Although the association of genetic polymorphisms in glutathione S-transferase(GST) and N-acetyltransferase(NAT) with bladder cancer has been reported, limited numbers of studies have been indicated the association of CYP2E1 with bladder cancer, particularly in Asian population. A hospital based case-control study was conducted in South Korean, consisting of 232 histologically confirmed prevalent bladder cancer cases and 165 controls to evaluate the association between genetic polymorphisms of CYP2E1(RsaI) and development of bladder cancer. The frequency of CYP2E1(RsaI) c1/c1 genotype in bladder cancer cases was higher than in controls; 114 of 201(56.7%) vs. 62 of 146(42.5%). Men with CYP2E1(RsaI) c1/c1 genotype had increased risk of development of bladder cancer compared to men with at least one c2 allele(OR=1.7, 95% CI=1.1-2.7). The bladder cancer risk increased as the number of c1 allele increased(p for trend=0.005). The risk increased as the amount of smoking increased(p for trend=0.009). When data were analyzed for the interaction between smoking and CYP2E1 genetic polymorphisms, smokers with c1/c1 genotype have 2.5 greater risk in development of bladder cancer(95% CI=1.0-6.2) compared to nonsmokers with c2 allele(p for interaction=0.008). Our findings suggest that the interaction between genetic polymorphisms of CYP 2E1 (RsaI, c1/c1) and smoking may play an important role for development of bladder cancer among Koreans.
Alleles ; Asian Continental Ancestry Group ; Case-Control Studies ; Cytochrome P-450 CYP2E1* ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Genotype ; Glutathione ; Humans ; Korea* ; Male ; Polymorphism, Genetic* ; Smoke ; Smoking ; Urinary Bladder Neoplasms* ; Urinary Bladder*

PURPOSE: The purpose of this study was to elucidate prognostic factors for survival and clinical outcomes of rological soft tissue sarcomas (STSs). MATERIALS AND METHODS: This was a retrospective review of the medical records of 48 patients with urological STS treated from January 1982 to July 2009. Demographic and pathological characteristics were compared. Patients' demographics, clinico-pathological parameters, overall survival, and the factors expected to predict survival, such as sex, age at diagnosis, primary organ, surgical resection, metastasis, and mass size, were analyzed. We evaluated differences in survival on the basis of histological subtype by Kaplan-Meier analysis and multivariate Cox proportional hazards regression. RESULTS: The study included 34 males (70.8%) and 14 females (29.1%). The mean age at diagnosis was 47.1 years (range, 3 to 80). The most common site was the retroperitoneum (n=16), followed by the kidney (n=12), prostate (n=10), bladder (n=7), ureter (n=1), and paratesticular region (n=1). Nineteen patients (39.5%) had other organ metastases at diagnosis. The most common subtypes of sarcoma were leiomyosarcoma (50%), rhabdomyosarcoma (18.7%), and liposarcoma (8%). The remaining 11 cases had other histological subtypes (22.9%). Mean tumor size was 9.5 cm (range, 2.2 to 24). Thirty-three patients (68.7%) underwent surgical resection. The overall survival rate at 5 years was 51.4%. In the univariate and multivariate analysis, surgical resection, primary tumor site, and metastasis at diagnosis remained significant predictors of prognosis. Patients with retroperitoneal sarcoma had a higher overall survival rate by 5 years compared with patients with other organ sarcoma. CONCLUSIONS: The overall survival rate at 5 years was 51.4%. Surgical resection, primary tumor site, and metastasis at diagnosis remained significant predictors of prognosis.
Demography ; Female ; Humans ; Kaplan-Meier Estimate ; Kidney ; Leiomyosarcoma ; Liposarcoma ; Male ; Medical Records ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Prostate ; Retrospective Studies ; Rhabdomyosarcoma ; Sarcoma ; Survival Rate ; Ureter ; Urinary Bladder

Background/Aims: Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD. Methods: Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing. Results: Methylome and transcriptome analyses of liver biopsies revealed significant (p<0.05) hypermethylation and downregulation of C1R, C1S, C3, C6, C4BPA<, and SERPING1, as well as hypomethylation (p<0.0005) and upregulation (p<0.05) of C5AR1, C7, and CD59, in association with the histological severity of MASLD. Furthermore, DNA methylation and the relative expression of nine complement genes in a MASH diet mouse model aligned with human data. Conclusions Our research provides compelling evidence that epigenetic alterations in complement genes correlate with MASLD severity, offering valuable insights into the mechanisms driving MASLD progression, and suggests that inhibiting the function of certain complement proteins may be a promising strategy for managing MASLD.

Background/Aims: Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD. Methods: Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing. Results: Methylome and transcriptome analyses of liver biopsies revealed significant (p<0.05) hypermethylation and downregulation of C1R, C1S, C3, C6, C4BPA<, and SERPING1, as well as hypomethylation (p<0.0005) and upregulation (p<0.05) of C5AR1, C7, and CD59, in association with the histological severity of MASLD. Furthermore, DNA methylation and the relative expression of nine complement genes in a MASH diet mouse model aligned with human data. Conclusions Our research provides compelling evidence that epigenetic alterations in complement genes correlate with MASLD severity, offering valuable insights into the mechanisms driving MASLD progression, and suggests that inhibiting the function of certain complement proteins may be a promising strategy for managing MASLD.

Background/Aims: Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD. Methods: Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing. Results: Methylome and transcriptome analyses of liver biopsies revealed significant (p<0.05) hypermethylation and downregulation of C1R, C1S, C3, C6, C4BPA<, and SERPING1, as well as hypomethylation (p<0.0005) and upregulation (p<0.05) of C5AR1, C7, and CD59, in association with the histological severity of MASLD. Furthermore, DNA methylation and the relative expression of nine complement genes in a MASH diet mouse model aligned with human data. Conclusions Our research provides compelling evidence that epigenetic alterations in complement genes correlate with MASLD severity, offering valuable insights into the mechanisms driving MASLD progression, and suggests that inhibiting the function of certain complement proteins may be a promising strategy for managing MASLD.

Background/Aims: Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD. Methods: Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing. Results: Methylome and transcriptome analyses of liver biopsies revealed significant (p<0.05) hypermethylation and downregulation of C1R, C1S, C3, C6, C4BPA<, and SERPING1, as well as hypomethylation (p<0.0005) and upregulation (p<0.05) of C5AR1, C7, and CD59, in association with the histological severity of MASLD. Furthermore, DNA methylation and the relative expression of nine complement genes in a MASH diet mouse model aligned with human data. Conclusions Our research provides compelling evidence that epigenetic alterations in complement genes correlate with MASLD severity, offering valuable insights into the mechanisms driving MASLD progression, and suggests that inhibiting the function of certain complement proteins may be a promising strategy for managing MASLD.