Cancer Report

Cancer : Prostate tumors
Summary
Cancer Name Prostate tumors
Description "Prostate cancer is the most commonly diagnosed type of cancer in men and a disease that is frequently diagnosed in advanced stages due to the lack of symptoms in early-stage prostate cancer. There are several widely accepted risk factors, including age, ethnicity, and family history."
 
Clinics and Pathology
 
Related Genes
Gene Symbol STAT3
Description From OMIM: "Yuan et al. (2005) showed that in response to cytokine treatment, STAT3 is acetylated on a single lysine residue, lys685. Histone acetyltransferase p300 (602700)-mediated STAT3 acetylation on lys685 was reversible by type I histone deacetylase (see 605314). Using a prostate cancer cell line that lacks STAT3, they established cell lines expressing wildtype STAT3 or a STAT3 mutant containing a lys685-to-arg substitution. Their findings showed that lys685 acetylation was critical for STAT3 to form stable dimers required for cytokine-stimulated DNA binding and transcriptional regulation, to enhance transcription of cell growth-related genes, and to promote cell cycle progression in response to treatment with oncostatin M (165095)."
 
Gene Symbol ATBF1
Description From OMIM: "The long arm of chromosome 16 is frequently deleted in human cancers. Sun et al. (2005) presented evidence that the ATBF1 gene is a good candidate for the 16q22 tumor suppressor gene. They narrowed the region of deletion at 16q22 to 861 kb containing ATBF1. ATBF1 mRNA was abundant in normal prostates but more scarce in approximately half of prostate cancers tested. In 24 of 66 (36%) cancers examined, Sun et al. (2005) identified 22 unique somatic mutations (see 104155.0001), many of which impaired ATBF1 function. Furthermore, ATBF1 inhibited cell proliferation. Sun et al. (2005) concluded that loss of ATBF1 is one mechanism that defines the absence of growth control in prostate cancer."
 
Gene Symbol ELAC2
Description from NCI: "The ELAC2/HPC2 prostate cancer predisposition gene on chromosome 17p was cloned after a genome-wide scan of high-risk families from Utah (Table 3). Two segregating germline mutations were identified among these multiplex prostate cancer families. Neither linkage evidence to 17p11 markers nor rare ELAC2/HPC2 variants were found in other sets of multiplex families. The ELAC2/HPC2 gene from 300 men from 150 prostate cancer families (with 3 or more cases of prostate cancer) was sequenced and identified only one stop codon and 5 additional missense mutations. Two common variants in ELAC2/HPC2 have been extensively studied for their potential contribution to prostate cancer susceptibility. In a clinic-based study of 350 prostate cancer cases and 266 age-matched and race-matched controls, it was reported that men who carry both of 2 common polymorphisms in the ELAC2/HPC2 gene experience a modest increase in risk of prostate cancer (OR = 2.4; 95% CI, 1.1¨C5.3). Many additional studies have been reported, 6 of which have been pooled in a meta-analysis. The authors suggest that the use of unscreened controls in case-control studies results in the inclusion of a significant number of men with prostate cancer cases among subjects who are classified as controls. This misclassification error will bias association studies toward the null. In the ELAC2/HPC2 meta-analysis, if exclusion of data from association studies in which prostate cancer screening was performed in controls resulted in a positive association between the Thr541 substitution and prostate cancer risk (OR = 1.8; 95% CI, 1.2¨C2.7; P = .0029), then to the extent that misclassification bias is operating in this series, the reported OR may underestimate the strength of the observed association. Studies using population-based sampling might be expected to clarify the potential role of common ELAC2/HPC2 polymorphisms in prostate cancer. An Australian study found no significant association between ELAC2/HPC2 and prostate cancer. Furthermore, these authors pooled their new data with those from 7 published studies; their meta-analysis strengthened the conclusion that no association exists."
 
