Real-World Safety and Efficacy Outcomes with Abiraterone Acetate Plus Prednisone or Prednisolone as the First- or Second-Line Treatment for Metastatic Castration-Resistant Prostate Cancer: Data from the Prostate Cancer Registry.

Background: Despite standard-of-care androgen-deprivation therapy and an increasing number of treatment options, the mortality rate for prostate cancer remains high. Progress to metastatic castration-resistant prostate cancer (mCRPC) necessitates additional treatments. Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

Real-World Outcomes in First-Line Treatment of Metastatic Castration-Resistant Prostate Cancer: The Prostate Cancer Registry.

Background: Metastatic prostate cancer has a 30% 5-year survival rate despite recent therapeutic advances. There is a need to improve the clinical understanding and treatment of this disease, particularly in the real-world setting and among patients who are under-represented in clinical trials.

Objective: We aimed to evaluate the characteristics and clinical outcomes of patients who received their first treatment for metastatic castration-resistant prostate cancer (mCRPC) in routine clinical practice, independent of treatment used, including subgroups with baseline cardiac disease, diabetes mellitus, or visceral metastases.

Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics using novel sumLINK and sumLOD analyses.

Background: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity.

Methods: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD.

Genome-wide linkage analysis of TMPRSS2-ERG fusion in familial prostate cancer.

Fusion of the 5'-untranslated region of androgen-regulated TMPRSS2 promoter with ETS transcription factor family members is found frequently in prostate cancers, and recent work suggests that the most common TMPRSS2-ERG fusion is associated with an aggressive clinical phenotype compared with fusion-negative prostate cancer. Thus far, analysis of the fusion has been limited to sporadic cases of prostate cancer. In the current study, we explore for an enrichment of TMPRSS2-ERG fusion in familial prostate cancer.

The correlation between male age, sperm quality and sperm DNA fragmentation in 320 men attending a fertility center.

Purpose: To investigate the effects of male aging on sperm quality and sperm DNA fragmentation.

Methods: The ejaculates of 320 unselected men attending a fertility clinic and, as a control, 84 normozoospermic men without any history of ART were analyzed according to WHO guidelines. Sperm DNA fragmentation was measured by flow cytometry after staining with propidiumiodide.

Expression changes of CAV1 and EZH2, located on 7q31 approximately q36, are rarely related to genomic alterations in primary prostate carcinoma.

The chromosomal region 7q was repeatedly found to be rearranged in prostate carcinoma. It harbors several well described candidate tumor suppressor and oncogenes. We addressed two genes with opposite roles in cancer; CAV1, a putative tumor suppressor gene at 7q31, and EZH2 at 7q36, which is believed to promote tumor progression.

Compelling evidence for a prostate cancer gene at 22q12.3 by the International Consortium for Prostate Cancer Genetics.

Previously, an analysis of 14 extended, high-risk Utah pedigrees localized in the chromosome 22q linkage region to 3.2 Mb at 22q12.3-13.

[Association of a positive family history with histopathology and clinical course in early-onset prostate cancer].

Background: In a large number of studies a positive family history is documented as one of the main risk factors for the development of prostate cancer. In a US population an association between early-onset prostate cancer among familial patients and a more differentiated tumour was shown. The aim of this study was to compare clinical parameters between sporadic and familial or hereditary patients with an age at diagnosis < or =55 years.

Pooled genome linkage scan of aggressive prostate cancer: results from the International Consortium for Prostate Cancer Genetics.

While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms could provide important prognostic information relevant to more effective clinical management of this heterogeneous cancer. Hence, through genetic linkage analyses, we examined the hypothesis that the tendency to develop aggressive prostate cancer may have an important genetic component.

[Prospective evaluation of prostate cancer screening in men with a family history of the disease].

Background: Family history is one of the strongest risk factors for prostate cancer. In this prospective study we evaluated the results of prostate cancer screening performed in healthy brothers of prostate cancer patients. The detection rate of prostate cancer and the positive predictive value of the examinations were determined.

Role of the Nijmegen breakage syndrome 1 gene in familial and sporadic prostate cancer.

The Nijmegen breakage syndrome 1 (NBS1) gene, which participates in DNA double strand break repair, has been postulated to be a susceptibility factor for a number of cancers, including prostate cancer. Numerous mutations have been identified in NBS1, including the founder mutation 657del5. In this study, a number of analyses were done to determine whether mutations in NBS1 are associated with an increased risk for prostate cancer.

[Klippel-Trénaunay syndrome. A rare cause of recurrent macrohematuria: case report].

A 37-year-old man with Klippel-Trénaunay syndrome presented with an episode of painless severe gross hematuria. Magnetic resonance imaging (MRI) revealed vessels of significant diameter in the bladder wall. Diagnostic imaging is mandatory in order to be aware of the extent of the lesion as the bleeding identified intraoperatively may only be the "tip of the iceberg.

Germline mutations of the MSR1 gene in prostate cancer families from Germany.

The MSR1 gene at 8p22 has been suggested as a candidate gene for hereditary prostate cancer because germline variants have been found to be associated with the disease. Aside from a single nonsense mutation (R293X) that was found repeatedly at low frequencies in several samples, little evidence has been gained by follow-up studies to confirm the gene's relevance for prostate cancer. Prompted by reasonable support for a linkage to 8p22, we sought to determine the mutation spectrum of MSR1 in our family sample.

