423 GENETIC POLYMORPHISMS FOR PREDICTING PROSTATE CANCER MORTALITY

420

Serum antibodies against genitourinary infectious agents in prostate cancer and benign prostate hyperplasia patients

Hrbáček J.1, Urban M.1, Hamšíková E.2, Tachezy R.2, Eis V.3, Brabec M.4, Heráček J.1 1 Charles University, 3rd Faculty of Medicine, Dept. of Urology, Prague, Czech Republic, 2Institute of Haematology and Blood Transfusion, Experimental Virology Dept., Prague, Czech Republic, 3Charles University, 3rd Faculty of Medicine, Dept. of Pathology, Prague, Czech Republic, 4Institute of Computer Science, Academy of Sciences of The Czech Republic, Dept. of Nonlinear Modelling, Prague, Czech Republic Introduction & Objectives: Infection plays a role in the pathogenesis of many human malignancies. Whether prostate cancer (PCa) belongs to these has been investigated in several studies so far with inconsistent methodology and disappointing results. The aim of the study was to compare seroprevalence and serum antibody levels in PCa and benign prostate hyperplasia (BPH) patients and to correlate histopathological findings in tissue specimens with tumor grade and stage. Materials & Methods: A total of 434 males who underwent open prostate surgery were included in the study: 329 PCa patients (mean age 64 years, mean prostate specific antigen (PSA) level 9.0 ng/mL; 47.7% with localized disease; 52.3% with locally advanced PCa; 51.4% with Gleason score (GS) 2-6, 10.9% with GS 8-10) and 105 controls with BPH (mean age 72 years, mean PSA 7.5 ng/mL). The subjects’ serum samples were analysed by means of enzyme-linked immunosorbent assay, complement fixation test and indirect immunofluorescence for presence of antibodies against human papillomavirus (HPV) 6, 11, 16, 18, 31 and 33, herpes simplex virus 1 and 2, human cytomegalovirus (CMV), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Neisseria gonorrhoeae and Treponema pallidum. Antibody seroprevalence and mean serum antibody levels were compared between cases and controls. Tumour grade and stage were correlated with serological findings. Results: PCa patients were more likely to harbour antibodies against Ureaplasma urealyticum (OR 2.06; 95% CI 1.08-4.28). Men with BPH were more likely to be seropositive for HPV 18 (OR 0.23; 95% CI 0.09-0.61) and Chlamydia trachomatis (OR 0.45; 95% CI 0.21-0.99) and had higher mean serum CMV antibody levels than PCa patients (p=0.0004). For other pathogens, the differences in seroprevalence and mean serum antibody levels were not statistically significant. Among PCa patients, antibodies against HPV 6 were associated with higher Gleason score (p=0.0305). No association was demonstrated between seropositivity to any of infectious agents studied and PSA level, seropositivity and GS, seropositivity and localized versus locally advanced disease stage. Conclusions: Presence and/or higher levels of serum antibodies against genitourinary pathogens studied except for Ureaplasma were not consistently associated with PCa. Antibody seropositivity against analyzed pathogens does not seem to be a risk factor for PCa pathogenesis. The study was funded by the Internal Grant Agency of the Ministry of Health, grant no. NS9984.

421

Psychosocial distress in prostate cancer patients: Does family history make a difference?

Herkommer K.1, Dinkel A.2, Kornmayer M.1, Herschbach P.2, Gschwend J.E.1 1 Klinikum Rechts der Isar der TU München, Dept. of Urology, Munich, Germany, 2 Klinikum Rechts der Isar der TU München, Dept. of Psychosomatic Medicine and Psychotherapy, Munich, Germany Introduction & Objectives: A positive family history is one of the strongest risk factors to develop prostate cancer. Thus, it seems reasonable that patients with a familial history of prostate cancer might worry about passing their disease to their kin. However, to date no study investigated the effect of family history of prostate cancer on psychosocial distress in affected men. Materials & Methods: Nationwide 3.527 patients who were treated with radical prostatectomy between 2000 and 2005 were included in this study and completed a mail survey in 2009. Mean current age was 71.2 years (SD = 6.5; range 45 – 92). The patients were divided into 3 subgroups according to their family history: 68.0% (n=2.399) sporadic, 25.9% (n=915) familial (at least one first-degree relative with PC), and 6.1% (n=213) hereditary (according to the Johns Hopkins criteria). Cancer-specific distress was assessed with the Questionnaire on Distress in Cancer Patients – Short Form (QSC-R10), depression and anxiety were assessed with a short form of the Patient Health Questionnaire (PHQ-4). We investigated the influence of family history, age at diagnosis (< 65 vs. ≥ 65 years), and biochemical recurrence (Follow-up: PSA >0.2ng/ml) on psychosocial distress. Results: The prevalence of cancer-specific distress was 16.4%. Regarding specific concerns, feeling physically imperfect (12.3%) and fear of disease progression (6.2%) were most prevalent. Depression was prevalent in 6.0%, and anxiety in 6.3%. Age at diagnosis was associated with each psychosocial distress measure (p < .001), i.e. younger patients showed higher distress. Furthermore, biochemical recurrence was associated with higher cancer-specific distress (p<.001) and with higher depression as well as anxiety scores (p<.01). Family history was not directly associated with the distress measures, and did not interact with age at diagnosis or biochemical recurrence. Conclusions: Patients without biochemical recurrence of prostate cancer showed

Eur Urol Suppl 2011;10(2):146

low rates of psychosocial distress. Those who received diagnosis at age before 65 years and those who had a biochemical recurrence in the meantime reported higher cancer-specific distress, depression and anxiety. Surprisingly, family history of prostate cancer showed neither a direct nor a moderating effect on psychosocial distress. Our data do not allow to decide whether this is due to successful coping, no known prostate cancer genes, or some other variables.