Gene Symbol RB1
Description From COSMIC:
 
Gene Symbol APC
Description From COSMIC:
 
Gene Symbol RNASEL
Description from NCI: "The results of a genome-wide scan of 91 high-risk prostate cancer families meeting the Hopkins criteria from the United States and Sweden suggested the presence of a major prostate cancer susceptibility locus at chromosome 1q24, designated HPC1. Assuming genetic heterogeneity (i.e., that it is likely that only a subset of these 91 families carry an HPC1 mutation), the odds favoring the presence of this gene are nearly 1 million to 1. The genetic evidence supporting the existence of HPC1 was confined to 35% of the 91 families. This subgroup was characterized clinically by having more than 5 affected family members and an average age at prostate cancer diagnosis younger than 65 years. Further analyses of families that are genetically linked to HPC1 revealed the characteristics of younger ange at diagnosis, higher tumor grade and more advabced stage at diagnosis."
 
Gene Symbol HPCX
Description From manul review:
 
Gene Symbol HPC3
Description from NCI: "Evidence for yet another prostate cancer susceptibility locus on chromosome 20, which has been termed HPC20, has been reported. In stratified analyses, the group of patients with the strongest evidence of linkage to this locus were the families with fewer than 5 family members affected with prostate cancer, a later average age at diagnosis, and no male-to-male transmission, a pattern distinctly different from that reported for HPC1. Some evidence of prostate cancer linkage to HPC20 has been observed in 2 independent sets of families, though the candidate genomic interval remains large; however, a combined linkage analysis of 1,234 pedigrees performed by the ICPCG failed to replicate linkage of hereditary prostate cancer to 20q13 markers. In this report, the original 158 Mayo families that were used to identify HPC20 had a maximum heterogeneity logarithm of the odd (LOD) score under a recessive model of 2.78 whereas the remaining 1,076 families has a maximum heterogeneity LOD score of 0.06 using the same model. These data suggest that if HPC20 truly exists, it may only account for a small fraction of all hereditary prostate cancers."
 
Gene Symbol PTENP1
Description From COSMIC, cancer gene census of CGP
 
Gene Symbol CDH1
Description From OMIM: Jonsson et al. (2004) demonstrated an association between the -160C/A promoter polymorphism (192090.0018) and risk of hereditary prostate cancer.
 
Gene Symbol BRCA1
Description From OMIM, NCI
 
Gene Symbol ETV1
Description From cancer gene census of CGP, NCI, OMIM
 
Gene Symbol FOXO3A
Description From OMIM: "Modur et al. (2002) found that both FKHRL1 and FKHR were highly expressed in normal prostate. They also noted that, in PTEN-deficient prostate carcinoma cell lines, FKHR and FKHRL1 were cytoplasmically sequestered and inactive, and expression of TRAIL (603598), a proapoptotic effector, was decreased. Further experimentation revealed that TRAIL is a direct target of FKHRL1. Modur et al. (2002) hypothesized that the loss of PTEN contributes to increased tumor cell survival through decreased transcriptional activity of FKHR and FKHRL1 followed by decreased TRAIL expression and apoptosis"
 
Gene Symbol EGFR
Description From COSMIC:
 
Gene Symbol FOXO1A
Description From OMIM: "Modur et al. (2002) found that both FKHR and FKHRL1 were highly expressed in normal prostate. They also noted that, in PTEN-deficient prostate carcinoma cell lines, FKHR and FKHRL1 were cytoplasmically sequestered and inactive, and expression of TRAIL (603598), a proapoptotic effector, was decreased. Modur et al. (2002) determined that TRAIL is a direct target of FKHRL1, and they hypothesized that the loss of PTEN contributes to increased tumor cell survival through decreased transcriptional activity of FKHR and FKHRL1 followed by decreased TRAIL expression and apoptosis."
 
Gene Symbol STK11
Description From COSMIC:
 
Gene Symbol K-RAS
Description From COSMIC:
 
Gene Symbol EPHB2
Description from NCI: "Many cancer susceptibility genes increase the risk for more than one type of malignancy. For example, BRCA1 mutations increase a woman¡¯s chance of developing both breast and ovarian cancer. In this regard, a set of prostate cancer families who have one or more cases of primary brain cancer was identified.[54] In this set of 12 families, prostate cancer linkage to 1p36 markers was observed. This hypothetical gene locus has been named CAPB. Loss of heterozygosity (LOH) of this same genetic region was previously observed in sporadic brain cancers, suggesting that there is a tumor suppressor gene in this genomic interval. Other groups have not consistently confirmed prostate cancer linkage to CAPB in families with both brain and prostate cancers.[42,55] Further, there is evidence for linkage to 1p36 in one study of 207 prostate cancer families, considering as affected only those individuals with prostate cancer. This was particularly evident in families with early-onset disease in which the prostate cancer was diagnosed before age 59 years.[55] This raises the possibility that CAPB mutations may contribute to prostate cancer in a site-specific manner."
 
