Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the first report of a genome-wide scan for hereditary prostate cancer (HPCA hereinafter) in 1996, several publications have presented data implicating various chromosomal regions by linkage analysis without any consequential identifications of the target genes. The most intensive attention has been focused on chromosome 1, and it has been proposed to contain at least three sub-chromosomal regions (HPC1, PCAP, CAPB) harboring putative prostate cancer susceptibility genes. Nevertheless, one susceptibility gene, ELAC2/HPC2 at chromosome 17, has now been identified. Yet it seems to have a questionable role in prostate cancer predisposition. HPCA susceptibility loci have become undeniable archenemies of prostate cancer investigators, as the results of candidate gene analyses have been bewilderingly inconclusive. Predisposition to prostate cancer is most likely to be caused by several genes, different models of Mendelian inheritance, incomplete penetrance and varying population ethnicity frequencies. We will review the current state of the HPCA field and discuss the difficulties associated with identifying prostate cancer susceptibility genes.
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PMID:Prostate cancer susceptibility genes: many studies, many results, no answers. 1208 59

We encountered two pedigrees of hereditary prostate cancer. In one family, the father and his two sons had prostate cancer, and in the other family, three brothers developed prostate cancer. The mean age of these six individuals at the first examination was 65.3 years. Two individuals had stage B disease; three individuals, stage D disease; and one individual, disease of unknown stage. Histopathologically, two, one, and three individuals had well-, moderately, and poorly differentiated adenocarcinoma, respectively. As of September 28,2000, five of the six individuals were still alive. In a search of the literature, these were found to be the seventh and eighth pedigrees in Japan that met the criteria of hereditary prostate cancer proposed by Carter and colleagues in 1993.
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PMID:Two pedigrees of hereditary prostate cancer. 1210 21

HPC1/RNASEL was recently identified as a candidate gene for hereditary prostate cancer. We identified a novel founder frameshift mutation in RNASEL, 471delAAAG, in Ashkenazi Jews. The mutation frequency in the Ashkenazi population, estimated on the basis of the frequency in 150 healthy young women, was 4% (95% confidence interval [CI] 1.9%-8.4%). Among Ashkenazi Jews, the mutation frequency was higher in patients with prostate cancer (PRCA) than in elderly male control individuals (6.9% vs. 2.4%; odds ratio = 3.0; 95% CI 0.6-15.3; P=.17). 471delAAAG was not detected in the 134 non-Ashkenazi patients with PRCA and control individuals tested. The median age at PRCA diagnosis did not differ significantly between the Ashkenazi carriers and noncarriers included in our study. However, carriers received diagnoses at a significantly earlier age, compared with patients with PRCA who were registered in the Israeli National Cancer Registry (65 vs. 74.4 years, respectively; P<.001). When we examined two brothers with PRCA, we found a heterozygous 471delAAAG mutation in one and a homozygous mutation in the other. Loss of heterozygosity was demonstrated in the tumor of the heterozygous sib. Taken together, these data suggest that the 471delAAAG null mutation is associated with PRCA in Ashkenazi men. However, additional studies are required to determine whether this mutation confers increased risk for PRCA in this population.
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PMID:A novel founder mutation in the RNASEL gene, 471delAAAG, is associated with prostate cancer in Ashkenazi Jews. 1264 Oct 87

Deletions on human chromosome 8p22-23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC) have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in several processes proposed to be relevant to prostate carcinogenesis. Here we report the results of genetic analyses that indicate that mutations in MSR1 may be associated with risk of prostate cancer. Among families affected with HPC, we identified six rare missense mutations and one nonsense mutation in MSR1. A family-based linkage and association test indicated that these mutations co-segregate with prostate cancer (P = 0.0007). In addition, among men of European descent, MSR1 mutations were detected in 4.4% of individuals affected with non-HPC as compared with 0.8% of unaffected men (P = 0.009). Among African American men, these values were 12.5% and 1.8%, respectively (P = 0.01). These results show that MSR1 may be important in susceptibility to prostate cancer in men of both African American and European descent.
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PMID:Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. 1264 Oct 86

The candidate prostate cancer susceptibility gene HPC2/ELAC2 has two common coding polymorphisms: (Ser-->Leu 217) and (Ala-->Thr 541). The Thr541 variant in the HPC2/ELAC2 gene has previously been reported to be at an increased frequency in prostate cancer cases. To evaluate this hypothesis we genotyped 432 prostate cancer patients (including 262 patients diagnosed <or=55 years) and 469 UK, population based control individuals with no family history of cancer. We found no significant difference in the frequencies of Thr541-containing genotypes between cases and controls (OR=1.41, 95% CI 0.79-2.50). The association remained non-significant when the analysis was restricted to cases divided by age of onset into those diagnosed <or=55 years (OR=1.50, 95% CI 0.79-2.85) or to patients diagnosed >55 years (OR=1.27, 95% CI 0.59-2.74). We conclude that any association between the Thr541 variant and prostate cancer is likely to be weak.
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PMID:HPC2/ELAC2 polymorphisms and prostate cancer risk: analysis by age of onset of disease. 1237 7

