The Prostate (PROSTATE)

Publications in this journal

• Article: High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and topographical distribution in 1,374 prostatectomy specimens: Existence of HGPIN near prostate cancer.

  Eminaga O, Hinkelammert R, Abbas M, Titze U, Eltze E, Bettendorf O, Semjonow A
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  ABSTRACT: PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is believed to be a precursor of prostate cancer (PCa). This study evaluated whether HGPIN was located close to PCa in whole radical prostatectomy specimens (RPSs). MATERIALS AND METHODS: We evaluated 1,374 prostate specimens from 1999 to 2010 using a cMDX-based map model of the prostate. The distribution of 10,439 PCa foci was analyzed and visualized on a heat map. The color gradient of the heat map was reduced to six colors representing the frequency classification of the relative frequency of PCa using an image posterization effect. We defined 22 regions in the prostate according to the frequency of PCa occurrence. Seven hundred ninety RPSs containing 6,374 PCa foci and 4,502 HGPIN foci were evaluated. The topographical association between PCa and HGPIN in the RPSs was analyzed by estimating the frequencies of PCa and HGPIN in 22 regions. A logistic regression analysis was performed to assess the odds ratios of HGPIN for the presence of PCa in 22 regions. RESULTS: Fifty-eight percent of PCa specimens included HGPIN and had significantly more favorable Gleason scores, lower PSA levels and smaller relative tumor volumes than isolated PCa specimens. HGPIN (68%) and PCa (69%) were predominantly localized to the apical half of the prostate. HGPIN was mainly concentrated in the peripheral zone medial to regions with high PCa frequencies. Upon logistic regression analysis, HGPIN was a significant predictor of PCa co-existence in 11 regions. CONCLUSIONS: HGPIN was located adjacent to PCa in whole RPSs. PCa concomitant with HGPIN had more favorable pathologic features than isolated PCa.
  The Prostate 03/2013;
• Article: Socio-economic status, urbanization grade, and prostate cancer

  J.W.J. van der Gulden, J.J. Kolk, A.L.M. Verbeek
  The Prostate 02/2013; 1994(25):59-65.
• Article: Gene expression in prostate cancer: the importance of the endogenous control.

  Vajda A, Marignol L, Barrett C, Madden S, Hollywood D, Perry A.S
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  ABSTRACT: BACKGROUND: Aberrant gene expression is a hallmark of cancer. Quantitative reverse-transcription PCR (qRT-PCR) is the gold-standard for quantifying gene expression, and commonly employs a house-keeping gene (HKG) as an endogenous control to normalize results; the choice of which is critical for accurate data interpretation. Many factors, including sample type, pathological state, and oxygen levels influence gene expression including putative HKGs. The aim of this study was to determine the suitability of commonly used HKGs for qRT-PCR in prostate cancer. METHODS: Prostate cancer (LNCaP, 22Rv1, PC3, and DU145) and normal (PWR1E and RWPE1) cell lines were cultured in air and hypoxia. The performance of 16 HKGs was assessed using Normfinder and coefficient of variation. In silico promoter analysis was performed to identify putative hypoxia response elements (HREs). The impact of the endogenous control on expression levels of HIF1A and GSTP1 was investigated by qRT-PCR in cell lines and tissue specimens respectively. RESULTS: Hypoxia altered expression of several HKGs: IPO8, B2M, and PGK1. The most stably expressed HKGs were ACTB, PPIA, and UBC. Both UBC and ACTB showed constitutive expression of HIF1A in air and hypoxia, while PGK1 falsely implied a sixfold hypoxia-induced down-regulation. In prostate tumors, UBC and PGK1 both revealed down-regulation of GSTP1 relative to matched benign, whereas ACTB showed variability. CONCLUSIONS: This study demonstrates that no universal endogenous control exists for gene expression studies, even within one disease type. It highlights the importance of validating expression of intended HKGs between different sample types and environmental exposures.
  The Prostate 08/2012;
• Article: Erratum: Prostate-specific genes and their regulation by dihydrotestosterone. Ci M, Mayumi Y, André B, Pascal B, Lin G, Yasukazu T, Fernand L, and Jonny St-Amand. 2008. Prostate 68: 241-254.

