Several single nucleotide polymorphisms (SNPs) have been associated with an elevated risk of prostate cancer risk. It is not established if they are useful in predicting the presence of prostate cancer at biopsy or if they can be used to define a low-risk group of men. In this study, 4,548 men underwent a prostate biopsy because of an elevated prostate specific antigen (PSA; ≥4 ng/mL) or an abnormal digital rectal examination (DRE). All men were genotyped for 11 selected SNPs. The effect of each SNP, alone and in combination, on prostate cancer prevalence was studied. Of 4,548 men: 1,834 (40.3%) were found to have cancer. A positive association with prostate cancer was seen for 5 of 11 SNPs studied (rs1800629, rs1859962, rs1447295, rs4430796, rs11228565). The cancer detection rate rose with the number of SNP risk alleles from 29% for men with no variant to 63% for men who carried seven or more risk alleles (OR = 4.2; p = 0.002). The SNP data did not improve the predictive power of clinical factors (age, PSA and DRE) for detecting prostate cancer (AUC: 0.726 vs. 0.735; p = 0.4). We were unable to define a group of men with a sufficiently low prevalence of prostate cancer that a biopsy might have been avoided. In conclusion, our data do not support the routine use of SNP polymorphisms as an adjunct test to be used on the context of prostate biopsy for Polish men with an abnormal screening test.

A common nonsense mutation of the BLM gene and prostate cancer risk and survival.

BACKGROUND: Germline mutations of BRCA2 and NBS1 genes cause inherited recessive chromosomal instability syndromes and predispose to prostate cancer of poor prognosis. Mutations of the BLM gene cause another chromosomal instability clinical syndrome, called Bloom syndrome. Recently, a recurrent truncating mutation of BLM (Q548X) has been associated with a 6-fold increased risk of breast cancer in Russia, Belarus and Ukraine, but its role in prostate cancer etiology and survival has not been investigated yet. METHODS: To establish whether the Q548X allele of the BLM gene is present in Poland, and whether this allele predisposes to poor prognosis prostate cancer, we genotyped 3337 men with prostate cancer and 2604 controls. RESULTS: Q548X was detected in 13 of 3337 (0.4%) men with prostate cancer compared to 15 of 2604 (0.6%) controls (OR=0.7; 95% CI 0.3-1.4). A positive family history of any cancer in a first- or second-degree relative was seen only in 4 of the 13 (30%) mutation positive families, compared to 49% (1485/3001) of the non-carrier families (p=0.3). The mean follow-up was 49months. Survival was similar among carriers of Q548X and non-carriers (HR=1.1; p=0.9). The 5-year survival for men with a BLM mutation was 83%, compared to 72% for mutation-negative cases. CONCLUSIONS: BLM Q548X is a common founder mutation in Poland. We found no evidence that this mutation predisposes one to prostate cancer or affect prostate cancer survival. However, based on the observed 0.6% population frequency of the Q548X allele, we estimate that one in 100,000 children should be affected by Bloom syndrome in Poland.

The G84E mutation in the HOXB13 gene is associated with an increased risk of prostate cancer in Poland.

BACKGROUND: The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer in North America (about 20-fold). The geographical and ethnic extent of this recurrent allele has not yet been determined. METHODS: We assayed for the presence of the G84E mutation in 3,515 prostate cancer patients and 2,604 controls from Poland and estimated the odds ratio for prostate cancer associated with the allele. RESULTS: The G84E mutation was detected in 3 of 2,604 (0.1%) individuals from the general population in Poland and in 20 of 3,515 (0.6%) men with prostate cancer (Odds ratio [OR] = 5.0; 95% CI: 1.5-16.7; P = 0.008). The allele was present in 4 of 416 (1.0%) men with familial prostate cancer (OR = 8.4, 95% CI: 1.9-37.7; P = 0.005). CONCLUSIONS: The G84E mutation predisposes to prostate cancer in Poland, but accounts for only a small proportion of cases. We expect that the G84E founder mutation might be present in other Slavic populations.

Effect of luteinizing hormone-releasing hormone (LHRH) analogue treatment on a cytokine profile in prostate cancer patients.

The aim of the study was to test serum concentrations of the chosen cytokines in patients with prostate cancer (PCa) treated with an luteinizing hormone-releasing hormone (LHRH) analogue. We tested interleukin (IL)-2, IL-10, tumor necrosis factor (TNF)-alpha, interferon (INF)-gamma in blood at three time points; I - before the injection, II - 10 days and III - 20 days after the injection in 14 men with PCa. Patients had one depot injection of the LHRH analogue monthly. The cytokine concentrations in serum samples were determined by ELISA method. Prostate specific antigen (PSA) level was examined before and after six months of the LHRH analogue treatment. After six months of the therapy, we observed normalization of serum PSA value from 16.48 ng/ml to 1.45 ng/ml. LHRH analogue injection resulted in a significant drop of the IL-2 concentration, and the value gradually returned to normal in the next 20 days. IL-10 concentration transiently increased and then was down-regulated. Serum TNF-alpha and INF-gamma concentrations in PCa patients were significantly lower compared to controls and were not affected by the treatment. LHRH analogue treatment in PCa patients modulates concentrations of the chosen cytokines which may result both in antitumor and a transient immunosuppressive effect.

