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Biomedical subjects

Tetsuro Kato

Publications and source records attributed to Tetsuro Kato.

At least 19 recordsLinked to original sources

Association of BCL10 germ line polymorphisms on chromosome 1p with advanced stage testicular germ cell tumor patients.

The association between four BCL10 single nucleotide polymorphisms at codons 5, 8, 162, and intron 1 and the susceptibility or progression for germ cell tumors (GCTs) was investigated in 73 testicular GCT patients and 72 controls. GCT patients with metastatic disease were more likely to have a variant type allele of the polymorphisms at codon 5 (age-adjusted odds ratio (aOR)=6.25; 95% CI=1.09-35.83; P=0.040) and codon 8 (aOR=4.63; 95% CI=1.35-15.93; P=0.015) than those with the localized disease. Therefore, BCL10 polymorphisms at codons 5 and 8 may play a role in the progression to advanced stage GCTs.

Adaptor Proteins, Signal Transducing↗

CYP3A5 gene polymorphism and risk of prostate cancer in a Japanese population.

The CYP3A5 gene (CYP3A5) encodes the cytochrome P450 3A5, which catalyzes the 6beta-hydroxylation of testosterone. We explored association between the CYP3A5 A6986G polymorphism and a risk of prostate cancer in 260 prostate cancer patients, 199 BPH patients and 212 male controls. The CYP3A5 gene polymorphism did not influence significantly a risk of developing of prostate cancer in general. However, compared with males with the GG genotype, those with the AA genotype had a 0.23-fold decreased risk of developing low-grade prostate cancer (P=0.023), and a 0.31-fold decreased risk of developing localized (stages A-C) prostate cancer (P=0.044). The CYP3A5 A6986G polymorphism may be specifically associated with a decreased risk of low-grade or early stage prostate cancer.

Aged↗

A long-term survival case of small cell lung cancer in an HIV-infected patient.

We report a case of small cell lung cancer in a patient with human immunodeficiency virus (HIV) infection. The patient was a 51-year-old man diagnosed 8 years previously as seropositive for HIV, who was admitted to our hospital for re-evaluation of antiretroviral medications due to multidrug resistance. Chest radiograph revealed an abnormal hilar shadow subsequently confirmed to be small cell lung cancer. He received chemotherapy concurrently with highly active antiretroviral therapy (HAART), and lived for 14 months after the diagnosis. The prognosis of lung cancer in HIV-seropositive patients is very poor, and adverse effects of chemotherapy occur more frequently than in other patients. However, the simultaneous antiretroviral agents and combination chemotherapy was successful. Such treatment may be effective despite an otherwise poor prognosis, including HIV infection.

Alkynes↗

Association of a genetic polymorphism of the E-cadherin gene with prostate cancer in a Japanese population.

The E-cadherin gene has been identified as having a physiological role in cellular attachment, and is hypothesized to participate in carcinogenesis. A polymorphism (an A to C substitution) in the 5'-untranslated region has a direct effect on E-cadherin gene transcriptional regulation. We explored the association between E-cadherin gene polymorphism and the risk of prostate cancer in a Japanese population. The subjects consisted of 236 patients with prostate cancer, 209 benign prostatic hyperplasia (BPH) patients and 139 male controls. A marginally significant difference was found between prostate cancer patients and male controls (P = 0.053). No significant difference was observed between prostate cancer and BPH patients. When patients with prostate cancer were divided into two groups, stage A+B and stage C+D, a significant difference was observed between progressive cancer patients (stage C+D) and male controls (odds ratio = 1.93, P = 0.016). It is possible that the presence of one A allele resulted in an increased risk of cancer progression.

Aged↗

Activation of natural killer T cells by alpha-galactosylceramide mediates clearance of bacteria in murine urinary tract infection.

