RÉSUMÉ
The retinoic acid receptor (RAR) beta gene is a putative tumor suppressor gene on chromosome 3p24, where a high incidence of loss of heterozygosity is detected in many types of tumors. Retinoic acid suppresses cancer cell growth through binding to RARs, especially RARbeta, indicating a critical role in mediating anticancer effects. Selective loss or down-regulation of RARbeta mRNA and protein has been reported in prostate cancers (PCas), although the mechanisms remain unclear. We investigated the role of epigenetic modification in RARbeta2 gene silencing. Aberrant methylation was detected in 11 of 14 (79%) primary PCas, 9 of 10 (90%) hormone-refractory PCas, and 2 of 4 (50%) PCa cell lines, but not in any normal prostate samples. Chromatin immunoprecipitation assay showed that all RARbeta2-negative cells (LNCaP, PC3, and DU145) were hypoacetylated at both histones H3 and H4. After exposure to 5-aza-2prime;-deoxycytidine treatment, Trichostatin A and all-trans retinoic acid induced partial demethylation, increased accumulation of acetylated histones, and markedly restored the expression of RARbeta2 in RARbeta2-negative cells. These data suggest that the RARbeta2 gene may be one of the frequently silenced genes by epigenetic modifications in PCa.
Sujet(s)
Tumeurs de la prostate/génétique , Récepteurs à l'acide rétinoïque/génétique , Séquence nucléotidique , Méthylation de l'ADN , ADN tumoral , Antienzymes/pharmacologie , Inhibiteurs de désacétylase d'histone , Humains , Mâle , Données de séquences moléculaires , Régions promotrices (génétique) , RT-PCRRÉSUMÉ
Steroid hormones, especially testosterone, play important roles in the carcinogenesis of prostate cancer, and several studies have reported changes in risk with polymorphisms of genes involved in steroid metabolism. One example is the CYP17 gene, which has a polymorphic T-to-C substitution in the 5'-untranslated region giving rise to A1 (T) and A2 (C) alleles. Steroid 5alpha-reductase type II (SRD5A2), which converts testosterone to the metabolically more active dihydrotestosterone, exhibits 2 polymorphisms: V89L, which substitutes leucine for valine at codon 89, and A49T, which substitutes threonine for alanine at codon 49. We therefore designed a case-control study of 105 prostate-cancer patients and 210 controls with benign prostatic hyperplasia for the purpose of investigating the association between prostate-cancer risk and polymorphisms in the SRD5A2 and CYP17 genes among the Japanese. The frequency of the CYP17 A2/A2 genotype in cases (18.8%) was higher than in controls (14.5%). Compared with the A1/A1 genotype, the odds ratio for the A2/A2 genotype was 2.39 (95% confidence interval 1.04-5.46, p = 0.04). The frequency of the SRD5A2 LL genotype in cases (29.3%) was also slightly higher than in controls (24.6%), but this was not significant. Regarding the A49T polymorphism of SRD5A2, we could not detect the T allele in any of the examined samples. These data suggest a significant association between the CYP17 polymorphism and prostate-cancer risk among the Japanese.
Sujet(s)
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/génétique , Polymorphisme génétique , Tumeurs de la prostate/génétique , Steroid 17-alpha-hydroxylase/génétique , Adulte , Facteurs âges , Sujet âgé , Allèles , Génotype , Humains , Mâle , Adulte d'âge moyen , Tumeurs de la prostate/enzymologie , Tumeurs de la prostate/étiologie , RisqueRÉSUMÉ
Associations between genetic polymorphisms of CYP1A1, CYP1A2, CYP2E1, GSTM1 and GSTT1 and prostate cancer (PCa) were analyzed in a case-control study of 315 individuals. The frequency of valine (Val)/valine (Val) genotypes for CYP1A1 was 11.3% in cases compared with 5.5% in controls, this polymorphism thus being associated with a significantly increased risk of PCa (odds ratio=2.4, 95% confidence interval (CI)=1.01-5.57). No links were detected between PCa and polymorphisms in other enzymes. However, the combination of CYP1A1 (Ile/Val and/or Val/Val) polymorphisms with the GSTM1 null type resulted in an OR of 2.2 (CI=1.10-4.57, 1.12-4.20, respectively). This study suggests that the CYP1A1 polymorphism and its combination with GSTM1 may be associated with PCa susceptibility in the Japanese population.