The 8p22 through p23 region has been identified as a potential site for genes associated with prostate cancer. The gene LZTS1 has been mapped to the 8p22 through p23 region and identified as a potential tumor suppressor based on loss of heterozygosity studies using primary esophageal tumors. Sequence analysis of mRNA from various tumors has revealed multiple mutations and aberrant mRNA transcripts. The most recent report associates LZTS1 function with stabilization of p34(cdc2) during the late S-G2/M stage of mitosis, affecting normal cell growth. In this study, a detailed DNA sequence analysis of LZTS1 was performed in a screening panel consisting of sporadic and hereditary prostate cancer (HPC) cases and unaffected controls. Twenty-four SNP, 15 of which were novel, were identified in germline DNA. Four coding SNP were identified. Eleven informative SNP were genotyped in 159 HPC probands, 245 sporadic prostate cancer cases, and 222 unaffected controls. Four of these SNP were statistically significant for association with prostate cancer (P < or = 0.04). These results add evidence supporting a role of LZTS1 in prostate cancer risk.
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PMID:Germline sequence variants of the LZTS1 gene are associated with prostate cancer risk. 1237 6

To test the hypothesis that variation in the putative prostate cancer susceptibility gene ELAC2 contributes to the elevated risk of prostate cancer in Afro-Caribbean males from Tobago, we genotyped the S217L and A514T polymorphisms, previously reported to be associated with prostate cancer risk in a large sample of cases and controls. The frequency of the high-risk Leu allele at the S217L site was the same in cases and controls. Both cases and controls were homozygous for the low-risk Ala allele at the A514T site. In addition, we sequenced the exons and 3'- and 5'-flanking regions of ELAC2 in 24 individuals with histologically confirmed prostate cancer. We identified 17 new single nucleotide polymorphisms. An A(-1196)T polymorphism, which alters a predicted TATA box consensus sequence, was tested in cases and controls, and no significant difference in allele or genotype frequencies was observed. The absence of ELAC2 mutations and lack of association between polymorphisms in ELAC2 and prostate cancer in cases and controls leads us to conclude that ELAC2 does not contribute significantly to the elevated prevalence of prostate cancer in Afro-Caribbean males of Tobago.
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PMID:ELAC2 and prostate cancer risk in Afro-Caribbeans of Tobago. 1238 82

RNASEL (encoding ribonuclease L) has recently been proposed as a candidate for the hereditary prostate cancer (HPC1) gene. We determined that the RNASEL variant Arg462Gln has three times less enzymatic activity than the wildtype and is significantly associated with prostate cancer risk (P = 0.007). At least one copy of the mutated allele that causes this substitution is carried by nearly 60% of the men in our study. Men that are heterozygous with respect to the mutated allele have 50% greater risk of prostate cancer than non-carriers, and homozygotes have more than double the risk.
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PMID:RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases. 1264 Oct 88

Rare germline mutations of macrophage scavenger receptor 1 (MSR1) gene were reported to be associated with prostate cancer risk in families with hereditary prostate cancer (HPC) and in patients with non-HPC (Xu et al. 2002). To further evaluate the role of MSR1 in prostate cancer susceptibility, at Johns Hopkins Hospital, we studied five common variants of MSR1 in 301 patients with non-HPC who underwent prostate cancer treatment and in 250 control subjects who participated in prostate cancer-screening programs and had normal digital rectal examination and PSA levels (<4 ng/ml). Significantly different allele frequencies between case subjects and control subjects were observed for each of the five variants (P value range.01-.04). Haplotype analyses provided consistent findings, with a significant difference in the haplotype frequencies from a global score test (P=.01). Because the haplotype that is associated with the increased risk for prostate cancer did not harbor any of the known rare mutations, it appears that the observed association of common variants and prostate cancer risk are independent of the effect of the known rare mutations. These results consistently suggest that MSR1 may play an important role in prostate carcinogenesis.
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PMID:Common sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. 1247 93

Molecular genetic mechanisms involved in the progression of prostate cancer are not well understood due to extensive tumor heterogeneity and lack of suitable models. New methods such as fluorescence in-situ hybridization (FISH), comparative genomic hybridization (CGH) and microsatellite analysis have documented losses or gains on various chromosomes. Altered chromosomal regions have been associated with the activation of oncogenes and the inactivation of tumor suppressor genes or defects in mismatch repair (MMR) genes. It is suggested that increased genomic instability is associated with decreased androgen-responsive and progressive behavior of human prostate tumors, but it remains unclear whether this genomic instability is causing the progression of cancer or is the consequence of cancer. Extended studies on hereditary prostate cancer have identified 7 prostate cancer susceptibility loci on several chromosomes, but no specific gene has been confined for a large proportion of susceptibility. In this review we summarize the ongoing molecular genetic events associated with the sporadic and hereditary prostate cancer development and progression.
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PMID:Current status of the molecular genetics of human prostatic adenocarcinomas. 1247 10


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