|
1
|
Hao X, Fan R, Zeng HM, Hou JL. Hepatocellular Carcinoma Risk Scores from Modeling to Real Clinical Practice in Areas Highly Endemic for Hepatitis B Infection. J Clin Transl Hepatol 2023; 11:1508-1519. [PMID: 38161501 PMCID: PMC10752803 DOI: 10.14218/jcth.2023.00087] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/04/2023] [Accepted: 06/02/2023] [Indexed: 01/03/2024] Open
Abstract
Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and represents a global health challenge. Liver cancer ranks third in cancer-related mortality with 830,000 deaths and sixth in incidence with 906,000 new cases annually worldwide. HCC most commonly occurs in patients with underlying liver disease, especially chronic hepatitis B virus (HBV) infection in highly endemic areas. Predicting HCC risk based on scoring models for patients with chronic liver disease is a simple, effective strategy for identifying and stratifying patients to improve the early diagnosis rate and prognosis of HCC. We examined 23 HCC risk scores published worldwide in CHB patients with (n=10) or without (n=13) antiviral treatment. We also described the characteristics of the risk score's predictive performance and application status. In the future, higher predictive accuracy could be achieved by combining novel technologies and machine learning algorithms to develop and update HCC risk score models and integrated early warning and diagnosis systems for HCC in hospitals and communities.
Collapse
Affiliation(s)
- Xin Hao
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
| | - Rong Fan
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
| | - Hong-Mei Zeng
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jin-Lin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
| |
Collapse
|
|
2
|
Shoukat A, Nurulain SM, Hussain S, Khan SA, Ahmed H, Muneer Z, Abbas Shah ST, Raza S, Eqani SAMS. Chronic exposure to electronic waste poses risk to liver toxicity with molecular interaction of GSTM1, GSTT1 null variants, and GSTP1. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 334:122204. [PMID: 37453685 DOI: 10.1016/j.envpol.2023.122204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 07/11/2023] [Accepted: 07/12/2023] [Indexed: 07/18/2023]
Abstract
Chronic exposure to electronic waste (e-waste) is becoming a serious concern for health among individuals exposed to it. E-waste has been reported to contain heavy metals, trace elements, and persistent organic pollutants which can trigger health issues through different biological pathways. The liver is a major metabolic and detoxifying organ in the body. Glutathione S-transferase (GST) is a liver enzyme for phase II detoxification that catalyzes glutathione (GSH) conjugation with environmental pollutants. This research aimed to investigate the liver toxicity caused by long-term exposure to e-wastes, exploring the potential association with null variants of GSTT1 and GSTMI, as well as GSTP1. The study was designed as a cross-sectional investigation, in which 256 adult males who were chronically exposed to e-waste and 200 non-exposed control participants, matched for age and gender, were recruited randomly. Standard colorimetric and enzymatic methods were used to analyze biochemical parameters such as serum alkaline phosphatase (ALP), alanine transaminase (ALT), total bilirubin (T. Bil), albumin, and reduced glutathione. Genotypic analysis of the null variant GSTM1, GSTT1, and GSTP1 genes was conducted by standard molecular methods. The study findings indicated a notable surge in ALP, ALT, and albumin levels while T. Bil and GSH levels showed a reduction, suggesting a potential risk of liver toxicity. Additionally, analysis of GSTM1, GSTT1, and GSTP1 genotypes revealed a possible association with GSH levels and the hepatotoxicity risk. The study concluded that the individuals exposed to e-waste exhibited dysregulation of liver enzymes that results in liver toxicity. Moreover, analysis of GSTM1, GSTT1, and GSTP1 at a molecular level revealed that these genes could potentially serve as risk factors for liver toxicity in e-waste chronic exposure.
Collapse
Affiliation(s)
- Aneela Shoukat
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Park Road Tarlai, Islamabad, 45550, Pakistan
| | - Syed Muhammad Nurulain
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Park Road Tarlai, Islamabad, 45550, Pakistan.
| | - Sabir Hussain
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Park Road Tarlai, Islamabad, 45550, Pakistan
| | - Sosan Andleeb Khan
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Park Road Tarlai, Islamabad, 45550, Pakistan
| | - Hussain Ahmed
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Park Road Tarlai, Islamabad, 45550, Pakistan
| | - Zahid Muneer
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Park Road Tarlai, Islamabad, 45550, Pakistan
| | - Syed Tahir Abbas Shah
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Park Road Tarlai, Islamabad, 45550, Pakistan
| | - Saqlain Raza
- Respiratory Care Department, College of Applied Medical Science in Jubail, Imam Abdulrahman Bin Faisal University, Jubail, Saudi Arabia
| | - Syed Ali Musstjab Shah Eqani
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Park Road Tarlai, Islamabad, 45550, Pakistan
| |
Collapse
|
|
3
|
Amgalan B, Day CP, Przytycka TM. Exploring tumor-normal cross-talk with TranNet: Role of the environment in tumor progression. PLoS Comput Biol 2023; 19:e1011472. [PMID: 37721939 PMCID: PMC10538798 DOI: 10.1371/journal.pcbi.1011472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 09/28/2023] [Accepted: 08/23/2023] [Indexed: 09/20/2023] Open
Abstract
There is a growing awareness that tumor-adjacent normal tissues used as control samples in cancer studies do not represent fully healthy tissues. Instead, they are intermediates between healthy tissues and tumors. The factors that contribute to the deviation of such control samples from healthy state include exposure to the tumor-promoting factors, tumor-related immune response, and other aspects of tumor microenvironment. Characterizing the relation between gene expression of tumor-adjacent control samples and tumors is fundamental for understanding roles of microenvironment in tumor initiation and progression, as well as for identification of diagnostic and prognostic biomarkers for cancers. To address the demand, we developed and validated TranNet, a computational approach that utilizes gene expression in matched control and tumor samples to study the relation between their gene expression profiles. TranNet infers a sparse weighted bipartite graph from gene expression profiles of matched control samples to tumors. The results allow us to identify predictors (potential regulators) of this transition. To our knowledge, TranNet is the first computational method to infer such dependencies. We applied TranNet to the data of several cancer types and their matched control samples from The Cancer Genome Atlas (TCGA). Many predictors identified by TranNet are genes associated with regulation by the tumor microenvironment as they are enriched in G-protein coupled receptor signaling, cell-to-cell communication, immune processes, and cell adhesion. Correspondingly, targets of inferred predictors are enriched in pathways related to tissue remodelling (including the epithelial-mesenchymal Transition (EMT)), immune response, and cell proliferation. This implies that the predictors are markers and potential stromal facilitators of tumor progression. Our results provide new insights into the relationships between tumor adjacent control sample, tumor and the tumor environment. Moreover, the set of predictors identified by TranNet will provide a valuable resource for future investigations.
Collapse
Affiliation(s)
- Bayarbaatar Amgalan
- National Center for Biotechnology Information/National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Chi-Ping Day
- Laboratory of Cancer Biology and Genetics/Center for Cancer Research/National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Teresa M. Przytycka
- National Center for Biotechnology Information/National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America
| |
Collapse
|
|
4
|
Amgalan B, Day CP, Przytycka TM. Exploring tumor-normal cross-talk with TranNet: role of the environment in tumor progression. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.02.24.529899. [PMID: 36945455 PMCID: PMC10028821 DOI: 10.1101/2023.02.24.529899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/27/2023]
Abstract
There is a growing awareness that tumor-adjacent normal tissues used as control samples in cancer studies do not represent fully healthy tissues. Instead, they are intermediates between healthy tissues and tumors. The factors that contribute to the deviation of such control samples from healthy state include exposure to the tumor-promoting factors, tumor-related immune response, and other aspects of tumor microenvironment. Characterizing the relation between gene expression of tumor-adjacent control samples and tumors is fundamental for understanding roles of microenvironment in tumor initiation and progression, as well as for identification of diagnostic and prognostic biomarkers for cancers. To address the demand, we developed and validated TranNet, a computational approach that utilizes gene expression in matched control and tumor samples to study the relation between their gene expression profiles. TranNet infers a sparse weighted bipartite graph from gene expression profiles of matched control samples to tumors. The results allow us to identify predictors (potential regulators) of this transition. To our knowledge, TranNet is the first computational method to infer such regulation. We applied TranNet to the data of several cancer types and their matched control samples from The Cancer Genome Atlas (TCGA). Many predictors identified by TranNet are genes associated with regulation by the tumor microenvironment as they are enriched in G-protein coupled receptor signaling, cell-to-cell communication, immune processes, and cell adhesion. Correspondingly, targets of inferred predictors are enriched in pathways related to tissue remodelling (including the epithelial-mesenchymal Transition (EMT)), immune response, and cell proliferation. This implies that the predictors are markers and potential stromal facilitators of tumor progression. Our results provide new insights for the relationships between tumor adjacent control sample, tumor and the tumor environment. Moreover, the set of predictors identified by TranNet will provide a valuable resource for future investigations. The TranNet method was implemented in python, source codes and the data sets used for and generated during this study are available at the Github site https://github.com/ncbi/TranNet .