Sujet(s)
Cytochrome P-450 CYP1A1/génétique , Cytochrome P-450 CYP1A2/génétique , Cytochrome P-450 CYP2E1/génétique , Prédisposition génétique à une maladie , Glutathione transferase/génétique , Polymorphisme génétique , Tumeurs de la prostate/génétique , Études cas-témoins , Génotype , Humains , Japon , Mâle , Odds ratio , Facteurs de risqueRÉSUMÉ
We analyzed K-ras and p53 mutations, microsatellite instability (MSI), and loss of heterozygosity (LOH) using the polymerase chain reaction (PCR) methods, as well as p53 expression and the Ki-67 labeling index (LI) using immunohistochemistry in 10 duodenal and 10 jejunal/ileal carcinomas. K-ras mutations were detected in two duodenal (20%) and three jejunal/ileal (30%) carcinomas and p53 mutations in one (10%) and three (30%), respectively. LOH of 17p was detected in two duodenal (20%) and two jejunal/ileal (20%) carcinomas and p53 expression in four duodenal (40%) and four jejunal/ileal (40%). One duodenal (10%) and two jejunal/ileal (20%) carcinomas demonstrated MSI. LOH of APC was detected in three jejunal/ileal (30%), but none of the duodenal carcinomas. The Ki-67 LI was 44% in duodenal and 52.6% in jejunal/ileal carcinomas. A subset of small intestinal carcinomas showed involvement of K-ras and p53 mutations, LOH of APC, and MSI. A difference was also apparent for LOH of APC between duodenal and jejunal/ileal carcinomas.
Sujet(s)
Division cellulaire/génétique , Transformation cellulaire néoplasique/génétique , Aberrations des chromosomes/génétique , Tumeurs de l'intestin/génétique , Intestin grêle , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Transformation cellulaire néoplasique/anatomopathologie , Femelle , Régulation de l'expression des gènes tumoraux/génétique , Marqueurs génétiques/génétique , Humains , Tumeurs de l'intestin/anatomopathologie , Intestin grêle/anatomopathologie , Mâle , Adulte d'âge moyen , Stadification tumoraleRÉSUMÉ
This article reviews the available data on prostate cancer in Japan compared with that in the United States, with emphasis on epidemiologic, pathologic, and molecular aspects. Previous studies have demonstrated ethnic/racial differences in the incidence of prostate cancer between the two countries. Recent investigations indicate that different genetic alterations or polymorphisms are related to carcinogenesis in the prostate. Comparative geographic-pathologic autopsy studies suggest that different promoting factors including genetic, epigenetic, and environmental influences may be responsible for ethnic variations in the postinduction progression of prostate cancer.
RÉSUMÉ
A 59-year-old woman with leukorrhea. Aspiration smears were obtained from the uterine cavity. The dominant cellular components were fibrogenic sarcomatous cells, which had ill-defined lacy cytoplasm and a single nucleus with finely granular chromatin. There were occasional naked giant cells, and intracytoplasmic eosinophilic granules. Another infrequent cellular component was adenocarcinoma cells. Histopathologically, adenocarcinoma and spindle cell sarcoma were equivalently identified. Twenty-two cases of homologous carcinosarcoma of the uterine corpus were reviewed cytologically in Japan. Cytodiagnosis before treatment was positive for malignancy of carcinosarcoma in 28.6%. Characteristic cytological findings of this case were the presence of flat sheets of atypical cells with broad cytoplasm. These findings suggest epithelial features. However, the finely granular chromatin pattern and smooth nuclear membrane indicate sarcomatous cells.