  Ci Ma, Mayumi Yoshioka, André Boivin, Pascal Belleau, Lin Gan, Yasukazu Takase, Fernand Labrie, Jonny St-Amand
  The Prostate 10/2008; 68(12):1372.
• Article: Inhibitory effects of nordihydroguaiaretic acid (NDGA) on the IGF-1 receptor and androgen dependent growth of LAPC-4 prostate cancer cells.

  Charles J Ryan, Marianna Zavodovskaya, Jack F Youngren, Michael Campbell, Marc Diamond, Jeremy Jones, Laura Shiry, Geoffrey Allan, Betty A Maddux, Ira D Goldfine
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  ABSTRACT: Nordihydroguaiaretic acid (NDGA) is an inhibitor of the IGF-1 receptor (IGF-1R) in breast and other cancers, and concomitantly inhibits tumor growth both in cultured cells and animals. The current study evaluates the effect of NDGA on the androgen-stimulated growth of human prostate cancer cells. LAPC-4 prostate cancer cells in tissue culture were androgen starved for 3 days, 1 nM dihydrotestosterone (DHT) and other androgens were then added for up to 7 days, and cell proliferation measured. IGF-1R protein expression was measured by Western blot, and IGF-1R mRNA expression by quantitative PCR. IGF-1R receptor kinase activation was measured by ELISA. After 7 days, LAPC-4 growth was doubled by 1 nM DHT. NDGA had a rapid effect to inhibit IGF-1R autophosphorylation induced by IGF-1. DHT increased the expression of IGF-1R protein and mRNA levels. Maximal IGF-1R protein levels were observed 3 days after the addition of androgen. In addition, NDGA, at 10 microM or less, inhibited DHT-induced proliferation in both cells grown in plates and cells grown in soft agar. Androgen receptor (AR) studies by FRET revealed that NDGA had no conformational effects on the AR in response to ligand. NDGA blocks the DHT-induced growth of LAPC-4 prostate cancer cells by several mechanisms including rapid inhibition of the IGF-1R kinase, and a dose-dependent inhibition of androgen stimulation of IGF-1R expression. Clinical studies of this agent will determine its efficacy in the setting of androgen-dependent prostate cancer.
  The Prostate 09/2008; 68(11):1232-40.
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  Available from: umich.edu

  Article: Expression and sub-cellular localization of the CCAAT/enhancer binding protein alpha in relation to postnatal development and malignancy of the prostate.

  Juan Zhang, John Erby Wilkinson, Mesfin Gonit, Rick Keck, Steven Selman, Manohar Ratnam
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  ABSTRACT: C/EBPalpha is a critical mediator of terminal differentiation and a tumor suppressor through its strong antiproliferative actions on cell cycle regulatory proteins. C/EBPalpha also appears to regulate androgen receptor (AR) AR signaling. There, is a paucity of information on the expression and sub-cellular localization of C/EBPalpha in normal mouse and human prostate and in prostate cancer. Immunohistochemistry of tissues including tissue arrays, quantitative polymerase chain reaction and mRNA expression database mining. In the mouse prostate epithelium, C/EBPalpha was present at 1 week postnatal localized in the cytosol, began to show nuclear localization at 8 weeks and continued to show prominent nuclear expression at 10 weeks and beyond; C/EBPalpha mRNA was expressed at all ages. In humans, C/EBPalpha showed prominent nuclear localization from peripubescence up to middle age but was sequestered in the cytosol in older individuals; the mRNA level for C/EBPalpha remained essentially unchanged. Most prostate adenocarcinomas expressed a range of levels of C/EBPalpha mRNA and protein that were relatively high in metastatic tumors in a manner that correlated with AR expression; however, most cells showed C/EBPalpha sequestered in the cytosol. Temporal changes in sub-cellular localization of C/EBPalpha are consistent with a role in prostate differentiation and as a prostate tumor suppressor; the cytoplasmic sequestration of C/EBPalpha, unique to older human prostates, is arguably a permissive condition for the greater frequency of proliferative disorders of the prostate. In malignant prostate C/EBPalpha may be available to regulate AR signaling through transient changes in its sub-cellular localization.
  The Prostate 09/2008; 68(11):1206-14.
• Article: Identification of candidate prostate cancer genes through comparative expression-profiling of seminal vesicle.