Collapse
Affiliation(s)
- Bayarbaatar Amgalan
- National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, Maryland, USA
| | - Chi-Ping Day
- Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Teresa M. Przytycka
- National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, Maryland, USA
| |
Collapse
|
|
5
|
Damaskos C, Garmpis N, Dimitroulis D, Garmpi A, Psilopatis I, Sarantis P, Koustas E, Kanavidis P, Prevezanos D, Kouraklis G, Karamouzis MV, Marinos G, Kontzoglou K, Antoniou EA. Targeted Therapies for Hepatocellular Carcinoma Treatment: A New Era Ahead-A Systematic Review. Int J Mol Sci 2022; 23:ijms232214117. [PMID: 36430594 PMCID: PMC9698799 DOI: 10.3390/ijms232214117] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/10/2022] [Accepted: 11/11/2022] [Indexed: 11/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) remains one of the most common malignancies and the third cause of cancer-related death worldwide, with surgery being the best prognostic tool. Among the well-known causative factors of HCC are chronic liver virus infections, chronic virus hepatitis B (HBV) and chronic hepatitis virus C (HCV), aflatoxins, tobacco consumption, and non-alcoholic liver disease (NAFLD). There is a need for the development of efficient molecular markers and alternative therapeutic targets of great significance. In this review, we describe the general characteristics of HCC and present a variety of targeted therapies that resulted in progress in HCC therapy.
Collapse
Affiliation(s)
- Christos Damaskos
- Renal Transplantation Unit, Laiko General Hospital, 11527 Athens, Greece
- Nikolaos Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
- Correspondence: ; Tel.: +30-694-846-7790
| | - Nikolaos Garmpis
- Nikolaos Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
- Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Dimitrios Dimitroulis
- Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Anna Garmpi
- First Department of Propedeutic Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Iason Psilopatis
- Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt—Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Panagiotis Sarantis
- Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Evangelos Koustas
- Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Prodromos Kanavidis
- Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | | | - Gregory Kouraklis
- Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Michail V. Karamouzis
- Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Georgios Marinos
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Konstantinos Kontzoglou
- Nikolaos Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
- Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Efstathios A. Antoniou
- Nikolaos Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
- Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| |
Collapse
|
|
6
|
Kadiri DD, Peela S, Ganguli D. Effect of cirrhosis and hepatitis on the prognosis of liver cancer. THERANOSTICS AND PRECISION MEDICINE FOR THE MANAGEMENT OF HEPATOCELLULAR CARCINOMA 2022:51-72. [DOI: 10.1016/b978-0-323-98806-3.00002-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
7
|
Chen Q, Ren Z, Liu D, Jin Z, Wang X, Zhang R, Liu Q, Cheng W. Identification of prognostic metabolic genes in adrenocortical carcinoma and establishment of a prognostic nomogram: A bioinformatic study. Medicine (Baltimore) 2021; 100:e27864. [PMID: 34918636 PMCID: PMC10545245 DOI: 10.1097/md.0000000000027864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 10/09/2021] [Accepted: 11/03/2021] [Indexed: 11/26/2022] Open
Abstract
ABSTRACT Adrenocortical carcinoma is an invasive malignancy with poor prognosis, high recurrence rate and limited therapeutic options. Therefore, it is necessary to establish an effective method to diagnose and evaluate the prognosis of patients, so as to realize individualized treatment and improve their survival rate.This study investigated metabolic genes that may be potential therapeutic targets for Adrenocortical carcinoma (ACC). Level 3 gene expression data from the ACC cohort and the relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. To verify, other ACC datasets (GSE76021, GSE19750) were downloaded from the Gene Expression Omnibus (GEO) database. The ACC datasets from TCGA and GEO were used to screen metabolic genes through the Molecular Signatures Database using gene set enrichment analysis. Then, the overlapping metabolic genes of the 2 datasets were identified.A signature of five metabolic genes (CYP11B1, GSTM2, IRF9, RPL31, and UBE2C) was identified in patients with ACC. The signature could be used to divide the patients with ACC into high- and low-risk groups based on their median risk score. Multivariate Cox regression analysis was performed to determine the independent prognostic factors of ACC. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to assess the prediction accuracy of the prognostic signature. Last, a nomogram was established to assess the individualized prognosis prediction model.The results indicated that the signature of 5 metabolic genes had excellent predictive value for ACC. These findings might help improve personalized treatment and medical decisions.
Collapse
Affiliation(s)
- Qing Chen
- Department of Endocrinology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ziyu Ren
- Department of Endocrinology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dongfang Liu
- Department of Endocrinology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | | | - Xuan Wang
- Department of Endocrinology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Rui Zhang
- Department of Endocrinology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qicong Liu
- Department of Endocrinology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei Cheng
- Department of Endocrinology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| |
Collapse
|
|
8
|
Ren X, Ma L, Wang N, Zhou R, Wu J, Xie X, Zhang H, Liu D, Ma X, Dang C, Kang H, Zhou Z. Antioxidant Gene Signature Impacts the Immune Infiltration and Predicts the Prognosis of Kidney Renal Clear Cell Carcinoma. Front Genet 2021; 12:721252. [PMID: 34490047 PMCID: PMC8416991 DOI: 10.3389/fgene.2021.721252] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 07/30/2021] [Indexed: 01/05/2023] Open
Abstract
Background: Oxidative stress is related to oncogenic transformation in kidney renal clear cell carcinoma (KIRC). We intended to identify a prognostic antioxidant gene signature and investigate its relationship with immune infiltration in KIRC. Methods: With the support of The Cancer Genome Atlas (TCGA) database, we researched the gene expression and clinical data of KIRC patients. Antioxidant related genes with significant differences in expression between KIRC and normal samples were then identified. Through univariate and multivariate Cox analysis, a prognostic gene model was established and all patients were divided into high- and low-risk subgroups. Single sample gene set enrichment analysis was adopted to analyze the immune infiltration, HLA expression, and immune checkpoint genes in different risk groups. Finally, the prognostic nomogram model was established and evaluated. Results: We identified six antioxidant genes significantly correlated with the outcome of KIRC patients as independent predictors, namely DPEP1 (HR = 0.97, P < 0.05), GSTM3 (HR = 0.97, P < 0.05), IYD (HR = 0.33, P < 0.05), KDM3B (HR = 0.96, P < 0.05), PRDX2 (HR = 0.99, P < 0.05), and PRXL2A (HR = 0.96, P < 0.05). The high- and low-risk subgroups of KIRC patients were grouped according to the six-gene signature. Patients with higher risk scores had poorer prognosis, more advanced grade and stage, and more abundance of M0 macrophages, regulatory T cells, and follicular helper T cells. There were statistically significant differences in HLA and checkpoint gene expression between the two risk subgroups. The performance of the nomogram was favorable (concordance index = 0.766) and reliably predicted the 3-year (AUC = 0.792) and 5-year (AUC = 0.766) survival of patients with KIRC. Conclusion: The novel six antioxidant related gene signature could effectively forecast the prognosis of patients with KIRC, supply insights into the interaction between cellular antioxidant mechanisms and cancer, and is an innovative tool for selecting potential patients and targets for immunotherapy.
Collapse
Affiliation(s)
- Xueting Ren
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Li Ma
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Nan Wang
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ruina Zhou
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jianhua Wu
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xin Xie
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Hao Zhang
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Di Liu
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaobin Ma
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Chengxue Dang
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Huafeng Kang
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhangjian Zhou
- Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| |
Collapse
|
|
9
|
Prysyazhnyuk V, Sydorchuk L, Sydorchuk R, Prysiazhniuk I, Bobkovych K, Buzdugan I, Dzuryak V, Prysyazhnyuk P. Glutathione-S-transferases genes-promising predictors of hepatic dysfunction. World J Hepatol 2021; 13:620-633. [PMID: 34239698 PMCID: PMC8239493 DOI: 10.4254/wjh.v13.i6.620] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/06/2021] [Accepted: 06/03/2021] [Indexed: 02/06/2023] Open
Abstract
One of the most commonly known genes involved in chronic diffuse liver diseases pathogenesis are genes that encodes the synthesis of glutathione-S-transferase (GST), known as the second phase enzyme detoxification system that protects against endogenous oxidative stress and exogenous toxins, through catalisation of glutathione sulfuric groups conjugation and decontamination of lipid and deoxyribonucleic acid oxidation products. The group of GST enzymes consists of cytosolic, mitochondrial and microsomal fractions. Recently, eight classes of soluble cytoplasmic isoforms of GST enzymes are widely known: α-, ζ-, θ-, κ-, μ-, π-, σ-, and ω-. The GSTs gene family in the Human Gene Nomenclature Committee, online database recorded over 20 functional genes. The level of GSTs expression is considered to be a crucial factor in determining the sensitivity of cells to a broad spectrum of toxins. Nevertheless, human GSTs genes have multiple and frequent polymorphisms that include the complete absence of the GSTM1 or the GSTT1 gene. Current review supports the position that genetic polymorphism of GST genes is involved in the pathogenesis of various liver diseases, particularly non-alcoholic fatty liver disease, hepatitis and liver cirrhosis of different etiology and hepatocellular carcinoma. Certain GST allelic variants were proven to be associated with susceptibility to hepatological pathology, and correlations with the natural course of the diseases were subsequently postulated.