Sujet(s)
Adénocarcinome/anatomopathologie , Carcinosarcome/anatomopathologie , Tumeurs primitives multiples , Tumeurs de l'utérus/anatomopathologie , Femelle , Humains , Adulte d'âge moyenRÉSUMÉ
Prostate cancers are resistant to many anticancer agents at the time of presentation. P-glycoprotein (P-gp) is believed to mediate multidrug resistance phenotype. To elucidate the possible role of P-gp in such an intrinsic drug resistance of prostate cancers, its expression was examined immunohisochemically using two P-gp isoform-specific monoclonal antibodies (mAbs) with the paraffin embedded prostate samples derived from five nonmalignant and 30 untreated prostate cancer patients. In all of five normal prostate tissues, P-gp was consistently detected with both mAbs in the epithelial cells, especially at their apical site, and the level of expression was higher in the inner zone than in outer zone. On the other hand, tumor cells expressed P-gp heterogeneously in distribution and intensity; in 25 of 30 malignant cases P-gp expression was clearly demonstrated, whereas its expression was only faintly detected in other cases. However, the staining intensities for P-gp in prostate cancer cells were generally lower than in normal prostate epithelial cells. Thus, not only normal prostate epithelial cells but prostate cancer cells express at least MDR1 P-gp isoform. These results suggest that P-gp expression might play some role in intrinsic drug resistance of prostate cancer cells to many cytotoxic drugs as well as in relative resistance of the inner zone cells to the prostate carcinogenesis.
Sujet(s)
Glycoprotéine P/analyse , Anticorps monoclonaux/immunologie , Prostate/composition chimique , Tumeurs de la prostate/composition chimique , Glycoprotéine P/immunologie , Sujet âgé , Sujet âgé de 80 ans ou plus , Humains , Immunohistochimie , Mâle , Isoformes de protéines/analyseRÉSUMÉ
OBJECTIVE: This study was performed to examine the expressions of Ki-67 antigen, bcl-2 and p53 oncoprotein and to assess their capacity to predict the short-term response to the initial endocrine treatment and disease progression in prostate cancer. METHODS: Formalin-fixed and paraffin-embedded tumor tissues from a total of 73 patients with untreated prostate cancers were collected by transrectal ultrasound-guided biopsy. All patients with stage C or D prostate cancers had received continuous endocrine treatment. Ki-67 antigen, p53 and bcl-2 oncoprotein were detected by immunohistochemical methods. RESULTS: Short-term response to initial endocrine therapy judged at 3 months showed a significant correlation with Ki-67 labeling index (LI) and bcl-2 expression. Multivariate analysis showed that only a high Ki-67 LI was an independent potential predictor of prostate-specific antigen failure or the appearance of new metastasis. CONCLUSIONS: The findings suggested that the Ki-67 LI was the most useful parameter to predict disease progression after the initial endocrine treatment. Additional studies must be performed to evaluate the prognostic significance of both cell proliferation and apoptosis in detail.
Sujet(s)
Antigène KI-67/biosynthèse , Tumeurs de la prostate/métabolisme , Tumeurs de la prostate/thérapie , Sujet âgé , Sujet âgé de 80 ans ou plus , Antagonistes des androgènes/usage thérapeutique , Évolution de la maladie , Humains , Antigène KI-67/analyse , Mâle , Adulte d'âge moyen , Stadification tumorale , Orchidectomie , Valeur prédictive des tests , Pronostic , Tumeurs de la prostate/composition chimique , Tumeurs de la prostate/anatomopathologie , Protéines proto-oncogènes c-bcl-2/analyse , Protéines proto-oncogènes c-bcl-2/biosynthèse , Protéine p53 suppresseur de tumeur/analyse , Protéine p53 suppresseur de tumeur/biosynthèseRÉSUMÉ
Epigenetic mechanisms including DNA methylation and histone deacetylation are thought to play important roles in gene transcriptional inactivation. Heterogenous expression of androgen receptor (AR), which appears to be related to variable responses to endocrine therapy in prostate cancer (PCa) may also be due to epigenetic factors. The methylation status of the 5' CpG island of the AR in 3 prostate cancer cell lines and 10 primary and 14 hormone-refractory PCa samples was determined using the bisulfite PCR methods. In DU145, CpG-rich regions of the AR were hypermethylated. By an immunohistochemical analysis, only one PCa sample had no AR expression, the others being heterogenous. Bisulfite sequencing and methylation-specific PCR analysis showed aberrant methylation of AR 5'-regulatory region in 20% of 10 primary and 28% of 14 hormone-refractory PCa samples. To clarify the effect of epigenetic regulation on AR expression, we treated three prostate cancer cell lines with a demethylating agent, 5-aza-2'-deoxycytidine (azaC), and a histone deacetylase inhibitor, Trichostatin A (TSA). In DU145, re-expression of AR mRNA was detected after treatment with azaC and/or TSA. Our results suggest that epigenetic regulations including CpG methylation and histone acetylation may play important roles in the regulation of the AR.
