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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently cancer susceptibility syndromes have been characterized that suggest possible genetic linkages between breast cancer and prostate cancer within families. Despite these connections, male breast cancer and prostate cancer in an individual man has rarely been reported. The clinical features of 10 patients with both of these cancers are described here. One hundred sixty-one patients with male breast cancer were seen at the Dana-Farber Cancer Institute and Massachusetts General Hospital between 1977 and 2000. Of these, 10 were identified who also had prostate cancer. A retrospective review of records from these 10 patients was performed. Breast cancer preceded prostate cancer in eight of these men. The mean age of diagnosis of breast cancer was 65.7 years (range 47-72 years). Twenty percent had nodal involvement at diagnosis and two patients ultimately developed evidence of metastatic disease. The mean age of diagnosis of prostate cancer was 68.0 years (range 51-76 years) with a median prostate-specific antigen (PSA) level at diagnosis of 6 ng/ml (range 1.8-47.5 ng/ml). Seven patients had a family history of female breast cancer in a first-degree relative, while one had a family history of prostate cancer. At a median follow-up of 6.5 years from initial cancer diagnosis, one patient had died of metastatic breast cancer and another had died of metastatic prostate cancer. The clinical features and course of the breast cancers diagnosed in this series do not appear significantly different from those described for the general population of male breast cancer patients. In addition, these men do not appear to develop prostate cancer at an earlier age or more aggressive stage than the general population.
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PMID:Male patients with diagnoses of both breast cancer and prostate cancer. 1275 29

In most developed countries, prostate cancer is the most frequently diagnosed malignancy in men. The extent to which the marked racial/ethnic difference in its incidence rate is attributable to screening methods, environmental, hormonal and/or genetic factors remains unknown. A positive family history is among the strongest epidemiological risk factors for prostate cancer. It is now well recognized that the role of candidate genetic markers to this multifactorial malignancy is more difficult to identify than the identification of other cancer susceptibility genes. Indeed, despite the localization of several susceptibility loci, there has been limited success in identifying high-risk susceptibility genes analogous to BRCA1 or BRCA2 for breast and ovarian cancer. Nonetheless, three strong candidate susceptibility genes have been described, namely ELAC2 (chromosome 17p11/HPC2 region), 2'-5'-oligoadenylate-dependent ribonuclease L (RNASEL), a gene in the HPC1 region, and Macrophage Scavenger Receptor 1 (MSR1), a gene within a region of linkage on chromosome 8p. Additional studies using larger cohorts are needed to fully evaluate the role of these susceptibility genes in prostate cancer risk. It is also of interest to mention that a significant percentage of men with early-onset prostate cancer harbor germline mutation in the BRCA2 gene thus confirming its role as a high-risk prostate cancer susceptibility gene. Although initial segregation analyses supported the hypothesis that a number of rare highly penetrant loci contribute to the Mendelian inheritance of prostate cancer, current experimental evidence better supports the hypothesis that some of the familial risks may be due to inheritance of multiple moderate-risk genetic variants. In this regard, it is not surprising that analyses of genes encoding key proteins involved in androgen biosynthesis and action led to the observation of a significant association between a susceptibility to prostate cancer and common genetic variants in some of those genes.
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PMID:Prostate cancer susceptibility genes: lessons learned and challenges posed. 1279 Jul 86

Actual uptake of genetic testing for cancer susceptibility is generally lower than 50%, despite a high initial interest above 80%. As population-based genetic testing for cancer susceptibility becomes more widespread, there will be an increasing need to understand the relationship of patient-affective factors to test intention and actual uptake behavior. Using hypothetical genetic testing for prostate cancer susceptibility as an example, we used surveys of 400 men in the general population of Philadelphia to develop a Structural Equation Modeling diagram to reveal the influence of affective factors implicated in the intention to undergo genetic testing for prostate cancer risk. Results showed that most men want genetic testing for prostate cancer, believe strongly in its benefits, and are not deterred by negative affect. Our data suggest that high positive expectations, plus a high desire to comply with physician and family suggestions, result in an increased test intention. Informed consent assessment, therefore, requires an appreciation not only of patient risk, but awareness of patient motivation and affect as well.
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PMID:Health motivation and emotional vigilance in genetic testing for prostate cancer risk. 1552 78

