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)

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

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

Frequent loss of heterogeneity in prostate cancer cells and linkage studies of families affected by hereditary prostate cancer (HPC) have implied that the short arm of chromosome 8, specifically 8p22-23, may harbor a prostate-cancer-susceptibility gene. In a recent study, seven potentially important mutations in the macrophage scavenger receptor 1 gene (MSR1), located at 8p22, were observed in families affected with HPC, and an indication of co-segregation between these mutations and prostate cancer was reported. In an attempt to confirm linkage at 8p22-23, we performed linkage analyses in 57 families affected with HPC (ascertained throughout Sweden) by using 13 markers on the short arm of chromosome 8. In the complete set of families, evidence for prostate cancer linkage was observed at 8p22-23, with a peak hold of 1.08 (P=0.03), observed at D8S1731, approximately 1 cM centromeric to the MSR1 gene. At marker D8S1135, the closest marker to MSR1, a hlod of 1.07 (P=0.03) was observed. Evidence of linkage was seen in families with early-onset HPC and in families with a small number of affected individuals. The peak multipoint non-parametric linkage score was 2.01 (P=0.03) at D8S552 in the 14 pedigrees with mean age at onset <65 years, and 2.25 (P=0.01) at D8S1731 in the 36 pedigrees with fewer than five affected family members. Thus, we have confirmed evidence for prostate cancer linkage at 8p22-23. Follow-up studies to evaluate the possible association between prostate cancer and genes in this region, especially the MSR1 gene, are warranted.
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PMID:Linkage analysis of prostate cancer susceptibility: confirmation of linkage at 8p22-23. 1259 35

Both rare germ-line mutations and common sequence variants of the macrophage scavenger receptor 1 (MSR1) gene have recently been implicated as potential prostate cancer susceptibility factors. However, existing studies are limited by the referral-based nature of samples and a paucity of African-American participants. In this context, we evaluated the association of germ-line mutations and common MSR1 sequence variants with prostate cancer risk in a case control study of a community-based sample of 134 African-American men with prostate cancer and 340 unaffected controls. In our sample, the rare Asp174Tyr missense change was identified nearly twice as frequently in men with prostate cancer (6.8%) compared with unaffected controls (3.6%; P = 0.14). Moreover, significantly different allele frequencies between cases and controls were observed for one of the sequence variants, IVS5-59 (P = 0.02). Taken together, our results provide some additional support for the hypothesis that selected, rare MSR1 mutations are associated with increased prostate cancer susceptibility among African-American men.
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PMID:Germ-line mutations of the macrophage scavenger receptor 1 gene: association with prostate cancer risk in African-American men. 1283 31

The macrophage scavenger receptor 1 gene (MSR1) was recently identified as a candidate susceptibility gene for hereditary prostate cancer and as a risk factor for sporadic prostate cancer. To confirm these findings, we screened MSR1 for germline mutations among individuals with familial prostate cancer and tested gene variants for associations in both sporadic and familial prostate cancer. Our results do not support MSR1 as a risk factor for prostate cancer.
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PMID:No association of germline alteration of MSR1 with prostate cancer risk. 1295 98

The class A macrophage scavenger receptor (SR-A) is expressed in antigen presenting cells and is involved in host immune responses. Germ-line mutation of this gene has been associated with increased risk of human prostate cancer. However, there is little known about its expression in normal or neoplastic human prostate tissues. Double immunofluorescent labeling with monoclonal antibodies to SR-A and specific macrophage and dendritic cell markers was used to identify cells expressing SR-A in human prostate tissues. SR-A immunohistochemical staining was performed on paraffin sections of normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and prostate cancers from radical prostatectomy specimens. SR-A was expressed in a subset of macrophages and dendritic cells that infiltrated prostatic tissues. The majority of SR-A-positive cells coexpressed CD68, and a relatively low percentage expressed S100 protein. The number of SR-A-positive cells was significantly increased in PIN as compared with normal prostatic tissue (P = 0.0176). In contrast, the number of SR-A-positive cells decreased with tumor progression. A lower SR-A-positive cell density was associated with higher clinical stage (rho = -0.26; P = 0.0234). Inverse associations were also found between SR-A density and positive lymph nodes (rho = -0.23; P = 0.0437), tumor size (rho = -0.31; P = 0.0100) and preoperative PSA levels (rho = -0.32; P = 0.0057). SR-A density is a significant predictor of disease-free survival after surgery univariately (P = 0.0003), as well as multivariately, adjusted for known clinical and pathological markers including preoperative prostate-specific antigen, clinical stage, Gleason score, surgical margin, extraprostatic extension, and seminal vesicle invasion, as well as lymph node metastasis (P = 0.0021). The preferential accumulation of SR-A-positive cells in PIN suggests a role for SR-A in the APC response to early malignancy. A reduction in the number of SR-A-positive cells demarcates tumor progression as indicated by clinical and pathological correlations. Our results additionally indicate that systematic measurement of SR-A density is a strong prognostic marker for clinical outcome after surgery.
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PMID:Reduced infiltration of class A scavenger receptor positive antigen-presenting cells is associated with prostate cancer progression. 1502 46

Prostate cancer is one of the most common cancers among men and has long been recognized to occur in familial clusters. Identification of genetic susceptibility loci for prostate cancer has however been extremely difficult, and only in 1996 was the first prostate cancer susceptibility locus HPC1 mapped to chromosome 1q24-25. Since, several additional putative loci have been identified by genetic linkage analysis on chromosome 1, 17, 20 and X (reviewed in). For three of these loci, family-based studies have identified three genes associated with inherited prostate cancer: the 3' processing endoribonuclease ELAC2/HPC2 gene, the macrophage scavenger receptor 1 gene (MSR1), and the endoribonuclease RNase L gene (RNAse L/HPC1). Here we will focus our review on the RNAse L gene and its involvement in prostate cancer and other diseases.
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PMID:Involvement of the RNAse L gene in prostate cancer. 1686 93