Sujet(s)
Azacitidine/analogues et dérivés , Régulation de l'expression des gènes tumoraux , Régions promotrices (génétique) , Tumeurs de la prostate/génétique , Récepteurs aux androgènes/génétique , Antimétabolites antinéoplasiques/toxicité , Azacitidine/toxicité , Séquence nucléotidique , Sites de fixation , Protéine de liaison à l'élément de réponse à l'AMP cyclique/métabolisme , Méthylation de l'ADN , Décitabine , Dinucléoside phosphates/métabolisme , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques , Inhibiteurs de désacétylase d'histone , Humains , Acides hydroxamiques/toxicité , Mâle , Réaction de polymérisation en chaîne , Tumeurs de la prostate/anatomopathologie , Cellules cancéreuses en cultureRÉSUMÉ
An autopsy case of a malignant pericardial mesothelioma in a 27-year-old man with no history of exposure to asbestos is reported. He was admitted for heart failure due to pericardial effusion of unknown origin and surgically drained, but later died. The diagnosis of a malignant pericardial mesothelioma was made on the basis of histologic, immunohistochemical and ultrastructural findings. The tumor was located on the pericardium, but autopsy revealed that it had spread extensively in the mediastinum and the lungs. Microscopically, the tumor cells were epithelial like and contained histochemically demonstrable glycogen and hyaluronic acid. Immunohistochemical studies of the tumor demonstrated positive immunoreactivity for cytokeratin 19, muscle actin HHF35, epithelial membrane antigen, CA125, p53 and p21WAF1/CIP1 whereas the tumor was negative for cytokeratins 10 and 17, carcinoembryonic antigen, vimentin, epithelial antigen BerEP4, S-100, c-erbB2 and bcl-2. A high MIB-1 labeling index was noted. Under the electron microscope the tumor cells exhibited long, thin villi. The operation and autopsy findings thus revealed this to be a very rare case of malignant pericardial mesothelioma in a young man.
Sujet(s)
Tumeurs du coeur/anatomopathologie , Tumeurs du poumon/secondaire , Tumeurs du médiastin/secondaire , Mésothéliome/secondaire , Péricarde/anatomopathologie , Adulte , Marqueurs biologiques tumoraux/analyse , Desmosomes/ultrastructure , Issue fatale , Glycogène/ultrastructure , Tumeurs du coeur/composition chimique , Tumeurs du coeur/imagerie diagnostique , Humains , Techniques immunoenzymatiques , Tumeurs du poumon/composition chimique , Imagerie par résonance magnétique , Mâle , Tumeurs du médiastin/composition chimique , Mésothéliome/composition chimique , Mésothéliome/imagerie diagnostique , Microscopie électronique , Microvillosités/ultrastructure , Épanchement péricardique/imagerie diagnostique , Épanchement péricardique/étiologie , Épanchement péricardique/anatomopathologie , Péricarde/composition chimique , Péricarde/imagerie diagnostique , Radiographie thoracique , Jonctions serrées/ultrastructureRÉSUMÉ
While pancreaticobiliary maljunctions (PBM) are clearly associated with biliary tract tumor development, little is known about their molecular mechanisms. This study was conducted to assess the contributions of microsatellite instability (MSI), mutations of transforming growth factor type II receptor (TGF-beta RII) and insulin-like growth factor type II receptor (IGF RII) genes and loss of heterozygosity (LOH) of hMSH2 and hMLH1 in 23 biliary tract tumors using PCR methods. MSI was detected by 13 markers in 16/23 samples (69.6%). TGF-beta RII mutations were detected in eight of these (50%), and of the IGF IIR gene in two (12.5%). LOH was detected in 4/16 (25%) at the hMSH2 locus, and 2/16 (12.5%) at the hMLH1 locus. No TGF-beta RII mutations or LOH of hMSH2 and hMLH1 were detected in MSI-negative samples. These findings suggest that MSI plays an important role in carcinogenesis of the biliary tract epithelium with PBM cases.