  Maxwell Thompson, Jacques Lapointe, Yoon-La Choi, David E Ong, John P Higgins, James D Brooks, Jonathan R Pollack
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  ABSTRACT: Prostate cancer is the most frequently diagnosed cancer among men in the United States. In contrast, cancer of the seminal vesicle is exceedingly rare, despite that the prostate and seminal vesicle share similar histology, secretory function, androgen dependency, blood supply, and (in part) embryonic origin. We hypothesized that gene-expression differences between prostate and seminal vesicle might inform mechanisms underlying the higher incidence of prostate cancer. Whole-genome DNA microarrays were used to profile gene expression of 11 normal prostate and 7 seminal vesicle specimens (including six matched pairs) obtained from radical prostatectomy. Supervised analysis was used to identify genes differentially expressed between normal prostate and seminal vesicle, and this list was then cross-referenced to genes differentially expressed between normal and cancerous prostate. Expression patterns of selected genes were confirmed by immunohistochemistry using a tissue microarray. We identified 32 genes that displayed a highly statistically significant expression pattern with highest levels in seminal vesicle, lower levels in normal prostate, and lowest levels in prostate cancer. Among these genes was the known candidate prostate tumor suppressor GSTP1 (involved in xenobiotic detoxification). The expression pattern of GSTP1 and four other genes, ABCG2 (xenobiotic transport), CRABP2 (retinoic acid signaling), GATA3 (lineage-specific transcription), and SLPI (immune response), was confirmed by immunohistochemistry. Our findings identify candidate prostate cancer genes whose reduced expression in prostate (compared to seminal vesicle) may be permissive to prostate cancer initiation. Such genes and their pathways may inform mechanisms of prostate carcinogenesis, and suggest new opportunities for prostate cancer prevention.
  The Prostate 09/2008; 68(11):1248-56.
• Article: A methyl-deficient diet modifies histone methylation and alters Igf2 and H19 repression in the prostate.

  Joseph R Dobosy, Vivian X Fu, Joshua A Desotelle, Rajini Srinivasan, Michelle L Kenowski, Nima Almassi, Richard Weindruch, John Svaren, David F Jarrard
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  ABSTRACT: Folate and methyl-group deficiency has been linked to prostate cancer susceptibility, yet the mechanisms underlying these observations are incompletely understood. The region of the genome containing the imprinted genes insulin-like growth factor 2 (Igf2) and H19, both of which display oncogenic functions, may be particularly sensitive to environmental influences. To determine whether a methyl-deficient diet impacts epigenetic controls at the Igf2-H19 locus, we placed C57BL/6 mice containing a polymorphism at the imprinted Igf2-H19 locus on a choline and methionine deficient (CMD) diet. We interrogated this locus for expression and epigenetic changes in prostate tissues. A significant increase in both Igf2 and H19 expression was found in CMD prostate tissues compared to controls. These expression changes were reversible with shorter exposure to the CMD diet. Chromatin immunoprecipitation (ChIP) revealed significant decreases in repressive histone modifications (dimethyl-H3K9) within the H19 promoter, as well as Igf2 P2 and P3 promoters. DNA methylation within these promoters was not altered. No significant change in Igf2 or H19 imprinting was observed. These findings highlight the plasticity of the epigenome in an epithelial organ vulnerable to neoplastic change. They further suggest that chromatin modifications are more susceptible to methyl-deficient diets than DNA methylation at this locus.
  The Prostate 09/2008; 68(11):1187-95.
• Article: Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results.

  Martijn P M Q van Gils, Daphne Hessels, Christina A Hulsbergen-van de Kaa, J Alfred Witjes, Cornelius F J Jansen, Peter F A Mulders, Harry G Rittenhouse, Jack A Schalken
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  ABSTRACT: Due to the drawbacks of serum prostate-specific antigen, there is an ongoing search for new diagnostic and prognostic prostate cancer (PCa) markers. PCA3 has proven to be of value in the diagnosis of PCa. However, so far few attempts have been made to investigate the prognostic value of PCA3. Our objective was to further investigate the prognostic value of PCA3. In this study we correlated the PCA3 score in urinary sediments after digital rectal examination in 62 men with the classical prognostic parameters assessed in radical prostatectomy specimens (i.e. Gleason score, pathological tumor stage and total tumor volume) and moreover, with the expression of three immunohistochemical markers for PCa biological aggressiveness (i.e. E-cadherin, alpha-catenin and EZH2). The results from this study serve as a reflection on and a valuable adjunct to recently published results. We did not find a significant correlation of the PCA3 score with the classical prognostic parameters assessed in radical prostatectomy specimens or the expression of the immunohistochemical markers for PCa biological aggressiveness. However, we did observe a trend for a higher PCA3 score in significant PCa versus insignificant PCa, aberrant E-cadherin staining versus normal E-cadherin staining and increased EZH2 staining versus normal EZH2 staining. In this study we could not prove the prognostic value of PCA3. Further research with large numbers of men and adequate follow-up is needed to provide a definitive answer to the question if PCA3 is not only a diagnostic but also a prognostic PCa marker.
  The Prostate 09/2008; 68(11):1215-22.
• Article: Are prostate biopsies mandatory in patients with prostate-specific antigen increase during intravesical immuno- or chemotherapy for superficial bladder cancer?

