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)

Linkage of a putative prostate cancer-susceptibility locus (HPC1) to chromosome 1q24-25 has recently been reported. Confirmation of this linkage in independent data sets is essential because of the complex nature of this disease. Here we report the results of a linkage analysis using 10 polymorphic markers spanning approximately 37 cM in the region of the putative HPC1 locus in 49 high-risk prostate cancer families. Data were analyzed by use of two parametric models and a nonparametric method. For the parametric LOD-score method, the first model was identical to the original report by Smith and coworkers ("Hopkins"), and the second was based on a segregation analysis previously reported by Carter and coworkers ("Seattle"). In both cases, our results do not confirm the linkage reported for this region. Calculated LOD scores from the two-point analysis for each marker were highly negative at small recombination fractions. Multipoint LOD scores for this linkage group were also highly negative. Additionally, we were unable to demonstrate heterogeneity within the data set, using HOMOG. Although these data do not formally exclude linkage of a prostate cancer-susceptibility locus at HPC1, it is likely that other prostate cancer-susceptibility loci play a more critical role in the families that we studied.
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PMID:Linkage analysis of 49 high-risk families does not support a common familial prostate cancer-susceptibility gene at 1q24-25. 931 39

In a recent study of 91 families having at least three first degree relatives with prostate cancer, we reported the localization of a major susceptibility locus for prostate cancer (HPC1) to chromosome 1 [band q24; J. R. Smith et al., Science (Washington DC), 274: 1371-1373, 1996]. There was significant evidence for locus heterogeneity, with an estimate of 34% of the families being linked to this locus. In this report, we investigate the importance of age at diagnosis of prostate cancer and number of affected individuals within a family as variables in the linkage analysis of an expanded set of markers on 1q24. Under two different models for the prostate cancer locus, we find that the evidence for linkage to HPC1 is provided primarily by large (five or more members affected) families with an early average age at diagnosis. Specifically, for 40 North American families with an average age at diagnosis <65 years, the multipoint lod score is 3.96, whereas for 39 families with an older average age at diagnosis, this value is -0.84. Assuming heterogeneity, the proportion of families linked is 66% for the 14 families with the earliest average ages at diagnoses, but it decreases to 7% for the families with the latest ages at diagnoses. A similar age effect is observed in 12 Swedish pedigrees analyzed. To test the hypotheses generated by these analyses, we examined an additional group of 13 newly identified prostate cancer families. Overall, these families provided additional evidence for linkage to this region (nonparametric linkage Z = 1.91; P = 0.04 at marker D1S1660), contributed primarily by the families in this group with early age at diagnosis [nonparametric linkage Z = 2.50 (P = 0.01) at D1S422]. These results are consistent with the existence of a locus in this region that predisposes men to develop early-onset prostate cancer.
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PMID:Early age at diagnosis in families providing evidence of linkage to the hereditary prostate cancer locus (HPC1) on chromosome 1. 935 26

New human prostate cell lines were developed from prostatic carcinoma (BRF-41T) and BPH (BRF-55T). Primary cultures were initiated from cellular outgrowths of explanted tissues. A serum-free medium, BRFF-HPC1, was developed for growing human prostatic cancer cells. Cell strains were immortalized with pRSV-T plasmid to generate permanent cell lines that exhibited an epithelial morphology. Both cell lines expressed the epithelial cell markers, cytokeratins 8 and 18 as well as the prostatic marker, PSA, and the androgen receptor gene. They possess the H-ras, K-ras, and p53 genes. We hope that these new human prostatic cell lines will be useful as in vitro models for cancer research.
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PMID:Establishment and characterization of immortalized human cell lines from prostatic carcinoma and benign prostatic hyperplasia. 945 47