Sujet(s)
Ampoule hépatopancréatique/malformations , Conduits biliaires/malformations , Tumeurs des voies biliaires/génétique , Protéines de liaison à l'ADN , Répétitions microsatellites , Protéines tumorales/génétique , Protéines proto-oncogènes/génétique , Récepteurs TGF-bêta/génétique , Protéines adaptatrices de la transduction du signal , Sujet âgé , Allèles , Protéines de transport , Malformations/génétique , Analyse de mutations d'ADN , ADN tumoral/génétique , Femelle , Fréquence d'allèle , Prédisposition génétique à une maladie , Humains , Perte d'hétérozygotie , Mâle , Adulte d'âge moyen , Protéine-1 homologue de MutL , Protéine-2 homologue de MutS , Protéines nucléaires , Réaction de polymérisation en chaîne , Protein-Serine-Threonine Kinases , Récepteur de type II du facteur de croissance transformant bêtaRÉSUMÉ
The c-met proto-oncogene encoding the receptor for the hepatocyte growth factor is expressed in several cancers. In the present study, c-met protein (c-Met) was detected in eight of 22 (36%) cases of prostatic intraepithelial neoplasia (PIN), five of 15 (33%) latent and 17 of 21 (81%) clinical prostate cancers, including seven metastatic lesions, using an immunohistochemical method. All seven (100%) metastatic lesions investigated demonstrated strong staining, and a correlation between c-Met expression and histology was observed. These results suggest a significant relationship between c-Met expression and progression of prostate neoplasms, including latent cancers.
Sujet(s)
Adénocarcinome/métabolisme , Tumeur intraépithéliale prostate/métabolisme , Tumeurs de la prostate/métabolisme , Protéines proto-oncogènes c-met/biosynthèse , Adénocarcinome/anatomopathologie , Adénocarcinome/secondaire , Sujet âgé , Évolution de la maladie , Humains , Immunohistochimie , Mâle , Valeur prédictive des tests , Tumeur intraépithéliale prostate/anatomopathologie , Tumeurs de la prostate/anatomopathologie , Tumeurs de la prostate/secondaire , Proto-oncogène MasRÉSUMÉ
The potential involvement of N-acetyltransferase 1 (NAT1) genetic polymorphisms in prostate cancer (PCa) patients was analyzed in 101 patients with PCa and 97 controls with no incidental malignancy. Identification of NAT1*10, the variant allele associated with the rapid acetylator phenotype was by allele-specific polymerase chain reaction (PCR). When the NAT1*10 heterozygote and other genotypes without NAT1*10 allele were considered as low risk genotypes, NAT1*10/NAT1*10 had a significantly higher risk of PCa (OR = 2.4, 95% CI; 1.0-5.6). If our preliminary results can be confirmed in a larger population, it may be a useful marker for PCa risk.