Collapse
Affiliation(s)
- Vasyl Prysyazhnyuk
- Department of Propedeutics of Internal Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Larysa Sydorchuk
- Department of Family Medicine, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Ruslan Sydorchuk
- Department of Surgery, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Iryna Prysiazhniuk
- Department of Internal Medicine and Invectious Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Kateryna Bobkovych
- Department of Propedeutics of Internal Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Inna Buzdugan
- Department of Internal Medicine and Invectious Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Valentina Dzuryak
- Department of Family Medicine, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Petro Prysyazhnyuk
- Department of Medical and Pharmaceutical Chemistry, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| |
Collapse
|
|
10
|
Ferreira GD, Fernandes GMDM, Penteado C, Cória VR, Galbiatti-Dias ALDS, Russo A, Castanhole-Nunes MMU, Silva RFD, Silva RDCMAD, Pavarino ÉC, Torreglosa Ruiz Cintra M, Goloni-Bertollo EM. Polymorphisms in xenobiotic metabolism-related genes in patients with hepatocellular carcinoma: a case-control study. Xenobiotica 2021; 51:737-744. [PMID: 33896378 DOI: 10.1080/00498254.2021.1893408] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This study was performed to investigate the relationship between polymorphisms in microsomal epoxide hydrolase (mEH; Tyr113His and His139Arg substitution) and glutathione S-transferase (GST; GSTM1 deletion, GSTT1 deletion, and GSTP1.Ala114Val substitution) and their correlation with clinico-histopathological features in hepatocellular carcinoma (HCC).We evaluated environmental risk factors and genetic alterations in 556 individuals (86 cases and 470 controls). PCR multiplex for GSTM1 and GSTT1, polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for GSTP1, and real-time PCR for mEH were performed. Statistical analyses were performed using multiple logistic regression tests.Age over 48 years (p < 0.001) and alcohol consumption (p = 0.021) were the predictors of increased risk of developing HCC. GSTP1.Ala114Val for all regression models (p < 0.05), except the recessive model, and the GSTT1 null genotype (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.21-0.87, p = 0.019) were predictors of an increased risk of developing HCC. Polymorphic GSTT1, GSTM1, GSTP1.Ala114Val, and mEH.His139Arg and wild-type mEH.Tyr113His (OR = 5.04; 95% CI = 1.59-16.04; p = 0.006) were associated with HCC.Age over 48 years, alcohol consumption, and the presence of polymorphic variants of GSTP1 and GSTT1 were associated with the risk of developing HCC.
Collapse
Affiliation(s)
- Gislaine Dionísio Ferreira
- Molecular Biology Department, Genetics and Molecular Biology Research Unit - UPGEM, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto, Brazil
| | - Glaucia Maria de Mendonça Fernandes
- Molecular Biology Department, Genetics and Molecular Biology Research Unit - UPGEM, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto, Brazil
| | - Camila Penteado
- Molecular Biology Department, Genetics and Molecular Biology Research Unit - UPGEM, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto, Brazil
| | - Vivian Romanholi Cória
- Molecular Biology Department, Genetics and Molecular Biology Research Unit - UPGEM, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto, Brazil
| | - Ana Lívia da Silva Galbiatti-Dias
- Molecular Biology Department, Genetics and Molecular Biology Research Unit - UPGEM, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto, Brazil.,São José do Rio Preto Regional Medical School Foundation - FUNFARME, São José do Rio Preto, Brazil
| | - Anelise Russo
- Molecular Biology Department, Genetics and Molecular Biology Research Unit - UPGEM, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto, Brazil
| | - Márcia Maria Urbanin Castanhole-Nunes
- Molecular Biology Department, Genetics and Molecular Biology Research Unit - UPGEM, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto, Brazil.,São José do Rio Preto Regional Medical School Foundation - FUNFARME, São José do Rio Preto, Brazil
| | - Renato Ferreira da Silva
- Study Group of Liver Tumors - GETF, Surgery Department, São José do Rio Preto Medical School Fundation - FAMERP/FUNFARME, São José do Rio Preto, Brazil.,São José do Rio Preto Regional Medical School Foundation - FUNFARME, São José do Rio Preto, Brazil
| | - Rita de Cássia Martins Alves da Silva
- Study Group of Liver Tumors - GETF, Surgery Department, São José do Rio Preto Medical School Fundation - FAMERP/FUNFARME, São José do Rio Preto, Brazil.,São José do Rio Preto Regional Medical School Foundation - FUNFARME, São José do Rio Preto, Brazil
| | - Érika Cristina Pavarino
- Molecular Biology Department, Genetics and Molecular Biology Research Unit - UPGEM, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto, Brazil.,São José do Rio Preto Regional Medical School Foundation - FUNFARME, São José do Rio Preto, Brazil
| | | | - Eny Maria Goloni-Bertollo
- Molecular Biology Department, Genetics and Molecular Biology Research Unit - UPGEM, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto, Brazil.,São José do Rio Preto Regional Medical School Foundation - FUNFARME, São José do Rio Preto, Brazil
| |
Collapse
|
|
11
|
Sánchez-Siles M, Pelegrín-Hernández JP, Hellin-Meseguer D, Guerrero-Sánchez Y, Corno-Caparrós A, Cabezas-Herrera J, Pastor-Quirante F, Fernández-Ruiz JA, Aliaga-Sánchez A, Lucero-Berdugo M, Camacho-Alonso F. Genotype of Null Polymorphisms in Genes GSTM1, GSTT1, CYP1A1, and CYP1A1*2A (rs4646903 T>C)/CYP1A1*2C (rs1048943 A>G) in Patients with Larynx Cancer in Southeast Spain. Cancers (Basel) 2020; 12:cancers12092478. [PMID: 32882964 PMCID: PMC7563952 DOI: 10.3390/cancers12092478] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 08/19/2020] [Accepted: 08/27/2020] [Indexed: 01/08/2023] Open
Abstract
Simple Summary Epidemiological studies have shown that individual susceptibility to cancer is mediated by genetic and environmental factors. The aim of the present study is to evaluate the individuals’ metabolic genetic susceptibility to toxic habits (smoking and alcohol consumption) by detecting polymorphisms CYP1A1 rs1048943 T>C and CYPA1A2 rs4646903 A>G, and null polymorphisms in GSTM1 and GSTT1 genotypes, comparing a group of healthy control subjects with a population of larynx cancer patients from southeastern Spain. As results patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms. Abstract Background: some types of cancer have been associated with the presence of single nucleotide polymorphisms (SNPs) of some genes that encode enzymes: glutathione-S transferase (GST), whose alteration leads to loss of function and a lower capacity to eliminate toxic GSTM1 and GSTT1 null genotypes; SNPs causing loss of function of CYP1A1 or CYP1A1–2 cytochrome P450 enzymes related with a lower capacity to deactivate hydrocarbons related to smoking, which involves a higher risk of developing some smoking-dependent cancers including larynx cancer. Objective: to compare the presence of null SNPs in genes GSTM1, GSTT1, and CYP1A1 rs 4646903 T>C, and CYP1A1–2 RS1048943 A>G in patients with hypopharyngeal and larynx cancer with a healthy control group. Materials and method: The study included a total of 80 patients with hypopharyngeal and laryngeal cancer and 23 healthy subjects. Genomic DNA was obtained from saliva samples, determining genotype GSTM1 (present +, or null −), GSTT1 (present + or null −). Polymorphisms (SNP) in CYP1A1 T>C (present + CC, or absent − TC/TT), and CYP1A1–2 A>G (present + GG, or absent − AG/AA). Results: the mean age of patients with larynx cancer was 62 years and of control subjects 63 years. Of the total sample, over 95% were men, and over 90% were smokers. The presence of null genotypes for GTM1 was 50% in patients with larynx cancer (p = 0.042), while GSTT1 was 88.75% (p = 0.002). CYP1A1 rs4646903 T>C polymorphisms were detected in 100% of cases of larynx cancer and 17.39% of healthy subjects (p > 0.001). Conclusions: patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms.