The tumor suppressor gene p53 and its downstream effector p21 are thought to play major roles in the development of human malignancy. Polymorphic variants of p53 at codon 72, and p21 at codon 31, have been found to be associated with cancer susceptibility, but few studies have investigated their effect on prostate cancer risk. In this case-control study, we investigated the association of p53 codon 72 and p21 codon 31 polymorphisms with prostate cancer risk in a Taiwanese population. In total, 200 patients with prostate cancer, 247 age-matched male controls, and 181 non-age-matched symptomatic benign prostatic hyperplasia (BPH; American Urological Association symptom score > or = 8 and prostate volume > 20 gm) recruited from two medical centers in southern Taiwan were genotyped. Overall, we found no significant association between p53 polymorphism and risk of prostate cancer. However, for p21 polymorphism, the frequencies of p21 Ser/Ser, Ser/Arg and Arg/Arg were 52 (26.0%), 85 (42.5%), 63 (31.5%) in case patients, 48 (26.5%), 82 (45.3%), 51 (28.2%) in BPH patients, and 76 (30.8%), 119 (48.2%), 52 (21.1%) in controls, respectively. Among the prostate cancer cases and controls, subjects with Arg/Arg genotype were found to have a 1.78-fold increased risk [95% confidence interval (CI), 1.06-3.01] of developing prostate cancer compared with those having the Ser/Ser genotype, after adjusting for other potential covariates. This significant association was slightly stronger [odds ratio (OR), 2.13; 95% CI, 1.16-3.92] in younger men (< or = 72 years; n = 99 and 126 for cases and controls, respectively) and correlated with localized disease stage (OR, 1.96; 95 % CI, 1.15-3.35) and moderately differentiated prostate cancer (OR, 2.04; 95% CI, 1.17-3.53). In addition, the Arg/Arg genotype was associated with BPH risk in those with large prostate volumes (> 50 mL) compared with those having the Ser/Ser genotype [OR, 2.29; 95% CI, 1.07-4.98]. Our findings suggest that the p21 codon 31 polymorphism may be associated with the development of prostate enlargement and cancer.
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PMID:p53 Codon 72 and p21 codon 31 polymorphisms in prostate cancer. 1559 83

Accumulation of information about genetics and epigenetics has accelerated research investigating the inherent individual variation in cancer susceptibility. Gene polymorphisms, in particular single nucleotide polymorphisms, are being evaluated for their role in various cancers including prostate cancer. Especially, polymorphisms of hormone-related genes such as steroid-hormone receptors in prostate cancer have been recently focused and used in molecular epidemiology. In this article, we present data from the molecular epidemiology about Japanese prostate cancer using polymorphisms of hormone-related genes and offer suggestions for further research.
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PMID:[Polymorphisms of hormone-related genes and prostate cancer risk in Japan]. 1571 69

To identify genes that generally increase the risk of cancer, we performed a systematic search throughout the genome in 188 families primarily ascertained for prostate cancer but which also included individuals with other cancers. We observed significant evidence for linkage between susceptibility to all cancers and markers at 3p24, with a peak HLOD of 3.08 (P=0.0002). Compared to families with less than three other cancers and prostate cancer only, evidence for linkage at this region was stronger among families with at least three other cancers. This is the first reported example of a genome-wide search for general cancer susceptibility genes among hereditary prostate cancer families.
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PMID:Evidence for a general cancer susceptibility locus at 3p24 in families with hereditary prostate cancer. 1572 17

To investigate the role of genetics in the development of cancer, we developed a new approach to analyze data on prostate, breast, and colorectal cancer from the Swedish, Danish, and Finnish twin registries on monozygotic (MZ) and same-sex dizygotic (DZ) twins. In the spirit of a sensitivity analysis, we modeled genetic inheritance as either an autosomal recessive or dominant cancer susceptibility (CS) genotype that involves either a single gene, many genes with equal allele frequencies, or three genes with a ninefold range of allele frequencies. We also modeled the joint probability of cancer incidence among five age categories, conditional on the presence or absence of the CS genotype. The main assumptions are: (1) The joint distribution of unobserved environmental effects in a twin pair conditional on the presence or absence of the CS genotype is the same for MZ and DZ twins, (2) the probability of cancer conditional on the presence or absence of the CS genotype and the unobserved environmental effects (i.e., the gene-environment interaction) is the same for MZ and DZ twins, and (3) the probability of cancer is independent between twins with the CS genotype. Estimation was maximum likelihood via a search over allele frequency and two levels of EM algorithms. Models had acceptable or good fits. Variability was estimated using a bootstrap approach, but only 50 replications were feasible. The 94th percentile of bootstrap replications for the estimated fraction of cancers with the CS genotype ranged, over the various genetic models, from 0.16 to 0.45 for prostate cancer, 0.12 to 0.30 for breast cancer, and 0.08 to 0.27 for colorectal cancer. We conclude that genetic susceptibility makes only a small to moderate contribution to the incidence of prostate, breast, and colorectal cancer.
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PMID:Genetic susceptibility to prostate, breast, and colorectal cancer among Nordic twins. 1573 78