  Paolo Beltrami, Lorenzo Ruggera, Lucia Cazzoletti, Dionisio Schiavone, Filiberto Zattoni
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  ABSTRACT: Aim of this study was to evaluate if there was a significant association between intravesical immuno- or chemotherapy and the increase of PSA serum level. It could be important to avoid useless prostate biopsies. PSA values were determined in 106 male patients who had undergone intravesical immuno- (77 cases) or chemotherapy (29 cases) from 2001 to 2005. Blood samples were obtained before and after the induction course of instillation therapy and at 3, 6, and 12 months during the maintenance course. 41.6% of patients at the end of the BCG induction course and 45.5% at 3 months from the beginning of the immunotherapy showed a clinically and statistically significant increase of PSA that returned to the baseline levels within 12 months. Prostate biopsies, performed in 10 patients during BCG therapy, showed inflammatory pictures in 9 cases and a prostate cancer in 1 patient with persistently elevated PSA at 12 months. In 1 case a prostate cancer was histologically found following radical cystectomy for disease progression. A statistically but not clinically significant difference of PSA level was registered in patients treated with chemotherapy. Our results confirm that a statistically and clinically significant PSA increase is registered during immunotherapy but not during chemotherapy. PSA elevation in patients treated with intravesical BCG is self-limited and prostate biopsies are not mandatory in these patients and could be delayed at 12 months, while monitoring PSA. On the other side, prostate biopsies are mandatory in patients with PSA abnormal elevation during chemotherapy.
  The Prostate 09/2008; 68(11):1241-7.
• Article: Hormonal regulation of beta2-adrenergic receptor level in prostate cancer.

  Håkon Ramberg, Turid Eide, Kurt Allen Krobert, Finn Olav Levy, Nishtman Dizeyi, Anders S Bjartell, Per-Anders Abrahamsson, Kristin Austlid Taskén
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  ABSTRACT: Androgen deprivation is the only effective systemic therapy available for patients with prostatic carcinoma, but is associated with a gradual transition to a hormone-refractory prostate cancer (HRCAP) in which ligand-independent activation of the androgen receptor has been implicated. The beta(2)-adrenergic receptor (beta(2)-AR) is a well-known activator of the androgen receptor. Prostatic cell lines were analyzed using cDNA micro-array, real time RT-PCR, radioligand binding assay, cAMP measurements, transfection and thymidine incorporation assay. Clinical specimens were studied by immunohistochemistry and Affymetrix microarrays. Here, we show that beta(2)-AR was transiently down-regulated both at mRNA- and protein levels when hormone-sensitive prostate cancer cells, LNCaP, were cultured in steroid stripped medium (charcoal-stripped fetal calf serum) or when the cells were treated with the anti-androgen, bicalutamide (Casodex). The number of beta-adrenergic receptors was modestly up-regulated in androgen independent cell lines (LNCaP-C4, LNCaP-C4-2 and DU145) compared to LNCaP. Triiodothyronine (T3) increased the level of beta(2)-AR and the effect of T3 was inhibited by bicalutamide. Immunohistochemical staining of human prostate specimens showed high expression of beta(2)-AR in glandular, epithelial cells and increased expression in malignant cells compared to benign hyperplasia and normal tissue. Interestingly, beta(2)-AR mRNA was strongly down-regulated by androgen ablation therapy of prostate cancer patients. The level of beta(2)-AR was increased by T3 in prostatic adenocarcinoma cells and reduced in prostate cancer patients who had received androgen ablation therapy for 3 months.
  The Prostate 08/2008; 68(10):1133-42.
• Article: Zoledronic acid decreased osteolysis but not bone metastasis in a nude mouse model of canine prostate cancer with mixed bone lesions.