PURPOSE: alpha-Galactosylceramide (alpha-GalCer), which is a specific ligand for CD1d restricted variable-alpha14chain natural killer T cells, has an important role in host defense against a range of microbial infections. We examined whether alpha-GalCer mediates bacterial clearance in a murine urinary tract infection (UTI) model. MATERIALS AND METHODS: The murine UTI model was established by intravesical inoculation of Escherichia coli, Pseudomonas aeruginosa or methicillin resistant Staphylococcus aureus, followed by clamping the distal end of the urethra of C57BL/6 female mice for 4 hours. The antibacterial effect of alpha-GalCer was assessed by comparing the number of cfu/gm kidney tissue 4 days after bacterial inoculation. The prophylactic effect of alpha-GalCer was examined by administrating 3 doses of intraperitoneal alpha-GalCer on alternate days 24 hours before E. coli inoculation. The therapeutic effect of alpha-GalCer was tested by the administration of 2 doses of intraperitoneal alpha-GalCer after bacterial inoculation. To assess cytokine induction by alpha-GalCer serum levels of interleukin-12, interferon-gamma and tumor necrosis factor-alpha were measured by cytometric bead array assay. RESULTS: When administered before bacterial inoculation, alpha-GalCer showed a strong prophylactic antibacterial effect. alpha-GalCer also showed a marked antibacterial effect on preestablished mice UTI caused by E. coli, P. aeruginosa and methicillin resistant S. aureus. alpha-GalCer induced a significantly higher level of interleukin-12, interferon-gamma and tumor necrosis factor-alpha compared with control glycolipids. CONCLUSIONS: These findings suggest a significant role for alpha-GalCer in regulating antibacterial functions by activating natural killer T cells in the murine UTI model.

Animals↗

Renal cell and transitional cell carcinoma in a Japanese population undergoing maintenance dialysis.

PURPOSE: We verified differences in the incidence, clinical characteristics and outcomes between patients on chronic dialysis for end stage renal disease with renal cell carcinoma (RCC) and those with transitional cell carcinoma (TCC). MATERIALS AND METHODS: Data regarding RCC and TCC were reviewed in the medical records of 6,201 patients with end stage renal disease who underwent chronic dialysis between January 1990 and June 2003 in our 38 affiliated dialysis centers, and data were compared with those reported in Australia and New Zealand. RESULTS: Among the patients RCC developed in 38 (0.61%) and TCC developed in 16 (0.26%) during maintenance dialysis. The primary renal disease was chronic glomerulonephritis in patients with RCC (68.4%) and diabetic nephropathy in patients with TCC (43.8%, p = 0.002). Mean patient age at initiation of dialysis was 45 years for those with RCC and 63 for those with TCC (p < 0.001). Mean interval from dialysis induction to tumor diagnosis was 143 months for patients with RCC and 54 months for patients with TCC (p < 0.001). Of 38 RCCs 23 (60.5%) were incidentally detected by regular abdominal imaging examinations while painless gross hematuria was the cardinal symptom in 13 (81.2%) of 16 TCCs. Overall and cancer specific survivals after tumor diagnosis were significantly superior in patients with RCC compared to those with TCC (p = 0.0001 and p = 0.0003, respectively), and the cancer specific 5-year survival was 88.9% for RCC and 29.5% for TCC. In both cancers tumor stage significantly increased the risk of cancer specific death. Compared with patients from Australia and New Zealand, the incidence of RCC was higher and that of TCC was lower in our patients (p <0.001). CONCLUSIONS: In the Japanese population on dialysis RCC is more common than TCC. Since long-term dialysis is a risk factor for RCC, regular imaging examinations may have contributed to the favorable outcome of our patients on dialysis with RCC. In contrast, the unfavorable outcome of TCC suggests the need for effective diagnostic measures for early detection of TCC in patients on dialysis.

Adolescent↗

Successful renal transplantation in the right iliac fossa 2 years after serious deep venous thrombosis in a patient with systemic lupus erythematosus.