Radiosensitivity detected by the micronucleus test is not generally increased in sporadic prostate cancer patients.

The micronucleus test (MNT) has shown increased micronuclei (MN) frequencies in BRCA associated and sporadic breast cancer patients, Ataxia telangiectasia and Nijmegen Breakage Syndrome patients, demonstrating a common cellular phenotype of increased radiosensitivity. Some genes, causative of these diseases, have also recently been associated with prostate cancer. In order to investigate if prostate cancer exhibits the cellular phenotype of increased radiosensitivity, we performed MNT analysis on 22 sporadic prostate cancer patients and 43 male controls.

Mutation screen and association study of EZH2 as a susceptibility gene for aggressive prostate cancer.

Background: Several linkage studies have provided evidence for a prostate cancer aggressiveness gene on chromosome 7q. This report details the results of the first mutation screen and association study of EZH2 (located at 7q35) as a potential candidate gene for the development of aggressive prostate cancer.

Methods: In 10 families with linkage of chromosome 7q31-33 to aggressive prostate cancer, we sequenced the promoter region and all 20 exons of EZH2.

A combined genomewide linkage scan of 1,233 families for prostate cancer-susceptibility genes conducted by the international consortium for prostate cancer genetics.

Evidence of the existence of major prostate cancer (PC)-susceptibility genes has been provided by multiple segregation analyses. Although genomewide screens have been performed in over a dozen independent studies, few chromosomal regions have been consistently identified as regions of interest. One of the major difficulties is genetic heterogeneity, possibly due to multiple, incompletely penetrant PC-susceptibility genes.

Association of a CAV-1 haplotype to familial aggressive prostate cancer.

Background: Multiple lines of evidence have implicated the CAV-1 gene in prostate cancer progression. CAV-1 is located within the prostate cancer aggressiveness locus at 7q31-33, and was identified as being overexpressed in prostate tumors. Mutation screening was performed as well as a case-control study to examine if polymorphisms in CAV-1 are associated with prostate cancer aggressiveness in a German population.

Role of a CYP17 promoter polymorphism for familial prostate cancer risk in Germany.

Background: A thymidine to cytosine transition (designated A2 variant) in the promoter region of CYP17 has previously been associated with a familial history of prostate cancer in North American families. The purpose of the present study was to determine whether this correlation could be replicated in a European population.

Materials And Methods: Case-control comparisons were performed by modelling a dominant (A1/A2 + A2/A2 vs.

[Is the prostate cancer screening behaviour of men with familial predisposition predictable?].

Little is known about the motives of German men to attend or refuse preventive checkups for prostate cancer. The aims of this study were to investigate if in men with familial predisposition screening behaviours are influenced by epidemiological or clinical parameters of prostate cancer of their affected relatives. 476 probands with one and 312 probands with at least two affected relatives were advised in writing to have a PSA-test and DRE done at their local urologists.

Mutation screening and association study of RNASEL as a prostate cancer susceptibility gene.

To date, germline mutations have been found in three candidate genes for hereditary prostate cancer: ELAC2 at 17p11, RNASEL at 1q25 and MSR1 at 8p22. RNASEL, encoding the 2',5'-oligoadenylate-dependant RNase L, seems to have rare mutations in different ethnicities, such as M1I in Afro-Americans, E265X in men of European descent and 471delAAAG in Ashkenazi Jews. In order to evaluate the relevance of RNASEL in the German population, we sequenced its open reading frame to determine the spectrum and frequency of germline mutations.

A genomewide linkage analysis for prostate cancer susceptibility genes in families from Germany.

Prostate cancer is a complex disease with a substantial genetic contribution involved in the disease risk. Several genomewide linkage studies conducted so far have demonstrated a strong heterogeneity of susceptibility. In order to assess candidate regions that are particularly relevant for the German population, we performed a genomewide linkage search on 139 prostate cancer families.

[Familial versus sporadic prostate cancer in the German population. Clinical and pathological characteristics in patients after radical prostatectomy].

Family history is one of the strongest epidemiological risk factors for the development of prostate cancer. The impact on the clinical presentation and prognosis, however, is controversial. In the present study, we analyzed 464 familial and 492 sporadic prostate cancer patients following radical prostatectomy.

Association between the clinical presentation and epidemiological features of familial prostate cancer in patients selected for radical prostatectomy.

Objective: We evaluated if epidemiological features of familial prostate cancer are associated with certain clinical or histopathological characteristics of the disease.

Methods: 463 German patients with familial prostate cancer who underwent radical prostatectomy were stratified according to several epidemiological criteria: (1). the apparent mode of disease transmission, (2).

Linkage of aggressive prostate cancer to chromosome 7q31-33 in German prostate cancer families.

It has been suggested that chromosome 7q32 contains genes that influence the progression of prostate cancer from latent to invasive disease. In an attempt to confirm this linkage to prostate cancer aggressiveness, 100 German prostate cancer families were genotyped using a panel of eight polymorphic markers on chromosome 7q. We used a multipoint allele sharing method based upon a likelihood ratio test implemented in GENEHUNTERPLUS v1.

[Preventing prostate carcinoma in men with familial disposition].

A family history is one of the strongest risk factors for prostate cancer (PC). We evaluated the detection rate of PC in relatives of 119 German PC families that took part in ongoing linkage analyses. Brothers of patients with sporadic prostate cancer aged < 55 years at onset were included as well.