  Nanda K Thudi, Chelsea K Martin, Murali V P Nadella, Soledad A Fernandez, Jillian L Werbeck, Joseph J Pinzone, Thomas J Rosol
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  ABSTRACT: Bone metastasis is the most common cause of morbidity and mortality in patients with advanced prostate cancer and is manifested primarily as mixed osteoblastic and osteolytic lesions. However, the mechanisms responsible for bone metastases in prostate cancer are not clearly understood, in part due to the lack of relevant in vivo models that mimic the clinical presentation of the disease in humans. We previously established a nude mouse model with mixed bone metastases using intracardiac injection of canine prostate cancer cells (Ace-1). In this study, we hypothesized that tumor-induced osteolysis promoted the incidence of bone metastases and osteoblastic activity. We studied the effect of inhibition of osteolysis with zoledronic acid (ZA) on the prevention and progression of Ace-1 bone metastases in nude mice using prophylactic and delayed treatment protocols. Bioluminescent imaging, radiography, and histopathological evaluation were performed to monitor the effect of ZA on the incidence, progression and nature of bone metastases. Unexpectedly, there was no significant difference in tumor burden and the incidence of metastasis between control and treatment groups as detected by bioluminescent imaging and bone histomorphometry. However, radiographic and histopathological analysis showed a significant treatment-related decrease in osteolysis, but no effect on tumor-induced trabecular bone thickness in both treatment groups compared to controls. Our results demonstrated that the incidence of prostate cancer bone metastases in vivo was not reduced by zoledronic acid even though zoledronic acid inhibited bone resorption and bone loss associated with the mixed osteoblastic/osteolytic bone metastases in the Ace-1 model.
  The Prostate 08/2008; 68(10):1116-25.
• Article: Alterations in beta-catenin expression and localization in prostate cancer.

  Hayley C Whitaker, Joanne Girling, Anne Y Warren, Hing Leung, Ian G Mills, David E Neal
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  ABSTRACT: Wnt signaling is thought to be important in prostate cancer, in part because proteins such as beta-catenin can also affect androgen receptor signaling. beta-Catenin forms a cell adhesion complex with E-cadherin raising the possibility that loss of expression or a change in beta-catenin distribution in the cell could also alter downstream signaling, decreased inter-cellular adhesion and the promotion of metastasis. A number of studies have reported the altered expression and/or localization of beta-catenin as a biomarker in prostate cancer. Tissue microarrays comprised of BPH and low, moderate and high-grade prostate cancer (n=77) were assessed for beta-catenin expression and distribution using immunohistochemistry. Staining was also performed on a tissue microarray containing tissue from patients before and after hormone manipulation. The effects of fixation and different antibodies was assessed on fixed LNCaP cell pellets and small prostate tissue microarrays. We have observed increased beta-catenin expression in only high Gleason score (>7) prostate cancer. A nuclear re-distribution of beta-catenin has previously been reported. We noted nuclear beta-catenin in benign prostatic hyperplasia and a gradual loss in nuclear distribution with increasing Gleason grade. We found no evidence for an alteration in beta-catenin expression or re-distribution with hormone ablation. Altered fixation, antibodies and antibody concentration did affect the intensity and specificity of staining. A loss of nuclear beta-catenin is the most consistent feature in prostate cancer rather than absolute levels of expression. We also suggest that variation in immunohistochemical protocols may explain variations in the reported literature.
  The Prostate 08/2008; 68(11):1196-205.
• Article: Prediction of lymphatic invasion by peritumoral lymphatic vessel density in prostate biopsy cores.