Deep venous thrombosis (DVT) possibly occurs in the perioperative period, and induces serious complications such as a pulmonary embolism. On the other hand, allograft renal vein thrombosis leads to a high incidence of graft loss. We experienced a case in which a serious DVT occurred prior to renal transplantation; however, a successful renal transplantation in the right iliac fossa was performed after 2 years of anticoagulant therapy. It is suggested that the external iliac vein even after suffering from DVT can be anastomosed to an allograft vein successfully, when enough blood fl ow or a lower venous pressure is confirmed. However, one should be aware of the risk factors and the adequate management of thrombosis in renal transplantation because of the serious complications of DVT and the poor prognosis of allograft vein thrombosis.

Adult↗

A retrospective study of the treatment of locally advanced prostate cancer by six institutions in eastern and north-eastern Japan.

OBJECTIVE: To investigate patients with locally advanced prostate cancer treated at six academic institutions in eastern and north-eastern Japan from 1988 to 2000, to facilitate the establishment of Japanese guidelines for the diagnosis and treatment of locally advanced prostate cancer. PATIENTS AND METHODS: The study included 391 eligible patients with locally advanced prostate cancer who were treated by radical prostatectomy (RP), radiotherapy and/or primary hormone therapy. Disease-specific survival rates for these patients were assessed in relation to their clinicopathological characteristics and the types of treatment they received. The Mann-Whitney U-test, Kruskal-Wallis, chi-square and log-rank test were used for statistical analysis, as appropriate. RESULTS: In all, 128 patient with lower prostate-specific antigen levels (P = 0.023) and/or better performance status (P = 0.001) had RP. Neoadjuvant hormone therapy before RP was the treatment in 68 (53%) of these 128 patients; 66 (52%) received immediate adjuvant hormone therapy. Of 87 patients treated with radiotherapy, 75 (86%) had external beam radiotherapy (EBRT) as the primary treatment with no brachytherapy, and 12 (14%) had brachytherapy as the primary method. Neoadjuvant hormone therapy was given to 56 of the 87 patients (64%); 48 (55%) received immediate adjuvant hormone therapy. Of the 176 patients treated with primary hormone therapy alone, combined androgen blockade and surgical or medical castration was the treatment in 76 (43%) and 85 (48%), respectively. Disease-specific survival rates at 5 years for patients treated with RP, EBRT and primary hormone therapy were 90%, 98%, and 89%, respectively. CONCLUSION: The treatments provided by the participating institutions did not differ significantly from those set out in European and American guidelines, and short-term disease-specific survival rates for each treatment did not differ significantly from those of historical controls. Further investigation may facilitate the establishment of Japanese guidelines for the diagnosis and treatment of locally advanced prostate cancer.

Aged↗

[A case of leptospirosis caused by Leptospira borgpetersenii serovar sejroe infected in Bali Island, Indonesia].

We report a patient with leptospirosis caused by Leptospira borgpetersenii serovar Sejroe infection on Bali Island, Indonesia. This 33-year-old Japanese man had stayed at a resort hotel on the island from July 8 to July 13 2004. At the hotel, he swam in the pool, walked barefoot, and lied down in the grass. He developed a high fever and headache 7 days after completing his trip, and was admitted to our hospital on July 23. On admission he showed conjunctival suffusion and complained of myalgias. Laboratory findings included granulocytosis and elevated CRP. Plasmodium spp. were not found in blood smears, and no pathogenic bacteria were isolated from blood or fecal cultures. We diagnosed the patient as leptospirosis upon detection of slender coiled organisms with characteristic morphology by darkfield examination of blood sample. Minocycline 100 mg i.v.b.i.d. showed excellent efficacy. A microscopic agglutination test (MAT) during the convalescent stage demonstrated a significant increase in antibodies against L. borgpetersenii serovar Sejroe, confirming the diagnosis of leptospirosis. Despite occurrence of a pandemic of leptospirosis in certain Southeast Asian countries including Indonesia, information concerning pandemic disease is limited. In addition serovars of "imported" cases representing infection in pandemic areas differ widely from those in domestic cases. Adequate laboratory support therefore is crucial for accurate diagnosis of leptospirosis.