Inter-individual differences in cancer susceptibility may be mediated in part through polymorphic variability in the bioactivation and detoxification of carcinogens. The glutathione S-transferases (GSTs), which are active in detoxification of wide variety of carcinogens, have been consistently implicated as cancer susceptibility genes in this context. We here assessed the association of GSTM1 and GSTP1 polymorphisms with susceptibility to prostate cancer in a case-control study of 75 patients and 100 age-matched controls in a South Indian population. The GSTM1 null polymorphism was detected by PCR and the GSTP1 Ile105Val polymorphism by PCR-RFLP using peripheral blood DNA. There was no significant link between the null genotype of GSTM1 and risk of prostate cancer (OR-1.79; 95% CI-0.78-4.11; P-0.18). However, the GSTP1 Ile/Val genotype was significantly associated with a decreased risk for prostate cancer (OR-0.36; 95% CI-0.18-0.73; P<0.001). Analysis of the variant GSTM1 and GSTP1 genotypes in combination did not reveal any significant difference between cases and controls, even with a stratified analysis tumor grades. Thus our study indicates that the GSTP1 Ile/Val genotype may decrease risk of prostate cancer in the South Indian population.
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PMID:Polymorphisms at GSTM1 and GSTP1 gene loci and risk of prostate cancer in a South Indian population. 1623 91

Cytochrome P450 (CYP) 3A4 is responsible for most CYP3A-mediated drug metabolism but the minor isoforms CYP3A5, CYP3A7 and CYP3A43 also contribute. CYP3A5 is the best studied of the minor CYP3A isoforms. It is well established that only approximately 20% of livers express CYP3A5. The most common reason for the absence of expression is a splice site mutation. The frequency of variant alleles shows interethnic differences, with the wild-type CYP3A5*1 allele more common in Africans than Caucasians and Asians. In individuals who express CYP3A5, the percentage contributed to total hepatic CYP3A by this isoform is still unclear, with estimates ranging from 17% to 50%. CYP3A5 is also expressed in a range of extrahepatic tissues. Only limited information is available on the regulation of CYP3A5 expression but it appears to be inducible via the glucocorticoid receptor, pregnane X receptor and constitutive androstane receptor-beta, as for CYP3A4. Although information on the substrate specificity of CYP3A5 is limited compared with CYP3A4, there have been a number of recent pharmacokinetic studies on a small range of substrates in individuals of known genotype to investigate the contribution of CYP3A5. In the case of midazolam, ciclosporin, nifedipine and docetaxel, clearance by individuals with a CYP3A5-expressing genotype did not differ from that for nonexpressors, but in the case of tacrolimus, eight independent studies have demonstrated faster clearance by those carrying one or two CYP3A5*1 alleles. This may reflect faster turnover of tacrolimus by CYP3A5 than the other substrates. CYP3A5 genotype may affect cancer susceptibility. Certain combined CYP3A4/CYP3A5 haplotypes show differential susceptibility to prostate cancer and there is a nonsignificant increase in the risk of small-cell lung cancer for a CYP3A5*1/*1 genotype. Females positive for CYP3A5*1 appear to reach puberty earlier, which may affect breast cancer risk. CYP3A5*1 homozygotes may have higher systolic blood pressure.CYP3A7 is predominantly expressed in fetal liver but is also found in some adult livers and extrahepatically. The molecular basis for expression in adult liver relates to upstream polymorphisms, which appear to increase homology to CYP3A4 and make regulation of expression more similar. CYP3A7 has a specific role in hydroxylation of retinoic acid and 16alpha-hydroxylation of steroids, and is therefore of relevance both to normal development and carcinogenesis.CYP3A43 is the most recently discovered CYP3A isoform. In addition to a low level of expression in liver, it is expressed in prostate and testis. Its substrate specificity is currently unclear. Polymorphisms predicting absence of active enzyme have been identified.
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PMID:Significance of the minor cytochrome P450 3A isoforms. 1643 Mar 9

Genomic approaches to cancer are beginning to have an important impact in unraveling the complex etiologies of this disease, as well as allowing us to rationally treat afflicted patients. In this article, we will focus largely on genomic approaches to breast and prostate cancer susceptibility, as well as pharmacogenomic approaches to treatment. Current genomic approaches to cancer susceptibility have led to some significant, if not spectacular, successes which include breast cancer. More modest achievements, if not outright failures, such as in prostate cancer, are also notable and will be discussed further. We propose interdisciplinary approaches involving basic, clinical and population scientists to vigorously attack the cancer problem scientifically and with more organization. We highlight recent successes and suggest new approaches with a personal, if not provocative, perspective.
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PMID:Genomics in breast and prostate cancer: assessment of the current state and future perspectives. 1678 15


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