  Kenji Kuroda, Akio Horiguchi, Takako Asano, Tomohiko Asano, Masamichi Hayakawa
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  ABSTRACT: Lymphatic invasion in radical prostatectomy specimens has been suggested to be an unfavorable prognostic factor in clinically localized prostate cancer. Lymphangiogenesis detected by antibodies specific for lymphatic endothelial cells has been associated with lymphatic invasion and lymph node metastasis in prostate cancer. This study was designed to examine whether lymphangiogenesis in prostate biopsy could predict lymphatic spread in radical prostatectomy specimens. Paraffin-embedded positive biopsy cores obtained from 99 patients who underwent radical prostatectomy at our institution were immunostained with D2-40 monoclonal antibody, which specifically recognizes lymphatic endothelium. The association between lymphatic parameters in prostate biopsy and pathological parameters in radical prostatectomy specimens was analyzed. Peritumoral and intratumoral lymphatic (ITL) vessels were observed in 90 (90.9%) and 23 cases (23.2%). Average and maximal peritumoral lymphatic vessel density (PTLD) and the presence of ITL in positive biopsy cores were significantly associated with positive biopsy core rates (P = 0.0015 for average PTLD, P < 0.0001 for maximal PTLD, and P = 0.0038 for ITL) and lymphatic vessel invasion (P < 0.0001 for average PTLD, P < 0.0001 for maximal PTLD, and P = 0.0322 for ITL). Among preoperative parameters, the biopsy Gleason score (P = 0.0092, HR = 6.108) and average PTLD (P = 0.0034, HR = 1.860) were significant predictors of lymphatic invasion in radical prostatectomy specimens in multivariate analysis. PTLD in prostate biopsy specimens assessed by immunohistochemistry using D2-40 antibody could be a useful parameter for predicting lymphatic spread of clinically localized prostate cancer.
  The Prostate 08/2008; 68(10):1057-63.
• Article: Vasculature-targeted tumor necrosis factor-alpha increases the therapeutic index of doxorubicin against prostate cancer.

  Maria T S Bertilaccio, Matteo Grioni, Brent W Sutherland, Elena Degl'Innocenti, Massimo Freschi, Elena Jachetti, Norman M Greenberg, Angelo Corti, Matteo Bellone
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  ABSTRACT: Poor penetration and uneven distribution of doxorubicin in tumors limits the efficacy of this drug in patients with prostate cancer (PC). Aim of the study was to investigate whether pre-treatment with NGR-TNF, a tumor necrosis factor-alpha derivative able to target tumor vessels and alter vessel permeability, increases the penetration and the efficacy of doxorubicin in pre-clinical models of PC. Wild type C57BL/6 mice bearing androgen-independent TRAMP-C1 PC and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, which spontaneously develop PC and metastasis, were treated with repeated cycles of doxorubicin, administered either alone or following NGR-TNF. Tumor growth and drug uptake by cancer cells was evaluated. Doxorubicin as a single agent blocked the growth of TRAMP-C1 cells in vitro but not in vivo. Pre-treatment of mice bearing subcutaneous TRAMP-C1 tumors with NGR-TNF favored doxorubicin penetration into the tumor mass, and in both TRAMP-C1 and TRAMP models significantly delayed tumor growth without increasing drug-related toxicity. Pre-treatment with NGR-TNF significantly expanded the therapeutic index of doxorubicin in mouse models of hormone-dependent and -independent PC.
  The Prostate 08/2008; 68(10):1105-15.
• Article: Association between polymorphisms in cell cycle genes and advanced prostate carcinoma.

  Adam S Kibel, Carol H Jin, Aleksandra Klim, Jason Luly, Kimberly A Roehl, William S Wu, Brian K Suarez
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  ABSTRACT: Single nucleotide polymorphisms (SNPs) have been associated with a variety of malignancies including prostate carcinoma (PCa). Since a high percentage of PCa patients have low risk disease, of particular interest is not whether SNPs are associated with localized PCa, but whether they are associated with aggressive, potentially lethal disease. Herein, we explored the role of SNPs in cell cycle genes to determine if they were associated with advanced PCa. Nine previously implicated SNPs in six cell cycle genes were evaluated in a European-American cohort of 186 patients with advanced PCa and 222 cancer-free controls. All patients received hormone ablation and had either a PSA>50 ng/ml or documented metastatic disease. Controls were all 75 years of age or older, had a negative DRE and had a PSA<4.0 ng/ml. All genotypes were determined using Pyrosequencing assays. One of nine (CDKN1A c10791t) was statistically different (P<0.05) and an additional two of nine (CCND1 a870g and MDM2 tSNP309g) approached significance (P<0.1). Analysis of genotypes revealed that presence of at least one copy of the t allele of MDM2 tSNP309g was associated with an increased risk of advanced PCa (OR 2.26: 95% CI=1.15-4.46) which was particularly strong in androgen-independent disease (OR 2.28: 95% CI=1.01-5.12) and younger age of diagnosis (OR 2.61: 95% CI=1.05-6.46). These results suggest that in a European-American population, SNPs within cell cycle genes are promising markers for aggressive PCa. Larger studies will be needed to confirm these findings.
  The Prostate 08/2008; 68(11):1179-86.