Gene Symbol AZGP1
Description From Atlas of Genetics and Cytogenetics in Oncology and Haematology:
 
Gene Symbol PIM1
Description From OMIM: "Using cDNA microarrays, Dhanasekaran et al. (2001) examined gene expression profiles of more than 50 normal and neoplastic prostate specimens and 3 common prostate cancer cell lines. Signature expression profiles of normal adjacent prostate, benign prostatic hypertrophy, localized prostate cancer, and metastatic, hormone-refractory prostate cancer were determined. Dhanasekaran et al. (2001) established many associations between genes and prostate cancer. They assessed 2 of these genes, hepsin (142440), a transmembrane serine protease, and PIM1, a serine/threonine kinase, at the protein level using tissue microarrays consisting of over 700 clinically stratified prostate cancer specimens. Expression of hepsin and PIM1 proteins was significantly correlated with measures of clinical outcome"
 
Gene Symbol ERG
Description From cancer gene census of CGP, NCI
 
Gene Symbol TMPRSS2
Description From cancer gene census of CGP, OMIM
 
Gene Symbol CEBPA
Description From COSMIC:
 
Gene Symbol KLF6
Description From cancer gene census of CGP, NCI, OMIM
 
Gene Symbol CTNNB1
Description From COSMIC:
 
Gene Symbol HRAS
Description From COSMIC:
 
Gene Symbol N-RAS
Description From COSMIC:
 
Gene Symbol PIK3CA
Description From COSMIC:
 
Gene Symbol CBX4
Description from NCI: "The ELAC2/HPC2 prostate cancer predisposition gene on chromosome 17p was cloned after a genome-wide scan of high-risk families from Utah (Table 3). Two segregating germline mutations were identified among these multiplex prostate cancer families. Neither linkage evidence to 17p11 markers nor rare ELAC2/HPC2 variants were found in other sets of multiplex families. The ELAC2/HPC2 gene from 300 men from 150 prostate cancer families (with 3 or more cases of prostate cancer) was sequenced and identified only one stop codon and 5 additional missense mutations. Two common variants in ELAC2/HPC2 have been extensively studied for their potential contribution to prostate cancer susceptibility. In a clinic-based study of 350 prostate cancer cases and 266 age-matched and race-matched controls, it was reported that men who carry both of 2 common polymorphisms in the ELAC2/HPC2 gene experience a modest increase in risk of prostate cancer (OR = 2.4; 95% CI, 1.1¨C5.3). Many additional studies have been reported, 6 of which have been pooled in a meta-analysis. The authors suggest that the use of unscreened controls in case-control studies results in the inclusion of a significant number of men with prostate cancer cases among subjects who are classified as controls. This misclassification error will bias association studies toward the null. In the ELAC2/HPC2 meta-analysis, if exclusion of data from association studies in which prostate cancer screening was performed in controls resulted in a positive association between the Thr541 substitution and prostate cancer risk (OR = 1.8; 95% CI, 1.2¨C2.7; P = .0029), then to the extent that misclassification bias is operating in this series, the reported OR may underestimate the strength of the observed association. Studies using population-based sampling might be expected to clarify the potential role of common ELAC2/HPC2 polymorphisms in prostate cancer. An Australian study found no significant association between ELAC2/HPC2 and prostate cancer. Furthermore, these authors pooled their new data with those from 7 published studies; their meta-analysis strengthened the conclusion that no association exists."
 
Gene Symbol BRCA2
Description From NCI, OMIM
 
Gene Symbol CDKN2A
Description From COSMIC:
 
Gene Symbol TOPORS
Description From COSMIC:
 
Gene Symbol BRAF
Description From COSMIC:
 
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Source and Citation
Source NCI
Citation "NCI, URL:http://www.cancer.gov/cancertopics/types/prostate/"
URL http://www.cancer.gov/cancertopics/types/prostate/