Sujet(s)
Arylamine N-acetyltransferase/génétique , Marqueurs biologiques tumoraux/génétique , Isoenzymes/génétique , Polymorphisme génétique , Tumeurs de la prostate/enzymologie , Tumeurs de la prostate/génétique , Allèles , Études cas-témoins , Génotype , Hétérozygote , Humains , Mâle , Réaction de polymérisation en chaîne , Risque , Facteurs de risqueRÉSUMÉ
A cell line, designated OSrb/N-M, was established from the second primary osteosarcoma that developed in a 17-year-old Japanese female patient who had suffered from bilateral retinoblastoma at infancy. The OSrb/N-M cells grew as an adherent monolayer and retained some osteogenic biochemical phenotypes. In cytogenetic analyses, this cell line revealed many structural and numerical abnormalities, however, the bands q14 of both chromosomes 13 appeared to be normal, whereas the constitutional cells displayed normal female karyotypes. Immunoblot studies using monoclonal antibodies specific to RB protein demonstrated that the tumor cells did not express RB protein, suggesting that the OSrb/N-M cells might suffer from a loss-of-function mutation at this gene locus. Thus, this cell line is useful to study the molecular mechanism for the tumorigenesis of osteosarcoma with regard to an association with retinoblastoma.
Sujet(s)
Ostéosarcome , Tumeurs de la rétine , Rétinoblastome , Adolescent , Phosphatase alcaline/métabolisme , Techniques de culture cellulaire/méthodes , Femelle , Humains , Nourrisson , Caryotypage , Ostéosarcome/enzymologie , Ostéosarcome/génétique , Ostéosarcome/anatomopathologie , Ostéosarcome/ultrastructure , Tumeurs de la rétine/enzymologie , Tumeurs de la rétine/génétique , Tumeurs de la rétine/anatomopathologie , Tumeurs de la rétine/ultrastructure , Rétinoblastome/enzymologie , Rétinoblastome/génétique , Rétinoblastome/anatomopathologie , Rétinoblastome/ultrastructure , Protéine du rétinoblastome/biosynthèse , Protéine du rétinoblastome/génétique , Cellules cancéreuses en cultureRÉSUMÉ
We report two cases of intraadrenal thyroid gland tissue, both found by abdominal computed tomography (CT) scan and ultrasound echography. Histologically, the lesions were composed of mature thyroid follicles, varying in size, and some with cystic dilatation. Immunohistochemical staining for thyroglobulin confirmed their thyroid follicular nature. In neither case was there any evidence of thyroid gland cancer or teratomatous elements. Clinical examinations, including CT, ultrasound echography, and scintscanning did not show any tumorous lesions in the thyroid gland or elsewhere. The cause of ectopic thyroid in the adrenal gland is not known. It seems difficult to explain these ectopic lesions on the basis of developmental error because their location is distant from the path of embryological descent of the thyroid. The most important practical consideration is that they must be distinguished from metastatic deposits from a clinical point of view.
Sujet(s)
Maladies des surrénales/diagnostic , Choristome/diagnostic , Glande thyroide , Maladies des surrénales/anatomopathologie , Choristome/anatomopathologie , Femelle , Humains , Mâle , Adulte d'âge moyen , TomodensitométrieRÉSUMÉ
Vitamin D receptor gene (VDR) polymorphisms have been reported to be related to prostate cancer risk in the USA. We analyzed the distribution of TaqI RFLP and poly(A) of VDR in 100 prostate cancer patients and 202 urological controls. Among the control, 79.2% were homozygous (TT) for the absence of a TaqI RFLP, while 17.8% were heterozygous (Tt) and 3.0% homozygous (tt) for its presence. The distribution was almost the same in the cancer group; 80% were homozygous TT, 18% heterozygous Tt, and 2.0% homozygous tt. Polymorphism of poly(A) sizes was categorized as a long allele (> or = 18 As) and a short allele (< 18 As). The distribution did not vary between the cancer and control groups; 80, 79.2% were LL, 18, 17.8% LS and 2.0, 3.0% SS, respectively. These results showed no significant association of two VDR polymorphisms with prostate cancer risk, however a different distribution of VDR polymorphisms between Japanese and non-Japanese men.