Adult↗

CA repeat polymorphism in the insulin-like growth factor-I gene is associated with increased risk of prostate cancer and benign prostatic hyperplasia.

Insulin-like growth factor-I (IGF-I) plays an important role in prostate growth, hyperplasia, and carcinogenesis. Circulating IGF-I levels may be modulated by a genetic cytosine-adenine (CA) repeat polymorphism in the promoter region of IGF-I. The association of the polymorphism with the risk of prostate cancer and benign prostatic hyperplasia (BPH) was explored in 303 patients with prostate cancer, 219 patients with BPH and 262 controls. The number of CA repeats ranged from 15 to 22 in case and control subjects. The 19-CA-repeat allele (19-allele) was more frequently observed in both the prostate cancer and BPH patients compared with the controls (prostate cancer versus control: P<0.001; BPH versus control: P=0.001). Compared with non-carriers of the 19-allele, men homo-zygous for the 19-allele had a significantly increased risk of prostate cancer [age-adjusted odds ratio (aOR) = 3.36, 95% confidence intervals (CI) = 1.30-8.67, P=0.012] or BPH (aOR = 3.53, 95% CI = 1.32-9.46, P=0.012), and those heterozygous for the 19-allele also had an intermediate increased risk of prostate cancer (aOR = 1.78, 95% CI = 1.25-2.53, P=0.001) or BPH (aOR = 1.66, 95% CI = 1.14-2.43, P=0.009). A gene dosage effect for the aORs was found with an increasing number for the 19-allele (P<0.001 in prostate cancer and P=0.001 in BPH). No significant association was found between the presence of the 19-allele and the tumor stage and grade at the time of diagnosis. In conclusion, the 19-allele of IGF-I appears to increase the risk of prostate cancer and BPH with a gene dosage effect in the Japanese population.

Alleles↗

[Two cases of urothelial cancer responsive to high-dose-intensity methotrexate vinblastine doxorubicin and cisplatin (M-VAC) therapy].

We report two cases of metastatic urothelial cancer treated with high-dose-intensity (HD) methotrexate vinblastine, doxorubicin and cisplatin (MVAC). After HD-MVAC, the size of primary and lymph node tumors decreased by 57-67% as compared with the standard M-VAC therapy. By shortening the dose interval, HD-MVAC may increase the anti-tumor effect without increasing side effects.

Aged↗

Association of lipoprotein lipase gene polymorphism with risk of prostate cancer in a Japanese population.

A high fat intake has been associated with prostate cancer risk, and gene polymorphisms of lipoprotein lipase (LPL) play an important role in plasma lipoprotein metabolism. We herein analyzed the association of LPL gene polymorphisms with the risk of prostate cancer in a Japanese population. Three single nucleotide polymorphisms (SNPs) of LPL designated as Ser447stop, HindIII and PvuII were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method in 273 prostate cancer patients, 205 benign prostatic hyperplasia (BPH) patients and 230 male controls. The men with the CG + GG genotypes of the Ser447stop polymorphism had an increased risk of prostate cancer compared to those with the CC genotype [age-adjusted odds ratio (aOR) = 1.625; 95% CI = 1.068-2.471; p = 0.023]. Furthermore, the increased risk associated with the CG + GG genotypes was more strongly observed in patients with high-grade cancers (aOR = 2.843; 95% CI = 1.252-6.458; p = 0.039) or metastatic diseases (aOR = 2.300; 95% CI = 1.042-5.074; p = 0.013), whereas the risk was not significant in those with low- to intermediate-grade cancers or nonmetastatic diseases. In the HindIII and PvuII polymorphisms, there was no significant difference between the prostate cancer patients and the controls, and no significant results as for tumor grade and stage. None of the 3 polymorphisms showed any association with the risk of BPH. Our results suggest that the LPL Ser447stop polymorphism is a common genetic modifier for the development of prostate cancer, particularly that of high-grade and/or high-stage, in a Japanese population.