Collapse
Affiliation(s)
| | | | - Diego Hellin-Meseguer
- Otorhinolaryngology, University Hospital Virgen de la Arrixaca, 30005 Murcia, Spain; (J.P.P.-H.); (D.H.-M.)
| | - Yolanda Guerrero-Sánchez
- Department of Human Anatomy and Psychobiology, University of Murcia, 30100 Murcia, Spain
- Correspondence:
| | | | - Juan Cabezas-Herrera
- Molecular Therapy and Biomarkers Research Group, Clinical Analysis Service, IMIB, 30005 Murcia, Spain;
| | | | | | | | - Mayra Lucero-Berdugo
- Department of Oral Medicine, Catholic University of Murcia, 30107 Murcia, Spain;
| | | |
Collapse
|
|
12
|
Glutathione S-transferase T1 and M1 null genotype distribution among non-alcoholic fatty liver disease patients and its association with cytokine and adipokine profiles. Clin Exp Hepatol 2020; 6:142-149. [PMID: 32728632 PMCID: PMC7380472 DOI: 10.5114/ceh.2020.95678] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Accepted: 04/18/2020] [Indexed: 12/20/2022] Open
Abstract
Aim of the study Among the key genes involved in the development of non-alcoholic fatty liver disease (NAFLD) are genes encoding the synthesis of glutathione S-transferase (GST). Material and methods Deletion polymorphism of GSTT1 and GSTM1 genes was investigated in 104 NAFLD patients and 45 healthy individuals. Biochemical blood analysis, tumor necrosis factor-α (TNF-α), interleukin-10, leptin and adiponectin plasma levels were studied. Results The distribution of deletion vs. non-deletion genotypes of the GSTT1 gene in NAFLD patients was 18 (17.3%) vs. 86 (82.7%) patients and in healthy people it was 6 (13.3%) vs. 39 (86.7%) individuals. The genotype distribution of the GSTM1 gene was as follows: 52 (50.0%) NAFLD patients had null genotype vs. 52 patients (50.0%) with non-deletion genotype; in the control group - 23 (51.1%) vs. 22 (48.9%) individuals. Deletion of the GSTT1 gene in NAFLD patients was associated with twice as high (p = 0.01) TNF-α level in the blood as compared to patients with normal genotype. Higher concentration of leptin in blood by 37.1% (p = 0.04) was observed in patients with null genotype of the GSTM1 gene, as compared to those with normal genotype. Conclusions Deletion polymorphism of GSTT1 and GSTM1 genes distribution among NAFLD patients did not differ as compared to healthy individuals. Null-genotype GSTT1 gene carriers were characterized by higher TNF-α concentration and null-genotype GSTM1 gene carriers were characterized by elevated leptin level as compared to normal genotype carriers.
Collapse
|
|
13
|
Carrot-Zhang J, Chambwe N, Damrauer JS, Knijnenburg TA, Robertson AG, Yau C, Zhou W, Berger AC, Huang KL, Newberg JY, Mashl RJ, Romanel A, Sayaman RW, Demichelis F, Felau I, Frampton GM, Han S, Hoadley KA, Kemal A, Laird PW, Lazar AJ, Le X, Oak N, Shen H, Wong CK, Zenklusen JC, Ziv E, Cherniack AD, Beroukhim R. Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer. Cancer Cell 2020; 37:639-654.e6. [PMID: 32396860 PMCID: PMC7328015 DOI: 10.1016/j.ccell.2020.04.012] [Citation(s) in RCA: 185] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 12/31/2019] [Accepted: 04/13/2020] [Indexed: 12/11/2022]
Abstract
We evaluated ancestry effects on mutation rates, DNA methylation, and mRNA and miRNA expression among 10,678 patients across 33 cancer types from The Cancer Genome Atlas. We demonstrated that cancer subtypes and ancestry-related technical artifacts are important confounders that have been insufficiently accounted for. Once accounted for, ancestry-associated differences spanned all molecular features and hundreds of genes. Biologically significant differences were usually tissue specific but not specific to cancer. However, admixture and pathway analyses suggested some of these differences are causally related to cancer. Specific findings included increased FBXW7 mutations in patients of African origin, decreased VHL and PBRM1 mutations in renal cancer patients of African origin, and decreased immune activity in bladder cancer patients of East Asian origin.
Collapse
Affiliation(s)
- Jian Carrot-Zhang
- The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA
| | | | - Jeffrey S Damrauer
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | | | - A Gordon Robertson
- British Columbia Cancer Agency, Genome Sciences Centre, Vancouver, BC V5Z4S6, Canada
| | - Christina Yau
- Buck Institute for Research on Aging, Novato, CA 94945, USA; Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, USA
| | - Wanding Zhou
- Van Andel Research Institute, Grand Rapids, MI 49503, USA
| | - Ashton C Berger
- The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
| | - Kuan-Lin Huang
- Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | | | - R Jay Mashl
- Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
| | - Alessandro Romanel
- Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Povo (Trento), Italy
| | - Rosalyn W Sayaman
- Department of Laboratory Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
| | - Francesca Demichelis
- Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Povo (Trento), Italy
| | - Ina Felau
- National Cancer Institute, Bethesda, MD 20892, USA
| | | | - Seunghun Han
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA
| | - Katherine A Hoadley
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Anab Kemal
- National Cancer Institute, Bethesda, MD 20892, USA
| | - Peter W Laird
- Van Andel Research Institute, Grand Rapids, MI 49503, USA
| | - Alexander J Lazar
- Departments of Pathology, Genomic Medicine, and Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Xiuning Le
- Department of Thoracic and Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Ninad Oak
- Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
| | - Hui Shen
- Van Andel Research Institute, Grand Rapids, MI 49503, USA
| | - Christopher K Wong
- UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
| | | | - Elad Ziv
- Department of Laboratory Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA
| | | | - Andrew D Cherniack
- The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
| | - Rameen Beroukhim
- The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
| |
Collapse
|
|
14
|
Banerjee BD, Kumar R, Thamineni KL, Shah H, Thakur GK, Sharma T. Effect of Environmental Exposure and Pharmacogenomics on Drug Metabolism. Curr Drug Metab 2020; 20:1103-1113. [PMID: 31933442 DOI: 10.2174/1389200221666200110153304] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 11/02/2019] [Accepted: 01/03/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Pesticides are major xenobiotic compounds and environmental pollutants, which are able to alter drug-metabolizing enzyme as well as pharmacokinetics of drugs. Subsequent to the release of the human genome project, genetic variations (polymorphism) become an integral part of drug development due to their influence on disease susceptibility/ progression of the disease and their impact on drug absorption, distribution, metabolism of active metabolites and finally excretion of the drug. Genetic polymorphisms crucially regulate pharmacokinetics and pharmacodynamics of drugs under the influence of physiological condition, lifestyle, as well as pathological conditions collectively. OBJECTIVE To review all the evidence concerning the effect of environmental exposure on drug metabolism with reference to pharmacogenomics. METHODS Scientific data search and review of basic, epidemiological, pharmacogenomics and pharmacokinetics studies were undertaken to evaluate the influence of environmental contaminants on drug metabolism. RESULTS Various environmental contaminants like pesticides effectively alter drug metabolism at various levels under the influence of pharmacogenomics, which interferes with pharmacokinetics of drug metabolism. Genetic polymorphism of phase I and phase II xenobiotic-metabolizing enzymes remarkably alters disease susceptibility as well as the progression of disease under the influence of various environmental contaminants at various levels. CONCLUSION Individual specific drug response may be attributed to a large variety of factors alone or in combination ranging from genetic variations (SNP, insertion, deletion, duplication etc.) to physiological setting (gender, age, body size, and ethnicity), environmental or lifestyle factors (radiation exposure, smoking, alcohol, nutrition, exposure to toxins, etc.); and pathological conditions (obesity, diabetes, liver and renal function).
Collapse
Affiliation(s)
- Basu Dev Banerjee
- Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi-110095, India
| | - Ranjeet Kumar
- Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi-110095, India
| | - Krishna Latha Thamineni
- Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi-110095, India
| | - Harendra Shah
- Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi-110095, India
| | - Gaurav Kumar Thakur
- Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi-110095, India
| | - Tusha Sharma
- Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi-110095, India
| |
Collapse
|
|
15
|
Wang LK, Yue HL, Peng XJ, Zhang SJ. GSTO1 regards as a meritorious regulator in cutaneous malignant melanoma cells. Mol Cell Probes 2019; 48:101449. [PMID: 31525447 DOI: 10.1016/j.mcp.2019.101449] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 09/12/2019] [Accepted: 09/12/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Glutathione S-transferase omega 1 (GSTO1), as a member of the glutathione S-transferase (GST) family genes, has been discovered to be up-regulated in several cancer cell lines which exhibited strong aggressiveness. However, the function of GSTO1 on cutaneous malignant melanoma (CMM) has not been illuminated. METHODS Outcome of expression level and prognosis of GSTO1 were obtained from Oncomine and TCGA database. The specific effects of GSTO1 on the characteristics and regulatory mechanism of CMM cells were demonstrated by cell counting kit-8, colony formation, flow cytometry, and transwell assays in vitro. Western blot was employed to analyze the expression of proliferating cell nuclear antigen (PCNA), p53 and epithelial-to-mesenchymal (EMT) related proteins. RESULTS We observed that GSTO1 was up-regulated in CMM samples when compared with the corresponding controls. Moreover, patients in CMM with high expression of GSTO1 were more likely to have a poor prognosis. Through in vitro experiments, silenced GSTO1 resulted in inhibition of CMM cells growth and aggressiveness, increased cell apoptosis, and blocked cell cycle. Finally, the expression of PCNA, p53 and EMT-related proteins were changed due to reduction of GSTO1. CONCLUSIONS To sum up, our outcomes exhibited that weakening GSTO1 reduced the proliferation and mobility of CMM cells, increased the apoptosis ability of CMM cells, and arrested cell cycle at G1 phase, which can be achieved by affecting the expression of PCNA, p53 and the EMT process. This discovery provided a new perspective for elucidating the mechanism of CMM, and offered theoretical support for searching clinical therapeutic targets in the future.