Prostate cancer shows evidence of familial aggregation, particularly at young ages at diagnosis, but the inherited basis of familial prostate cancer is poorly understood. Smith et al. recently found evidence of linkage to markers on 1q, at a locus designated "HPC1," in 91 families with multiple cases of early-onset prostate cancer. Using both parametric and nonparametric methods, we attempted to confirm this finding, in 60 affected related pairs and in 76 families with three or more cases of prostate cancer, but we found no significant evidence of linkage. The estimated proportion of linked families, under a standard autosomal dominant model, was 4%, with an upper 95% confidence limit of 31%. We conclude that the HPC1 locus is responsible for only a minority of familial prostate cancer cases and that it is likely to be most important in families with at least four cases of the disease.
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PMID:Linkage analysis of chromosome 1q markers in 136 prostate cancer families. The Cancer Research Campaign/British Prostate Group U.K. Familial Prostate Cancer Study Collaborators. 949 42

Subsets of patients with common cancers belong to families in which the predisposition is inherited in a regular Mendelian fashion. Genes underlying these cancers are now recognized in colorectal cancer (APC, mismatch repair genes, LKB1) and in breast cancer (BRCA1, BRCA2) whereas, in prostate cancer, a locus in chromosome 1 (HPC1) has been proposed on the basis of linkage analysis. Major challenges are to determine the population incidence of these mutations, their penetrance, phenotypic expression, and the effects of modifier genes and epigenetic factors. Finally, the role of encoded proteins in carcinogenesis is a matter of major interest.
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PMID:The genetics of hereditary common cancers. 969 Sep 90

Over 200,000 new prostate cancer cases are diagnosed in the United States each year, accounting for more than 35% of all cancer cases affecting men, and resulting in 40,000 deaths annually. Attempts to characterize genes predisposing to prostate cancer have been hampered by a high phenocopy rate, the late age of onset of the disease and, in the absence of distinguishing clinical features, the inability to stratify patients into subgroups relative to suspected genetic locus heterogeneity. We previously performed a genome-wide search for hereditary prostate cancer (HPC) genes, finding evidence of a prostate cancer susceptibility locus on chromosome 1 (termed HPC1; ref. 2). Here we present evidence for the location of a second prostate cancer susceptibility gene, which by heterogeneity estimates accounts for approximately 16% of HPC cases. This HPC locus resides on the X chromosome (Xq27-28), a finding consistent with results of previous population-based studies suggesting an X-linked mode of HPC inheritance. Linkage to Xq27-28 was observed in a combined study population of 360 prostate cancer families collected at four independent sites in North America, Finland and Sweden. A maximum two-point lod score of 4.60 was observed at DXS1113, theta=0.26, in the combined data set. Parametric multipoint and non-parametric analyses provided results consistent with the two-point analysis. Significant evidence for genetic locus heterogeneity was observed, with similar estimates of the proportion of linked families in each separate family collection. Genetic mapping of the locus represents an important initial step in the identification of an X-linked gene implicated in the aetiology of HPC.
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PMID:Evidence for a prostate cancer susceptibility locus on the X chromosome. 977 11

A recent report has provided strong evidence for a major prostate cancer susceptibility locus (HPC1) on chromosome 1q24-25 (Smith et al, 1996). Most inherited cancer susceptibility genes function as tumour-suppressor genes (TSGs). Allelic loss or imbalance in tumour tissue is often the hallmark of a TSG. Studies of allelic loss have not previously implicated the chromosomal region 1q24-25 in prostate cancer. However, analysis of tumour DNA from cases in prostate cancer families has not been reported. In this study, we have evaluated DNA from tissue obtained from small families [3-5 affected members (n = 17)], sibling pairs (n = 15) and sporadic (n = 40) prostate tumours using the three markers from Smith et al (1996) that defined the maximum multipoint linkage lod score. Although widely spaced (12-50 cM), each marker showed evidence of allelic imbalance in only approximately 7.5% of informative tumours. There was no difference between the familial and sporadic cases. We conclude that the incidence of allelic imbalance at HPC1 is low in both sporadic tumours and small prostate cancer families. In this group of patients, HPC1 is unlikely to be acting as a TSG in the development of prostate cancer.
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PMID:Allelic imbalance in familial and sporadic prostate cancer at the putative human prostate cancer susceptibility locus, HPC1. CRC/BPG UK Familial Prostate Cancer Study Collaborators. Cancer Research Campaign/British Prostate Group. 983 74