Aged↗

Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients.

BACKGROUND: A body-weight-based dose of tacrolimus often results in marked individual diversity of blood drug concentration. Tacrolimus is a substrate for cytochrome P450 (CYP) 3A5 and p-glycoprotein encoded by CYP3A5 and MDR1 (ABCB1), respectively, having multiple single nucleotide polymorphisms. In this study, we genotyped CYP3A5 A6986G, MDR1 G2677(A/T), and C3435T polymorphisms and investigated the association between these polymorphisms and the pharmacokinetics of tacrolimus in renal transplant recipients. METHODS: Thirty consecutive recipients were enrolled in this study. The pharmacokinetics of tacrolimus was analyzed on day 28 after transplant, when the daily dose was adjusted to the target trough level of 10-15 ng/mL. The polymerase chain reaction-restriction fragment length polymorphism and direct sequence method were used for genotyping the CYP3A5 and MDR1 polymorphisms, respectively. RESULTS: The single tacrolimus dose per body weight was significantly higher in CYP3A5 *1 carriers than CYP3A5 *3/*3 carriers (0.143+/-0.050 vs. 0.078+/-0.031 mg/kg, P<0.001). The dose-adjusted trough level and the area under the concentration-time curve (AUC0-12) were significantly lower in CYP3A5 *1 carriers than CYP3A5 *3/*3 carriers (0.040+/-0.014 vs. 0.057+/-0.024 ng/mL/mg/kg, P=0.015 and 0.583+/-0.162 vs. 0.899+/-0.319 ng.hr/mL/mg/kg, P=0.004), respectively. The MDR1 polymorphism was not associated with any pharmacokinetic parameters. CONCLUSIONS: Kidney transplant recipients with the CYP3A5 *1 allele required a higher daily tacrolimus dose compared with those with the CYP3A5 *3/*3 genotype to maintain both the target trough level and AUC0-12, suggesting that this polymorphism is useful for determining the appropriate dose of tacrolimus.

Adult↗

Functional correlation of trophinin expression with the malignancy of testicular germ cell tumor.

Trophinin is a membrane protein that is potentially involved in human embryo implantation by mediating homophillic cell adhesion between trophoblastic cells and endometrial cells. Trophinin expression by maternal cells may be induced by the embryo that secretes human chorionic gonadotropin (hCG). Because the process of tumor metastasis resembles that of trophoblast invasion and proliferation during embryo implantation, we hypothesized that testicular cancers that synthesize hCG express trophinin thus becoming aggressive trophoblast-like cells. We screened paraffin-embedded orchiectomy specimens of 158 patients with testicular germ cell tumor by immunohistochemistry using antitrophinin antibody. This screening identified trophinin-positive specimens with the frequencies 39 of 91 (43%) in stage I, 14 of 24 (58%) in stage II, and 41 of 43 (95%) in stage III (P < 0.001). Thus, trophinin expression positively correlates with clinical stage. Remarkably, trophinin was found in all of the cases (33 of 33) with lung metastasis. The levels of serum hCG-beta were significantly higher in the patients with trophinin-positive tumors than those with trophinin-negative tumors (P = 0.004). To determine whether trophinin promotes aggressiveness of the cell, trophinin-negative human seminona cell line JKT-1 was stably transfected with a mammalian expression vector containing trophinin cDNA. In vitro assays revealed that trophinin-expressing JKT-1-Tro cells are more invasive than JKT-1-mock cells, whereas there are no differences between JKT-1-Tro and JKT-1-mock in their proliferation activity. Upon orthotopic inoculation to athymic nude mice, JKT-1-Tro cells exhibited i.p. metastases in all of the mice (n = 5), whereas JKT-1-mock produced no metastases (n = 5). These results suggest strongly that trophinin enhances invasiveness of the cells and promotes metastasis of testicular germ cell tumor.