422

WITHDRAWN

423

Genetic polymorphisms for predicting prostate cancer mortality

Suzuki M.1, Liu M.1, Fujimura T.1, Fukuhara H.1, Enomoto Y.1, Nishimatsu H.1, Ishikawa A.1, Kume H.1, Homma Y.1, Kitamura T.2 1 The University of Tokyo, Dept. of Urology, Tokyo, Japan, 2Asoka Hospital, Dept. of Urology, Tokyo, Japan Introduction & Objectives: Replication studies had revealed that genetic variants onchromosome 8q24 and 17q were associated with prostate cancer susceptibility in several Asian population. In the present study, we investigated the performance of single-nucleotide polymorphisms located on 8q24 and 17q for prostate cancer susceptibility and mortality with a Japanese men. Materials & Methods: Five-hundred eighteen Japanese patients with sporadic prostate cancer and 323 controls were involved in this study. We performed a replication study to search for genetic variants located on 8q24 and 17q conferring risk of prostate cancer. We selected five polymorphisms, such as rs6983561, rs6983267, rs1447295 located on 8q24 and rs4430796 and rs1859962 located on 17q. Genotyping method we used was a TaqMan assay. We estimated the causespecific survival and overall survival by using the Cox proportional hazards model. Results: Allele wisely, re6983561 (8q24) and rs4430796 (17q12) were significant risk factor for prostate cancer susceptibility in a Japanese population. The odds ratios of these polymorphisms were 1.550 (95% CI, 1.198 to 2.014) in rs6983561 and 1.350 (95% CI, 1.081 to 1.685) in rs4430796, respectively. Concerning with prognosis, patients with AC+CC genotypes of rs6983561 survived longer than patients with AA genotype. The hazard ratios for prostate cancer-specific survival and overall survival were 2.438 (95% CI, 1.262 to 5.046) and 1.957 (95% CI, 1.142 to 3.485), respectively. The impact of rs6983561 for survival was enhanced in the restricted analysis in patients having metastasis; the hazard ratios for prostate cancer-specific survival and overall survival were 3.353 (95% CI 1.689 to 7.446) and 3.361 (95% CI, 1.741 to 7.136). Conclusions: Rs6983561 polymorphism is significantly associated with both prostate cancer susceptibility and mortality.

424

Prostate cancer screening: Can it be improved with total testosterone levels?

Botelho F.1, Pina F.1, Figueiredo L.1, Ramos J.2, Guimarães T.3, Cruz F.1 1 Hospital S. João, Dept. of Urology, Porto, Portugal, 2Hospital S. João, Dept. of Immunology, Porto, Portugal, 3Hospital S. João, Dept. of Clinical Pathology, Porto, Portugal Introduction & Objectives: Prostate cancer (PC) is an endocrine-responsive tumor and several pathways may explain the association between serum total Testosterone (tT) and PC. Previous studies on this topic are conflicting with some authors defending that either tT or the ratio tT/total PSA (tPSA) can be lower in patients with PC, particularly in patients with lower tPSA. However none of these investigations evaluate patients with prostatitis or high grade prostate intraepithelial neoplasia (HGPIN) as individual groups, none had samples bigger than 600 patients, and some suffer from limited challenged bias. Our objective was to evaluate tT as a diagnostic tool for PC, using a large sample of patients with increased risk of PC and presenting different prostatic pathologies. Materials & Methods: We consecutively enrolled 1577 candidates referred to ultrasound guided trans-rectal prostate biopsy in S. João Hospital (median tPSA: 7.0ng/mL), in whom tT, tPSA, and free PSA (fPSA) were measured in fast blood samples collected before biopsy. Groups were compared using Kruskal-Wallis test, and Spearman correlation coefficients were computed to quantify the association between continuous variables. Diagnostic capability of the different biomarkers was evaluated with receiver operating characteristic (ROC) analysis. Analyses were repeated using only patients with tPSA < 4ng/mL. Results: Prostatic biopsies revealed PC in 620 cases (39.3%), HGPIN in 51 cases (3.2%), pathological prostatitis in 624 cases (39.6%), BPH or no alteration (BPH/N) in 282 cases (17.9%). No difference was observed when comparing tT levels between prostatic biopsy pathologies (median: 4.26 vs. 4.44 vs. 4.31 vs. 4.16 pg/mL, respectively; p=0.58). The tT level were the same in prostatic cancer and benign pathology (median: 4.25 vs. 4.25 pg/mL, respectively; p=0.97). No significant correlations were observed between tT and age (r=-0.002; p=0.94), tPSA (r=-0.034; p=0.20), or f/t PSA ratio (r=0.029; p=0.282). Considering ROC analysis tT/tPSA ratio is a better diagnostic test than tT alone (AUC of 0.62 (95%CI: 0.59-0.65) vs. 0.51 (95%CI: 0.48-0.53)), but worse than f/t PSA ratio (AUC: 0.70 (95%CI: 0.67-0.73)). In PC patients the tT levels were not significantly different