Collapse
Affiliation(s)
- Li-Kun Wang
- Department of Dermatology, North China University of Science and Technology Affiliated Hospital, China.
| | - Hai-Long Yue
- Department of Anesthesiology, Kailuan General Hospital, China
| | - Xiao-Jing Peng
- Department of Anesthesiology, Kailuan General Hospital, China
| | - Shu-Juan Zhang
- Department of Anesthesiology, Kailuan General Hospital, China
| |
Collapse
|
|
16
|
Dual roles of glutathione S-transferase mu 1 in the development and metastasis of hepatocellular carcinoma. Biomed Pharmacother 2019; 120:109532. [PMID: 31605953 DOI: 10.1016/j.biopha.2019.109532] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 10/02/2019] [Accepted: 10/02/2019] [Indexed: 12/20/2022] Open
Abstract
PURPOSE Reactive oxygen species (ROS) are implicated in carcinogenesis, and cellular antioxidant systems are important for detoxifying ROS and reversing oxidant-mediated modifications. Glutathione S-transferase mu (GSTM) belongs to a family of phase II detoxification enzymes that catalyze the conjugation of reduced glutathione (GSH) to a wide range of endogenous and exogenous electrophilic compounds. The genotype of GSTM1 was associated with the risk and prognosis of cancer in several meta-analyses. This study explored the function of GSTM1 in hepatocellular carcinoma (HCC). METHODS Polymerase chain reaction (PCR) and western blotting (WB) were used to detect the levels of gene and protein expression. MTS assays, Transwell assays, and flow cytometry were used to explore the function of GSTM1 in vitro. The xenograft assay and tail vein injection model were used to explore the function of GSTM1 in vivo. RESULTS The mRNA and protein expression of GSTM1 was downregulated in HCC, but the expression levels of GSTM1 were not correlated with patient survival time. In vitro, Transwell and doxorubicin (DOX)-induced apoptosis assays revealed that GSTM1 showed opposite functions in different HCC cell lines with varied TP53 genotype statuses. The overexpression of GSTM1 in the above cell lines led to a significant decrease in ROS and an increase in GSH concentration and TP53 levels, suggesting that the controversial role of GSTM1 resulted from the TP53 genotype of HCC cells. The overexpression of GSTM1 promoted cell migration and inhibited apoptosis in the MHCC-97H cell line (TP53, R249S), but inhibited cell migration and increased apoptosis in the SMMC-7721 cell line (TP53 wildtype). CONCLUSION GSTM1 down-regulation may partially account for ROS-mediated oxidative damage and HCC carcinogenesis. GSTM1 also regulates tumor progression by disrupting the ROS-TP53 axis in HCC cells with different genetic backgrounds.
Collapse
|
|
17
|
Rosa RL, Berger M, Santi L, Driemeier D, Barros Terraciano P, Campos AR, Guimarães JA, Vainstein MH, Yates JR, Beys-da-Silva WO. Proteomics of Rat Lungs Infected by Cryptococcus gattii Reveals a Potential Warburg-like Effect. J Proteome Res 2019; 18:3885-3895. [PMID: 31502459 DOI: 10.1021/acs.jproteome.9b00326] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Cryptococcus gattii is the causative agent of cryptococcosis infection that can lead to pneumonia and meningitis in immunocompetent individuals. The molecular basis of the pathogenic process and impact on the host biochemistry are poorly understood and remain largely unknown. In this context, a comparative proteomic analysis was performed to investigate the response of the host during an infection caused by C. gattii. Lungs of experimentally infected rats were analyzed by shotgun proteomics to identify differentially expressed proteins induced by C. gattii clinical strain. The proteomic results were characterized using bioinformatic tools, and subsequently, the molecular findings were validated in cell culture and lungs of infected animals. A dramatic change was observed in protein expression triggered by C. gattii infection, especially related to energy metabolism. The main pathways affected include aerobic glycolysis cycle, TCA cycle, and pyrimidine and purine metabolism. Analyses in human lung fibroblast cells confirmed the altered metabolic status found in infected lungs. Thus, it is clear that C. gattii infection triggers important changes in energy metabolism leading to the activation of glycolysis and lactate accumulation in lung cells, culminating in a cancerlike metabolic status known as the Warburg effect. The results presented here provide important insights to better understand C. gattii molecular pathogenesis.
Collapse
Affiliation(s)
- Rafael L Rosa
- Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia , Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , RS 90040-060 , Brazil.,Centro de Pesquisa Experimental, Laboratório de Bioquímica Farmacológica , Hospital de Clínicas de Porto Alegre (UFRGS) , Porto Alegre , RS 90035-007 , Brazil.,Faculdade de Farmácia , Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , RS 90610-000 , Brazil
| | - Markus Berger
- Centro de Pesquisa Experimental, Laboratório de Bioquímica Farmacológica , Hospital de Clínicas de Porto Alegre (UFRGS) , Porto Alegre , RS 90035-007 , Brazil
| | - Lucélia Santi
- Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia , Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , RS 90040-060 , Brazil.,Centro de Pesquisa Experimental, Laboratório de Bioquímica Farmacológica , Hospital de Clínicas de Porto Alegre (UFRGS) , Porto Alegre , RS 90035-007 , Brazil.,Faculdade de Farmácia , Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , RS 90610-000 , Brazil
| | - David Driemeier
- Departamento de Patologia Clínica Veterinária, Faculdade de Medicina Veterinária , Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , RS 91540-000 , Brazil
| | - Paula Barros Terraciano
- Centro de Pesquisa Experimental, Laboratório de Bioquímica Farmacológica , Hospital de Clínicas de Porto Alegre (UFRGS) , Porto Alegre , RS 90035-007 , Brazil
| | - Alexandre R Campos
- Proteomics Core , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States
| | - Jorge A Guimarães
- Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia , Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , RS 90040-060 , Brazil.,Centro de Pesquisa Experimental, Laboratório de Bioquímica Farmacológica , Hospital de Clínicas de Porto Alegre (UFRGS) , Porto Alegre , RS 90035-007 , Brazil
| | - Marilene H Vainstein
- Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia , Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , RS 90040-060 , Brazil
| | - John R Yates
- Departments of Chemical Physiology and Molecular and Cellular Neuroscience , The Scripps Research Institute , La Jolla , California 92037 , United States
| | - Walter O Beys-da-Silva
- Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia , Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , RS 90040-060 , Brazil.,Centro de Pesquisa Experimental, Laboratório de Bioquímica Farmacológica , Hospital de Clínicas de Porto Alegre (UFRGS) , Porto Alegre , RS 90035-007 , Brazil.,Faculdade de Farmácia , Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , RS 90610-000 , Brazil
| |
Collapse
|
|
18
|
Grotto RMT, Santos FM, Picelli N, Silva GF, Ferrasi AC, Sarnighausen VCR, Pardini MIDMC. HPA-1a/1b could be considered a molecular predictor of poor prognosis in chronic hepatitis C. Rev Soc Bras Med Trop 2019; 52:e20170427. [PMID: 31271612 DOI: 10.1590/0037-8682-0427-2017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 03/21/2019] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION HPA polymorphism has been associated with HCV presence and fibrosis progression in chronic hepatitis C. However, it is unknown if there is an association between HPA-1 polymorphism and hepatocellular carcinoma (HCC). Therefore, this study aimed to evaluate HPA-1 polymorphism in the presence of HCC. METHODS PCR-SSP was used to perform HPA genotyping on 76 HCV-infected patients. RESULTS There was no association between patients with and without HCC. There was significant difference in HPA-1 genotypic frequency distribution between HCC and F1/F2 fibrosis degree. CONCLUSIONS The HPA-1a/1b polymorphism appears to be more associated with liver damage progression than with HCC presence.