[Assessment of 8-hydroxy-2'-deoxyguanosine concentrations in bladder cancer patients treated with intravesical BCG instillation]. / Analiza stezenia 8-hydroksy-2'-deoxyguanozyny w moczu chorych na powierzchownego raka pecherza moczowego leczonych zawiesina pratka BCG.

UNLABELLED: Increased 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentration has been proposed as reliable marker of the oxidative DNA damage, and prognostication of urological carcinogenesis, particularly in bladder cancer. Widely accepted method of treatment in early stages of bladder cancer is transurethral electro resection (TURN). Intravesical bacillus Calmette-Guerin instillation is considered to be the therapeutic agent for superficial transitional cell carcinoma (TCC) of the bladder and has been established as standard therapy in the patients. The aim of the study was to test the concentration of 8-OHdG in urine in patients with bladder cancer and the effect of TURN and BCG therapy on the 8-OHdG value. MATERIAL AND METHODS: We tested 12 patients (3 female and 9 male) with superficial bladder cancer and 31 healthy controls. Urine for the examination was drawn in 4 time points: before and 2 weeks after TURN treatment, then 6 weeks after 6 intravesical instillations of BCG (Onko BCG--BIO MED Lublin) by Morales and 12 weeks after TURN. 8-OHdG concentration in urine was tested using ELISA commercial kit (OXIS health) and the values of 8-OHdG are expressed as ng/ml of urine. RESULTS: Patients with superficial bladder cancer had 16.89 ng/ml of 8-OHdG in urine before the TURN procedure. The value was significantly (p< 0.005) higher then 12.98 ng/ml noted in healthy controls. 2 weeks after the procedure the 8-OHdG level decreased to 13.36 ng/ml. After 6 weeks of repeated 6 intravesical instillations of the BCG the concentration of 8-OHdG dropped to 10.91 ng/ml (p<0.005) and returned to the value 13.28 ng/ml after the next 4 weeks. CONCLUSIONS: Patients with bladder cancer have significantly increased concentration of 8-OHdG in urine compared to controls. 8 week combine therapy with TURN and BCG resulted in a significant decrease in 8-OHdG concentration in urine The beneficial effect of BCG instillations seems to result from strengthening of the antioxidative DNA protection.

[Evaluation of side effects after intrabladder instillations of preparations in patients with superficial bladder carcinoma]. / Ocena objawów ubocznych preparatów stosowanych w formie instylacji dopecherzowych u chorych z powierzchownym rakiem pecherza moczowego.

Permanent increase in neoplasm incidence including also bladder neoplasms makes physicians to search for new forms and methods of treatment. Application of new preparations entails in many cases appearance of side effects which are difficult to fight off and thus must be monitored constantly. To avoid complications which in case of BCG application are very burdensome and sometimes dangerous for patient it is necessary to intervene in due time. In the years 1990-1998 in Department of urology, Ministry of Internal Affairs and Administration Hospital in Lódz, 241 patients were treated due to superficial bladder carcinoma. In this group in 145 cases after carcinoma electroresection BCG suspension intrabladder infusion were applied. In 42 patients epirubicin, in 16 adriblastin intrabladder instillations were performed; 32 patients did not receive any preparation. A detailed history was taken from the patients before each next infusion, whereas blood was collected for testing before the first infusion and on the seventh day after completion of the therapy. Material for studies was collected before the first intrabladder infusion and on the seventh day after 4-week cycle completion. Side effects of the applied preparations were presented basing on toxicity grades acc. to WHO and divided into subjective and objective ones. The observation period comprised the time from the first infusion to the seventh day after the last infusion. In the group of 145 patients with applied BCG suspension 836 intrabladder instillations were performed. In 17 (12%) cases the treatment was stopped after 4 infusions due to intense dysuric symptoms. In the investigated group of patients strongly marked symptoms like polyuria (in 98% of patients), burning in urethra during miction (in 86%), haematuria and ill-being were observed. Objective symptoms were significantly marked and were not of importance in further management. In group II (epirubicin) and III (adriblastin) both subjective and objective effects were of insignificant percentage and were not of importance in the continuation of the treatment of superficial bladder carcinoma. Accurate subjective examination, careful analysis of the observed unfavourable symptoms, their intensity, close co-operation of the physician with the patient concerning full information on possible complications and side effects and personal procedure with them allow for safe and effective treatment of superficial bladder carcinomas with both BCG suspension and anthracycline antibiotics (in the form of intrabladder infusions).