Animals↗

Microsatellite polymorphism of steroid hormone synthesis gene CYP11A1 is associated with advanced prostate cancer.

It is widely recognized that androgen biosynthesis and metabolism are associated with the development and progression of prostate cancer. The human CYP11A1 gene (CYP11A1) encodes the P450scc enzyme, which mediates the first step in sex steroid hormone synthesis. The gene contains a (tttta)n-5 bp tandem repeat microsatellite polymorphism located at 528 bp upstream of the translation initiation site and the CYP11A1 mRNA level may be modulated by the polymorphism. Recent studies suggested that the absence of the shortest (tttta)4 allele of the CYP11A1 polymorphism was associated with a risk of polycystic ovary syndrome and with a hyperandrogenic state in polycystic ovary syndrome patients. In our study which included 278 prostate cancer patients, 213 benign prostatic hyperplasia (BPH) patients and 299 male controls, we explored the association between the CYP11A1 polymorphism and prostate cancer on the hypothesis that the presence of the (tttta)4 allele may increase the risk of the development or progression of prostate cancer. In addition, we measured the serum levels of 6 steroid hormones or their metabolite (i.e., testosterone, free-testosterone, estrone, estradiol, dehydroepiandrosterone and androstendione) in 156 control males subjects and compared those with and without the (tttta)4 allele. The polymorphism was evaluated by PCR amplification of a 145-170 bp fragment followed by polyacrylamid gel electrophoresis. The CYP11A1 allele consisted of 4, 6, 7, 8 and 9 (tttta)-5 bp repeats. There was no significant difference in the genotype frequency as for the presence of the (tttta)4 allele between prostate cancer patients and male controls, and between prostate cancer patients and BPH patients. However, there was a significant difference in the genotype frequency in relation to the disease status. Prostate cancer patients without the (tttta)4 allele had an increased risk of metastatic disease (stage D) compared to those with the (tttta)4 allele [adjusted odds ratio (aOR)=1.76, 95% confidence interval (Cl)=1.07-2.90 and p =0.026]. Patients without the (tttta)4 allele had an increased risk of high grade prostate cancer (Gleason score 8 or more, or poorly differentiated cancer) compared to those with the (tttta)4 allele (aOR=1.79, 95% Cl=1.08-2.97 and p =0.025). No significant difference in the serum levels of 6 steroid hormones or their metabolites was found in the presence or absence of the (tttta)4 allele. Our results suggest that the CYP11A1 polymorphism may have a significant influence on the development of advanced and/or high grade prostate cancer and the absence of the CYP11A1 (tttta)4 allele, i.e., the homozygosity for the (tttta)6 or longer allele, could be a useful marker for the prediction of disease progression of prostate cancer.

Aged↗

Hand-assisted retroperitoneoscopic nephrectomy for living kidney transplantation: initial 44 cases.

OBJECTIVES: To report our technique and early results of hand-assisted retroperitoneoscopic nephrectomy (HARN) for living donor transplantation and to assess its feasibility. METHODS: HARN was effectively and safely performed on 44 donors from July 2001 to September 2003 at Akita University Medical Center. We describe our techniques and experiences with HARN and compare the early results with those of 27 cases of open donor nephrectomy at our institution. RESULTS: The mean operating time was 260 minutes (range 173 to 445), the mean estimated blood loss was 249 mL (range 15 to 967), and the mean warm ischemia time was 2.2 minutes (range 0.8 to 6.4). These parameters were similar to those of open donor nephrectomy. Intraoperative and postoperative complications occurred in 1 (2.3%) and 2 (4.6%) cases, respectively, but they were all minor. HARN was converted to open nephrectomy in 1 case (2.3%) because of uncontrollable bleeding. All HARN donors were ambulant within 2 days postoperatively and could initiate oral intake on the first postoperative day. Regarding graft function, 41 recipients (93.2%) had an immediate onset of diuresis and 3 (6.8%) had delayed renal function. The serum creatinine 7 days and 1 month postoperatively was not significantly different between the HARN group and the open nephrectomy group. CONCLUSIONS: HARN for living donors is one excellent option for donor nephrectomy because the procedure does not require intraperitoneal manipulation, thus reducing the risk of abdominal visceral injury, and also because of the minimal warm ischemia time owing to rapid extraction of the kidney with hand assistance.