Collapse
Affiliation(s)
- Rejane Maria Tommasini Grotto
- Laboratório de Biologia Molecular do Hemocentro, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil.,Universidade Estadual Paulista (UNESP), Faculdade de Ciências Agronômicas, Departamento de Bioprocessos e Biotecnologia, Botucatu, SP, Brasil
| | - Francielle Martins Santos
- Laboratório de Biologia Molecular do Hemocentro, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil
| | - Natália Picelli
- Laboratório de Biologia Molecular do Hemocentro, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil
| | - Giovanni Faria Silva
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | - Adriana Camargo Ferrasi
- Laboratório de Biologia Molecular do Hemocentro, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil.,Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | | | - Maria Inês de Moura Campos Pardini
- Laboratório de Biologia Molecular do Hemocentro, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil.,Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| |
Collapse
|
|
19
|
Li S, Xue F, Zheng Y, Yang P, Lin S, Deng Y, Xu P, Zhou L, Hao Q, Zhai Z, Wu Y, Dai Z, Chen S. GSTM1 and GSTT1 null genotype increase the risk of hepatocellular carcinoma: evidence based on 46 studies. Cancer Cell Int 2019; 19:76. [PMID: 30976200 PMCID: PMC6441207 DOI: 10.1186/s12935-019-0792-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Accepted: 03/20/2019] [Indexed: 02/06/2023] Open
Abstract
Background It is well known that hepatocellular carcinoma (HCC) has been one of the most life-threatening diseases all over the world. Plenty of internal and extrinsic factors have been proven to be related to HCC, such as gene mutation, viral hepatitis, and Nitrosamines. Though previous studies demonstrated that glutathione S-transferase (GST) genotypes are associated with HCC, the conclusions are inconsistent. Therefore, we carried on a renewed meta-analysis to expound the connection between the null GSTM1, GSTT1 polymorphisms and the risk of HCC. Methods We searched PubMed, Web of Science, Embase, and CNKI databases to select qualified researches which satisfied the inclusion criteria up to July 31, 2018. Finally, we selected 41 articles with 6124 cases and 9781 controls in this meta-analysis. We use ORs and 95% confidence interval (CI) to evaluate the correlation intension between the GSTM1 and GSTT1 null genes and the risk of HCC. All the statistical processes were executed by Stata (version 12.0). Results The pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18–1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23–1.66) increased the risk of HCC. And GSTM1–GSTT1 dual-null genotypes also increased the risk of HCC (OR = 1.58, 95% CI = 1.22–2.05). In the subgroup analysis, we obtained significant results among Asians when stratified by race, and the results are GSTM1 null OR = 1.44, 95% CI = (1.22–1.71), GSTT1 null OR = 1.48, 95% CI = (1.25–1.77), GSTM1–GSTT1 null OR = 1.58, 95% CI = (1.19–2.09), while we didn’t obtain significant results among Caucasians or Africans. Stratified analyses on the type of control indicated a higher risk of HCC associated with GSTM1, GSTT1 single null genotypes and GSTM1–GSTT1 dual-null genotypes in healthy people. No evidence of significant connection was discovered in chronic liver disease (CLD) except in GSTT1 single null. Conclusions Our study indicated that an individual who carries the GSTM1, GSTT1 single null genotypes and GSTT1–GSTM1 dual-null genotypes is more likely to develop HCC. Electronic supplementary material The online version of this article (10.1186/s12935-019-0792-3) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Shanli Li
- Department of Interventional Vascular Surgery, The Affiliated Bao ji Central Hospital of Xi'an Jiaotong University College of Medicine, Bao ji, 721008 Shaan xi China.,2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China
| | - Feng Xue
- 3Department of Hepatobiliary Surgery, The 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Tumor Hospital), Urumqi, 830000 China
| | - Yi Zheng
- 2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China
| | - Pengtao Yang
- 2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China
| | - Shuai Lin
- 2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China
| | - Yujiao Deng
- 2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China
| | - Peng Xu
- 2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China
| | - Linghui Zhou
- 2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China
| | - Qian Hao
- 2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China
| | - Zhen Zhai
- 2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China
| | - Ying Wu
- 2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China
| | - Zhijun Dai
- 2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China
| | - Shu Chen
- Department of Interventional Vascular Surgery, The Affiliated Bao ji Central Hospital of Xi'an Jiaotong University College of Medicine, Bao ji, 721008 Shaan xi China
| |
Collapse
|
|
20
|
Correia K, Williams PL. Estimating the Relative Excess Risk Due to Interaction in Clustered-Data Settings. Am J Epidemiol 2018; 187:2470-2480. [PMID: 30060004 PMCID: PMC6211249 DOI: 10.1093/aje/kwy154] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 07/19/2018] [Accepted: 07/20/2018] [Indexed: 01/01/2023] Open
Abstract
The risk difference scale is often of primary interest when evaluating public health impacts of interventions on binary outcomes. However, few investigators report findings in terms of additive interaction, probably because the models typically used for binary outcomes implicitly measure interaction on the multiplicative scale. One measure with which to assess additive interaction from multiplicative models is the relative excess risk due to interaction (RERI). The RERI measure has been applied in many contexts, but one limitation of previous approaches is that clustering in data has rarely been considered. We evaluated the RERI metric for the setting of clustered data using both population-averaged and cluster-conditional models. In simulation studies, we found that estimation and inference for the RERI using population-averaged models was straightforward. However, frequentist implementations of cluster-conditional models including random intercepts often failed to converge or produced degenerate variance estimates. We developed a Bayesian implementation of log binomial random-intercept models, which represents an attractive alternative for estimating the RERI in cluster-conditional models. We applied the methods to an observational study of adverse birth outcomes in mothers with human immunodeficiency virus, in which mothers were clustered within clinical research sites.
Collapse
Affiliation(s)
- Katharine Correia
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Paige L Williams
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| |
Collapse
|
|
21
|
Rezaei M, Saadat M. Association Between GSTP1 Ile105Val Genetic Polymorphism and Dependency to Heroin and Opium. Biochem Genet 2018; 57:214-221. [PMID: 30121884 DOI: 10.1007/s10528-018-9885-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 08/12/2018] [Indexed: 01/18/2023]
Abstract
Relationship between glutathione S-transferase P1 (GSTP1, OMIM: 134660) variants and the risk of drug dependency is unknown. Chronic use of illegal drugs leads to oxidative stress, which can be alleviated by cellular detoxification mechanisms. There are several polymorphisms in the GSTP1, including Ile105Val (rs1695). This polymorphism leads to an Ile105Val amino acid change and may alter the GSTP1 enzyme activity. There is no study on the association between this polymorphism and risks of heroin (HD) or opium (OD) dependency. This paper consists of two case-control studies. The first study consisted of 442 HD subjects and 794 healthy controls. The second study consisted of 143 cases with OD and 565 healthy blood donors as controls. Genotyping were carried out using PCR based method. The Ile/Val (OR 0.84, 95% CI 0.65-1.07, P = 0.165) and Val/Val (OR 0.87, 95% CI 0.56-1.36, P = 0.879) genotypes did not show significant association with the risk of HD. Neither the Ile/Val (OR 0.72, 95% CI 0.49-1.06, P = 0.103) nor the Val/Val (OR 0.61, 95% CI 0.29-1.30, P = 0.209) was associated with the risk of OD. The GSTP1 Ile105Val polymorphism was not associated with the risk of dependency to opium and heroin.
Collapse
Affiliation(s)
- Majede Rezaei
- Department of Biology, College of Sciences, Shiraz University, Shiraz, 71467-13565, Iran
| | - Mostafa Saadat
- Department of Biology, College of Sciences, Shiraz University, Shiraz, 71467-13565, Iran.
| |
Collapse
|
|
22
|
Kapahtia S, Hazam RK, Asim M, Karra VK, Chowdhury SJ, Das BC, Kar P. Role of Glutathione S Transferase M1 and T1 Gene Polymorphism in Hepatitis B Related Liver Diseases and Cryptogenic Cirrhosis. J Clin Exp Hepatol 2018; 8:169-172. [PMID: 29892180 PMCID: PMC5992258 DOI: 10.1016/j.jceh.2017.05.208] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2014] [Accepted: 05/24/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIM Progression of hepatitis B virus infection (HBV) might be affected by host genetic factors. The present study was undertaken to study the role of glutathione S-transferases (GST)-M1 and T1 gene polymorphisms in different stages of HBV infection: HBV inactive carrier, chronic hepatitis B and cirrhosis, and cryptogenic cirrhosis. METHODS The study population comprised of 170 subjects; 120 cases (HBV inactive carrier, n = 30; HBV related chronic hepatitis, n = 30; HBV related cirrhosis, n = 30; cryptogenic cirrhosis, n = 30) and 50 unrelated healthy adults without liver disease as controls. Analysis of GSTM1 and GSTT1 gene polymorphisms was done by multiplex polymerase chain reaction. RESULTS The GSTM1 null genotype was seen more commonly in hepatitis B cirrhosis (n = 21; 70%), chronic hepatitis B (n = 19; 63.33%) and cryptogenic cirrhosis (n = 17; 56.67%) as compared with inactive carrier (n = 9; 30%) and controls (n = 13; 26%). The GSTT1 null genotype was seen less frequently in all the groups, the observed frequencies were controls (n = 7; 14%), inactive carrier (n = 5; 16.67%), chronic hepatitis B (n = 8; 26.67%) and hepatitis B cirrhosis (n = 7; 23.33%). The difference of GSTM1 null genotype frequencies was statistically significant for hepatitis B cirrhosis vs. controls (P = 0.0002), chronic hepatitis B vs. controls (P = 0.002) and cryptogenic cirrhosis vs. controls (P = 0.01). The GSTT1 null genotype was not found to vary significantly between the groups. CONCLUSION The patients with GSTM1 null genotype are at risk of progression of liver disease as the frequency of GSTM1 null genotype was found to be significantly higher in chronic hepatitis B, hepatitis B cirrhosis and cryptogenic cirrhosis as compared with controls.