Genetic susceptibility to prostate cancer has been consistently observed by a large number of studies. Recently, several pieces of evidence obtained from epidemiological and pathological studies support that chronic inflammation in prostate tissues may play a role in prostate cancer development. Multiple genes that play critical roles in inflammatory pathways have been associated with prostate cancer risk. In this article we review the key genetic findings of the associated genes. This includes 2 genes identified through family studies, ribonuclease L (RNASEL) and macrophage scavenger receptor 1 (MSR1), as well as a number of genes suggested by case-control studies, such as macrophage inhibitory cytokine-1 (MIC-1), interleukins (IL-8, IL-10), vascular endothelial growth factor (VEGF), intercellular adhesion molecule (ICAM), and Toll-like receptors (TLR-4, TLR-1-6-10 gene cluster). Overall, recent studies seem to suggest multiple genes work together to increase prostate risk, and this is consistent with the reality that inflammation is a very complex process. Thus, future studies are expected to place an emphasis on the study of gene-gene interactions. Advances in high throughput genotyping, data mining, and algorithm development are needed in order to produce interpretable results.
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PMID:Genetic variability in inflammation pathways and prostate cancer risk. 1748 24

Data from epidemiologic and twin studies suggest an important role of genetic susceptibility in prostate cancer. Variants of the macrophage scavenger receptor 1 (MSR1) gene have been linked to both hereditary and sporadic prostate cancer, although the evidence is inconclusive. Most studies have been conducted on Caucasians. The role of MSR1 in prostate cancer development among Asians, for whom rates of prostate cancer are low but rising rapidly, is unclear. To evaluate further the relationship between MSR1 variants and prostate cancer risk, we sequenced all the 11 MSR1 exons, exon-intron junctions, promoter regions, as well as 5' and 3' untranslated regions (UTRs) in 86 individuals from Shanghai, China. We identified a total of 21 sequence variants, including three novel variants that have not been reported previously. To balance genotyping cost and the capacity to capture sufficient genetic variation, we genotyped four haplotype-tagging variants (P275A, INDEL7, P346P and 3' UTR 70006), which capture 85% of the genetic variation in MSR1 in this population. These four variants, plus two other variants (PRO3 and INDEL1) that have been linked to prostate cancer risk in the previous studies, were typed for all study subjects, which included 130 prostate cancer cases, 130 patients with benign prostatic hyperplasia and 150 controls randomly selected from the population. Three of the six variants were associated with prostate cancer. Men with a P346P (a novel variant) G allele (AG + GG) had a significantly reduced risk of total prostate cancer [odds ratio = 0.47, 95% confidence interval (CI) 0.23-0.96], whereas those with a P275A G allele had a 37% reduced risk of prostate cancer (95% CI 0.39-1.02), with more pronounced reduction in risk seen for localized cancer cases (odds ratio = 0.25, 95% CI 0.12-0.52; P = 0.001). In addition, men with the INDEL7 variant had a 67% reduced risk of localized cancer (95% CI 0.16-0.68). Based on the four tagging variants, we inferred four major haplotypes that accounted for >90% of the haplotype variation in this population. The haplotype frequencies were significantly different between localized prostate cancer cases and controls, with a global P value of 0.004, and the haplotype containing the minor alleles of the P275A and INDEL7 variants was associated with a significantly reduced risk of localized prostate cancer (odds ratio = 0.28, 95% CI 0.13-0.59), relative to the most common haplotype. These results, although modest and confined mainly to localized prostate cancer, suggest that MSR1 polymorphisms may play a role in prostate cancer etiology in Chinese men. The role of MSR1 warrants further investigation in larger studies and other populations.
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PMID:MSR1 variants and the risks of prostate cancer and benign prostatic hyperplasia: a population-based study in China. 1776 78

Cancer-derived heat shock protein gp96 induces a tumor-specific protective immune response primarily mediated by cytotoxic T lymphocytes (CTL) directed toward cancer-associated peptides associated with gp96. Both innate and adaptive immune responses have been demonstrated using a cell culture-based signaling mechanism. When used as an extraneous vaccine, one critical interaction which must occur for an immune response to be generated is the interaction between gp96 and the antigen presenting cell (APC) surface receptors (CD91, SR-A, TLR-2, and TLR-4). Our previous study concluded that gp96 purified from various rat and human prostate cancers is differentially glycosylated based on the amino and neutral monosaccharide content, and it was postulated that the monosaccharides may play a role in its biological activity. In this report, we report differences in the cancer-specific sialic acid content of gp96 purified from normal rat prostate compared to two rat prostate cancers, MAT-LyLu and Dunning G, as well as between two human prostate cancer cells, LnCaP and DU145. We also examined the modulatory effect of sialic acid residues on the binding of gp96 to APCs and its subsequent activation. Our results supported the contention that significant differences in the sialic acid content exist between Dunning G, MAT-LyLu, and normal rat prostate gp96, which affected its binding and biochemical activity to APCs. We therefore postulate that varied glycans of HPS96, a hitherto neglected structural component, may play a pivotal role in its anticancer activity. We suggest that construction of the glycan tree is a key to identification of the necessary and sufficient elements in the structure-function activity of HSP96.
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PMID:Sialic acid content of tissue-specific gp96 and its potential role in modulating gp96-macrophage interactions. 1957 60


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