Adult↗

Numeric aberrations of HER-2 and chromosome 17 detected by fluorescence in situ hybridization in urine-exfoliated cells from patients with urothelial carcinoma.

OBJECTIVES: To elucidate the clinical significance of the HER-2 gene alterations in urine-exfoliated cells detected by fluorescence in situ hybridization (FISH) in patients with urothelial transitional cell carcinoma. METHODS: The relative increase of HER-2 (RI-HER2) and gain of chromosome 17 (G-17) in urine-exfoliated cells were examined using DNA probes for HER-2 and the chromosome 17 centromere in 103 patients. In addition, FISH analysis was performed using corresponding paraffin-embedded tissue sections from 45 cases to compare the results obtained using urine-exfoliated cells and those obtained using paraffin-embedded tissue. RESULTS: RI-HER2 and G-17 was found in 23 (22.3%) and 46 (44.6%) of 103 patients, respectively. RI-HER2 was significantly more frequent in tumors with two or more recurrences (40.7% versus 15.8%, P = 0.010) and in those with carcinoma in situ (CIS) (35.4% versus 15.9%, P = 0.029). G-17 was more frequent in high-grade tumors (69.1% versus 16.7%, P = 0.032), invasive tumors (63.6% versus 14.3%, P < 0.001), and in patients with CIS (77.1% versus 29.0%, P < 0.001). The positive rate for FISH (presence of RI-HER2 and/or presence of G-17) tended to be more frequent in FISH than in cytology. A comparison of the analyses using urine-exfoliated cells and paraffin-embedded tissue showed identical results in 36 (80.0%) of 45 cases. CONCLUSIONS: Numeric alterations of the chromosome 17 centromere in urine-exfoliated cells detected by FISH may reflect the malignant potential of urothelial carcinoma. In addition, a relative increase in HER-2 was associated with the number of recurrences and the presence of CIS.

Aged↗

Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant.

PURPOSE: The glutathione peroxidase 1 gene (GPX1) and the manganese superoxide dismutase gene (MnSOD) encode the main antioxidant enzymes that detoxify endogenous reactive oxygen species involved in carcinogenesis. Polymorphisms of GPX1 and MnSOD genes, and the risk of transitional cell cancer of the bladder were tested. MATERIALS AND METHODS: Genotypes of the leucine (Leu) to proline (Pro) polymorphism at codon 198 of GPX1, the alanine (Ala) to Valine (Val) polymorphism in exon 2 and the isoleucine to threonine polymorphism at codon 56 of MnSOD were determined by a polymerase chain reaction-restriction fragment length polymorphism technique in 213 patients and 209 normal controls. RESULTS: There was a significant difference in GPX1 genotype frequency between the case and control groups (p = 0.001). The adjusted OR for bladder cancer was 2.63 for the Pro/Leu genotype compared with the Pro/Pro genotype (95% CI 1.45 to 4.75, p = 0.001). Compared with the Pro/Pro genotype the Pro/Leu genotype was significantly associated with advanced tumor stage (Ta-1 vs T2-4, OR 2.58, 95% CI 1.07 to 6.18, p = 0.034) but not with tumor grade. Analysis of the MnSOD polymorphism provided no significant results. However, in men with at least 1 Ala MnSOD allele the risk associated with the Pro/Leu GPX1 genotype increased up to 6.31 (95% CI 1.28 to 31.24, p = 0.024). CONCLUSIONS: The GPX1 Pro/Leu genotype may significantly increase the risk of bladder cancer and the increased risk may be modified by the Ala-9Val MnSOD polymorphism. The GPX1 genotype may further affect the disease status of bladder cancer.

Aged↗