Collapse
Affiliation(s)
- Siddharth Kapahtia
- Department of Medicine, Maulana Azad Medical College, University of Delhi, India
| | - Rajib K. Hazam
- Department of Medicine, Maulana Azad Medical College, University of Delhi, India
| | - Mohammad Asim
- Department of Medicine, Maulana Azad Medical College, University of Delhi, India
| | - Vijay K. Karra
- Department of Medicine, Maulana Azad Medical College, University of Delhi, India
| | - Soumya J. Chowdhury
- Department of Medicine, Maulana Azad Medical College, University of Delhi, India
| | - Bhudev C. Das
- Dr B.R.Ambedkar Center for Biomedical Research, University of Delhi, India
| | - Premashis Kar
- Department of Medicine, Maulana Azad Medical College, University of Delhi, India,Address for correspondence: Premashis Kar, Department of Medicine, B.L.Taneja Block, R/N-127, New Delhi 110002, India. Tel.: +91 011 23230132; fax: +91 011 23230132.
| |
Collapse
|
|
23
|
Prysyazhnyuk VP, Rossokha ZI, Gorovenko NG. Variation in particular biochemical indicators, cytokine and adipokine profiles of the blood, and the structural and functional parameters of the liver in patients with nonalcoholic fatty liver disease and different genotypes by the polymorphic locus A313G of the GSTP1 gene. CYTOL GENET+ 2017. [DOI: 10.3103/s0095452717060111] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
|
|
24
|
De Mattia E, Cecchin E, Polesel J, Bignucolo A, Roncato R, Lupo F, Crovatto M, Buonadonna A, Tiribelli C, Toffoli G. Genetic biomarkers for hepatocellular cancer risk in a caucasian population. World J Gastroenterol 2017; 23:6674-6684. [PMID: 29085212 PMCID: PMC5643288 DOI: 10.3748/wjg.v23.i36.6674] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 05/17/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To uncover novel genetic markers that could contribute to predicting hepatocellular carcinoma (HCC) susceptibility in Caucasians.
METHODS The present retrospective case-control study compared genotype frequencies between a cohort of HCC cases and two, independent, HCC-free, age/sex-matched control groups. The HCC cohort comprised 192 homogeneous patients that had undergone orthotopic liver transplantation. The first control group comprised 167 patients that were matched to the HCC cohort for the percentage of hepatitis B (HBV) and/or hepatitis C (HCV) infections. A second control group included 192 virus-free, healthy individuals that were used to evaluate the generalizability of the identified predictive markers. All cases and controls were Caucasian. The three study populations were characterized with a panel of 31 markers derived from 21 genes that encoded key proteins involved in hepatocarcinogenesis-related pathways. The study end-point was to assess the association between genetic variants and HCC onset.
RESULTS Five genetic markers were identified as risk factors for HCC in high-risk patients infected with HBV/HCV. According to a dominant model, reduced HCC risk was associated with three polymorphisms: ERCC1 rs3212986 (OR = 0.46, 95%CI: 0.30-0.71, P = 0.0005), GST-P1 rs1138272 (OR = 0.41, 95%CI: 0.21-0.81, P = 0.0097), and CYP17A1 rs743572 (OR = 0.50, 95%CI: 0.31-0.79, P = 0.0032). Conversely, according to a recessive model, increased HCC risk was associated with two polymorphisms: XRCC3 rs1799794 (OR = 3.70, 95%CI: 1.02-13.39, P = 0.0461) and ABCB1 rs1128503 (OR = 2.06, 95%CI: 1.18-3.61, P = 0.0111). These associations remained significant in a subgroup analysis, where patients were stratified according to viral status (HBV- or HCV-positive serology). Two variants exhibited a serology-specific effect: ABCB1 rs1128503 (OR = 4.18, 95%CI: 1.55-11.29, P = 0.0048) showed an effect in the HBV-positive subgroup; and ERCC1 rs3212986 (OR = 0.33, 95%CI: 0.18-0.60, P = 0.0003) showed an effect in the HCV-positive subgroup. Among the five markers identified, ERCC1 rs3212986 (OR = 0.43, P < 0.0001) and CYP17A1 rs743572 (OR = 0.73, P = 0.0310) had a different distribution in patients with HCC compared to healthy individuals. With a recursive partitioning approach, we also demonstrated that significant gene-gene interactions between ERCC1 rs3212986, CYP17A1 rs743572, GST-P1 rs1138272, and the previously described UGT1A7*3 predictive marker, played a role in the complex trait of HCC susceptibility.
CONCLUSION We identified five polymorphisms and interactions that contributed crucially to predicting HCC risk. These findings represented an important step towards improving HCC diagnosis and management.
Collapse
Affiliation(s)
- Elena De Mattia
- Clinical and Experimental Pharmacology, “Centro di Riferimento Oncologico” - National Cancer Institute, 33081 Aviano, Italy
| | - Erika Cecchin
- Clinical and Experimental Pharmacology, “Centro di Riferimento Oncologico” - National Cancer Institute, 33081 Aviano, Italy
| | - Jerry Polesel
- Unit of Cancer Epidemiology, “Centro di Riferimento Oncologico” - National Cancer Institute, 33081 Aviano, Italy
| | - Alessia Bignucolo
- Clinical and Experimental Pharmacology, “Centro di Riferimento Oncologico” - National Cancer Institute, 33081 Aviano, Italy
| | - Rossana Roncato
- Clinical and Experimental Pharmacology, “Centro di Riferimento Oncologico” - National Cancer Institute, 33081 Aviano, Italy
| | - Francesco Lupo
- General Surgery 2U and Liver Transplantation Center, A.O.U. Città della Salute e della Scienza di Torino, University of Torino, 10124 Torino, Italy
| | - Marina Crovatto
- Cytogenetics and Molecular Biology Unit, Santa Maria degli Angeli Hospital Pordenone, 33170 Pordenone, Italy
| | - Angela Buonadonna
- Medical Oncology Unit, “Centro di Riferimento Oncologico” - National Cancer Institute, 33081 Aviano, Italy
| | | | - Giuseppe Toffoli
- Clinical and Experimental Pharmacology, “Centro di Riferimento Oncologico” - National Cancer Institute, 33081 Aviano, Italy
| |
Collapse
|
|
25
|
GSTP1 and XRCC1 polymorphisms and DNA damage in agricultural workers exposed to pesticides. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2017. [DOI: 10.1016/j.mrgentox.2017.05.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
|
|
26
|
Wang W, Liu F, Wang C, Wang C, Tang Y, Jiang Z. Glutathione S-transferase A1 mediates nicotine-induced lung cancer cell metastasis by promoting epithelial-mesenchymal transition. Exp Ther Med 2017; 14:1783-1788. [PMID: 28810650 DOI: 10.3892/etm.2017.4663] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Accepted: 03/31/2017] [Indexed: 12/22/2022] Open
Abstract
The present study aimed to investigate the effect of glutathione S-transferase A1 (GSTA1) on lung cancer cell viability, invasion and adhesion in the presence of nicotine in vitro. Furthermore, the effect of GSTA1 on the epithelial-mesenchymal transition (EMT), a process strongly associated with lung cancer metastasis, was examined. Human lung carcinoma A549 cells were treated with various concentrations of nicotine (0.01, 0.1, 1 and 10 µM) and levels of GSTA1 mRNA and protein were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. To knock down GSTA1 expression, GSTA1-small interfering RNA was transfected into A549 cells. Cell viability, invasion and adhesion abilities were determined by MTT, Transwell-Matrigel invasion and cell adhesion assays, respectively. The expression of the epithelial cell markers E-cadherin and keratin, and the mesenchymal cell markers vimentin and N-cadherin in A549 cells were examined by western blot analysis. The current study indicated that the expression of GSTA1 was increased in A549 cells following nicotine treatment. GSTA1 suppression inhibited the viability, invasion and adhesion of lung cancer cells. In addition, the increase in lung cancer cell viability, invasion and adhesion by nicotine was suppressed following GSTA1 knockdown. Furthermore, GSTA1 affected the expression of EMT markers in nicotine-treated or untreated lung cancer cells. Thus the present study demonstrates that GSTA1 promotes lung cancer cell invasion and adhesion and mediates the effect of nicotine on lung cancer cell metastasis in vitro. Furthermore, the results demonstrated that GSTA1 exerts its effect on lung cancer cell metastasis by promoting the EMT.
Collapse
Affiliation(s)
- Wei Wang
- Department of Thoracic Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China.,Department of Thoracic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Feiyu Liu
- Department of Pharmacy, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China
| | - Chaoyang Wang
- Department of Thoracic Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China
| | - Chengde Wang
- Department of Thoracic Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China
| | - Yijun Tang
- Department of Thoracic Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China
| | - Zhongmin Jiang
- Department of Thoracic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| |
Collapse
|
|
27
|
Abstract
There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.