The recognition that family history is an important risk factor for the development of prostate cancer has led to the search for prostate cancer susceptibility genes. Although most prostate cancer linkage studies have focused on Caucasian families, there is epidemiological evidence indicating that the relative risk attributable to a positive family history is similar in African-American and Caucasian-American families. There are data to support the existence of two potential prostate cancer susceptibility genes both on the long arm of chromosome 1; these have been called HPC1 and HPC2. Studies from us and others have shown that HPC1 may contribute to the clustering of prostate cancer in some African-American families. African-American families with multiple cases of prostate cancer should be encouraged to participate in genetic research studies with the goal of identifying the molecular basis for inherited prostate cancer susceptibility in this population.
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PMID:Hereditary prostate cancer in African-American families. 985 26

Prostate cancer clusters in some families, and an estimated 5%-10% of all cases are estimated to result from inheritance of prostate cancer-susceptibility genes. We previously reported evidence of linkage to the 1q24-25 region (HPC1) in 91 North American and Swedish families each with multiple cases of prostate cancer (Smith et al. 1996). In the present report we analyze 40 (12 original and 28 newly identified) Swedish families with hereditary prostate cancer (HPC) that, on the basis of 40 markers spanning a 25-cM interval within 1q24-25, have evidence of linkage. In the complete set of families, a maximum two-point LOD score of 1.10 was observed at D1S413 (at a recombination fraction [theta] of.1), with a maximum NPL (nonparametric linkage) Z score of 1.64 at D1S202 (P=.05). The evidence of linkage to this region originated almost exclusively from the subset of 12 early-onset (age <65 years) families, which yielded a maximum LOD score of 2.38 at D1S413 (straight theta=0) and an NPL Z score of 1.95 at D1S422 (P=.03). Estimates from heterogeneity tests suggest that, within Sweden, as many as 50% of early-onset families had evidence of linkage to the HPC1 region. These results are consistent with the hypothesis of linkage to HPC1 in a subset of families with prostate cancer, particularly those with an early age at diagnosis.
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PMID:In Swedish families with hereditary prostate cancer, linkage to the HPC1 locus on chromosome 1q24-25 is restricted to families with early-onset prostate cancer. 1036 25

A prostate cancer susceptibility locus ( HPC1 ) at 1q24-25 has been identified. Subsequent analysis showed that the majority of the evidence for localization was provided by families with relatively young (<65 years) average age at diagnosis. We examined evidence for linkage to this region in a set of 41 extended multi-case prostate cancer pedigrees containing 440 prostate cancer cases. Genotyping of five short tandem repeat markers in the region was performed on DNA from 1724 individuals, including 284 prostate cancer cases. In comparison with the families reported in the initial localization, the Utah pedigrees are generally much larger (average of 10.7 versus 5.1 cases) and have an older average age at diagnosis (69 versus 65 years). Two- and three-point linkage analyses were conducted using a previously reported model and provided replication for HPC1 (two-point: LOD = 1.73, P = 0.005 at D1S196; three-point: LOD = 2.06, P = 0.002 for the interval D1S196-D1S416 ). The youngest quartile (by median age at diagnosis) yielded a maximum LOD of 2.82, P = 0. 0003 (at D1S215-D1S222 ), compared with a maximum LOD of 0.73, P = 0. 07 for the oldest quartile pedigrees at the same locus. Further analysis with an age-dependent model, specifying higher sporadic rates for older cases, suggests that the linkage evidence may be lower than expected given the power of the resource due to a high sporadic rate in the large Utah pedigrees.
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PMID:Prostate cancer susceptibility locus HPC1 in Utah high-risk pedigrees. 1055 91


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