Sujet(s)
Tumeurs de la prostate/épidémiologie , Tumeurs de la prostate/génétique , Récepteur calcitriol/génétique , Sujet âgé , Études cas-témoins , Humains , Japon , Mâle , Projets pilotes , Réaction de polymérisation en chaîne , Polymorphisme génétique , Facteurs de risqueRÉSUMÉ
BACKGROUND: The p53 mutation spectrum of prostate cancers developing in Japan indicates a role for environmental factors. This suggests there might be differences in susceptibility due to genetic polymorphisms in metabolic activation enzyme genes. We analyzed genetic polymorphisms of the xenobiotic-metabolizing enzymes, CYP1A1 and GSTM1. METHOD: Genotyping of CYP1A1 and GSTM1 was investigated by using allele-specific PCR in 115 prostate cancer (PCa) patients and 204 control patients. RESULTS: The CYP1A1 Val/Val genotype significantly increased the risk for PCa (OR = 2.6; 95% CI = 1.11-6.25) and the Ile/Val genotype showed a similar tendency (OR = 1.4; CI = 0.86-2.29). Individuals with the GSTM1 (0/0) genotype demonstrated a slightly increased risk (OR = 1.3; CI = 0.82-2.04). The combination of the CYP1A1 Val allele and GSTM1 (0/0) genotype was associated with a higher risk (OR = 2.3; CI = 1.18-4.48) than the CYP1A1 Val allele alone. When cases were analyzed by age at initial diagnosis, the relative risks with both the CYP1A1 Val allele and the GSTM1 (0/0) genotype were higher in the young group than in the old group (CYP1A1; OR = 1.7, CI = 0.89-3.17: GSTM1; OR = 1.6, CI = 0.84-2.99). The frequency of the GSTM1 (0/0) genotype was also higher in patients with advanced stage disease. In stage D, the OR was 1.7 with a CI of 0.93-3.17 and in stages A and B, the OR was 0.8 with a CI of 0.40-1.62. CONCLUSIONS: These results suggest that CYP1A1 and GSTM1 polymorphisms are linked to a propensity for PCa development.
Sujet(s)
Cytochrome P-450 CYP1A1/génétique , Glutathione transferase/génétique , Tumeurs de la prostate/enzymologie , Sujet âgé , Sujet âgé de 80 ans ou plus , Génotype , Humains , Mâle , Polymorphisme génétique , Tumeurs de la prostate/génétique , Facteurs de risqueRÉSUMÉ
A series of 25 primary prostate cancers in Japanese were screened for loss of heterozygosity and microsatellite instability using twelve microsatellite markers containing APC, DCC, TP53, BRCA1, and BRCA2. Frequent loss of heterozygosity was observed for D8S201 (48%), LPL (48%), and DCC (26%). In contrast, the incidence did not exceed 15% at BRCA1 and BRCA2 loci. Microsatellite instability was observed in 28% of stage B, C, and D cancers. These data suggest that microsatellite instability and loss of unidentified genes on chromosome 8p may be involved in carcinogenesis of the prostate; however, BRCA1 and BRCA2 may not be largely involved in the development of prostate cancer in the Japanese population.
Sujet(s)
Allèles , ADN tumoral/génétique , Perte d'hétérozygotie , Répétitions microsatellites , Tumeurs de la prostate/génétique , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Chromosomes humains de la paire 17 , Chromosomes humains de la paire 8 , Gènes suppresseurs de tumeur , Marqueurs génétiques , Humains , Mâle , Adulte d'âge moyen , Réaction de polymérisation en chaîneRÉSUMÉ
Point mutations of the ras gene family are thought to be involved in the development of a variety of human tumors. However, it remains unknown whether the ras gene might play a key role in prostate carcinogenesis. We therefore analysed Ki-,N- and H-ras gene mutations in a series of 81 Japanese prostate cancers using PCR-SSCP analysis and Mutant-Allele-Specific Amplification (MASA) method. Mutated as genes were detected in 20 of the 81 samples (24%); three of 22 latent, one of five stage B, four of 14 stage C and 12 of 40 stage D cancers. Of the twenty as gene mutations, 13 were in Ki-ras (codon 12), five in H-ras codon 61 and two H-ras codon 13. The observed frequency of ras gene mutations was higher than that reported in the literature for some non-Japanese prostate cancers, suggesting the possibility of genetic differences between populations.