Collapse
|
|
28
|
Walesky C, Goessling W. Nature and nurture: Environmental toxins and biliary atresia. Hepatology 2016; 64:717-9. [PMID: 27349921 DOI: 10.1002/hep.28701] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 06/14/2016] [Indexed: 12/30/2022]
Affiliation(s)
- Chad Walesky
- Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Wolfram Goessling
- Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.,Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.,Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, MA.,Broad Institute of MIT and Harvard, Cambridge, MA.,Harvard Stem Cell Institute, Cambridge, MA
| |
Collapse
|
|
29
|
Toyoda Y, Takada T, Suzuki H. Halogenated hydrocarbon solvent-related cholangiocarcinoma risk: biliary excretion of glutathione conjugates of 1,2-dichloropropane evidenced by untargeted metabolomics analysis. Sci Rep 2016; 6:24586. [PMID: 27087417 PMCID: PMC5263858 DOI: 10.1038/srep24586] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Accepted: 03/30/2016] [Indexed: 12/15/2022] Open
Abstract
Recently, the International Agency for Research on Cancer issued a warning about the carcinogenicity of 1,2-dichloropropane (1,2-DCP) to humans based on an epidemiological study suggesting a relationship between the incidence of cholangiocarcinoma and occupational exposure to halogenated hydrocarbon solvent comprised mostly of 1,2-DCP. Although this dihaloalkane has been used in various industrial fields, there has been no biological evidence explaining the cholangiocarcinoma latency, as well as little understanding of general cholangiocarcinoma risk. In the present study, we explored the biliary excretion of 1,2-DCP metabolites by an untargeted metabolomics approach and the related molecular mechanism with in vitro and in vivo experiments. We hypothesized that the biliary excretion of carcinogens derived from 1,2-DCP contribute to the increased cholangiocarcinoma risk. We found that 1,2-DCP was conjugated with glutathione in the liver, and that the glutathione-conjugated forms of 1,2-DCP, including a potential carcinogen that contains a chloride atom, were excreted into bile by the bile canalicular membrane transporter, ABCC2. These results may reflect a risk in the backfiring of biliary excretion as a connatural detoxification systems for xenobiotics. Our findings would contribute to uncover the latent mechanism by which the chronic exposure to 1,2-DCP increases cholangiocarcinoma risk and future understanding of cholangiocarcinoma biology.
Collapse
Affiliation(s)
- Yu Toyoda
- Department of Pharmacy, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Tappei Takada
- Department of Pharmacy, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Hiroshi Suzuki
- Department of Pharmacy, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| |
Collapse
|
|
30
|
Wu B, Jiang Y, Zhu F, Sun D, Huang H. Demethylation effects of elemene on the GSTP1 gene in HCC cell line QGY7703. Oncol Lett 2016; 11:2545-2551. [PMID: 27073515 DOI: 10.3892/ol.2016.4243] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Accepted: 01/21/2015] [Indexed: 12/13/2022] Open
Abstract
The present study aimed to investigate elemene's effects on cell proliferation, apoptosis, and the cell cycle in the hepatocellular carcinoma (HCC) cell line, QYG7703, and to investigate GSTP1 gene methylation change in QGY7703 cells after being treated with elemene to explore whether elemene reversed the abnormal GSTP1 gene methylation. QGY7703 cells were treated with different elemene concentrations. Cell proliferation was measured with MTT assay, cell apoptosis and cell cycle were analyzed by flow cytometry, and GSTP1 gene methylation was analyzed by methlation-specific polymerase chain reaction. The cells' apoptotic rate increased dose-dependently with elemene concentration, and the difference was statistically significant (P<0.05). Elemene treatment arrested the cells in S phase, and thus the percentage of cells in G1 phase decreased while the cells in S phase increased dose-dependently, and the difference was statistically significant compared to the control group (P<0.05). All QGY7703 cells were identified to contain GSTP1 gene methylation before being treated with elemene and the methylation state decreased after treatment. In the present study, elemene induced cell apoptosis, inhibited the cell cycle, and reversed GSTP1 gene methylation in QGY7703 cells.
Collapse
Affiliation(s)
- Baoqiang Wu
- Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, Changzhou 213003, P.R. China
| | - Yong Jiang
- Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, Changzhou 213003, P.R. China
| | - Feng Zhu
- Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, Changzhou 213003, P.R. China
| | - Donglin Sun
- Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, Changzhou 213003, P.R. China
| | - Hongjun Huang
- Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, Changzhou 213003, P.R. China
| |
Collapse
|
|
31
|
WU MUYUN, HUANG SHUJING, LIU DONG, PENG MIAO, YANG FAN, WANG XICHENG. Association of the p53 or GSTM1 polymorphism with the risk of nasopharyngeal carcinoma: A meta-analysis. Mol Clin Oncol 2016; 4:221-228. [PMID: 26893866 PMCID: PMC4734025 DOI: 10.3892/mco.2015.700] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 11/12/2015] [Indexed: 12/08/2022] Open
Abstract
p53 and glutathione S-transferase M1 (GSTM1) are the most popular suppressor genes. Several previous studies demonstrated positive associations of these gene polymorphisms with numerous cancer types, including hepatocellular cancer, while the association between p53/GSTM1 polymorphisms and the nasopharyngeal carcinoma (NPC) risk was inconsistent and underpowered. However, no studies investigating the combinational effect of these two genes on NPC risk were performed. To confirm the effects of p53 and GSTM1 polymorphisms on the risk of NPC, a meta-analysis of all the available previous studies associating p53 and GSTM1 with the risk of NPC was performed. A comprehensive search of PubMed, Web of Science and SD database until November 2014 was performed to identify the relevant studies. The data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. Finally, five studies with 1,419 cases and 1,707 controls were included for the p53 polymorphism and three studies with 837 cases and 1,299 controls were included for the GSTM1 polymorphism. Regarding p53, a significantly increased NPC risk was observed in the overall population (C vs. G, OR, 1.245; 95% CI, 1.045-1.483; P=0.014; additive models: CC vs. GG, OR, 1.579; 95% CI, 1.100-2.265; P=0.013 and CG vs. GG, OR, 1.230; 95% CI, 1.039-1.456; P=0.016; dominant model, OR, 1.321; 95% CI, 1.127-1.549; P=0.001; recessive model, OR, 1.429; 95% CI, 1.017-2.009; P=0.040). Concerning GSTM1, a significantly increased NPC risk was observed in the overall population (null versus non-null, OR, 1.282; 95% CI, 1.075-1.530; P=0.006). In the subgroup analyses stratified by the source of controls, a significant association of p53 with NPC risk was also demonstrated, while no association with GSTM1 was observed. Therefore, the p53 G72C polymorphism may have a susceptible role in the carcinogenesis of NPC, while genetic deletion of GSTM1 may contribute to increased susceptibility to NPC. Further large and well-designed studies are required to confirm this association.
Collapse
Affiliation(s)
- MUYUN WU
- Department of Oncology, The Fifth People's Hospital of Wuhu, Wuhu, Anhui 241000, P.R. China
| | - SHUJING HUANG
- Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China
| | - DONG LIU
- Department of Internal Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China
| | - MIAO PENG
- Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China
| | - FAN YANG
- Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China
| | - XICHENG WANG
- Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China
- Correspondence to: Mr. Xicheng Wang, Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China, E-mail:
| |
Collapse
|
|
32
|
Wang Z, Qu K, Niu W, Lin T, Xu X, Huang Z, Liu S, Liu S, Chang H, Liu Y, Dong X, Liu C, Zhang Y. Glutathione S-transferase P1 gene rs4147581 polymorphism predicts overall survival of patients with hepatocellular carcinoma: evidence from an enlarged study. Tumour Biol 2015; 37:943-52. [PMID: 26260272 DOI: 10.1007/s13277-015-3871-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2015] [Accepted: 07/30/2015] [Indexed: 02/07/2023] Open
Abstract
As the most important detoxifying enzymes in liver, glutathione S-transferases (GSTs) can protect hepatocytes against carcinogens. We conducted a large cohort study to investigate the prognostic value of single nucleotide polymorphisms (SNPs) in seven encoding genes of GSTs for hepatocellular carcinoma (HCC). Twelve SNPs were genotyped and correlated with overall survival in 469 HCC patients. The median follow-up time of all patients was 21 (range 3-60) months, and the median survival time was 22 months. By the end of the study, 135 (28.8 %) patients were alive. Only rs4147581 in GSTP1 gene exhibited a significant association with survival of HCC patients (P = 0.006), with its mutant allele bearing a significantly lower risk of death (hazard ratio, 0.71; 95 % confidence interval 0.53-0.90), compared with the homozygous wide-type. A longer median survival time in patients with rs4147581 mutant allele was noticed than those homozygous wide-type (P = 0.03), and there was a marked adverse effect on survival conferred by smoking exposure in these patients. Conclusively, our findings provide supporting evidence for a contributory role of GSTP1 rs4147581 polymorphism in predicting the prognosis of HCC.
Collapse
Affiliation(s)
- Zhixin Wang
- Department of Imaging, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China.,Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Kai Qu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Wenquan Niu
- State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin Second Road 197, New Huangpu District, Shanghai, 200025, China.
| | - Ting Lin
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Xinsen Xu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Zichao Huang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Sushun Liu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Sinan Liu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Hulin Chang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Yamin Liu
- Department of Cardiology and Periphery Vascular Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Xiaoqun Dong
- Department of Internal Medicine, College of Medicine, The University of Oklahoma Health Sciences Center, 975 NE 10th Street, Biomedical Research Center BRC1366, Oklahoma, OK, 73104, USA.
| | - Chang Liu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Yuelang Zhang
- Department of Imaging, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China.
| |
Collapse
|
|
33
|
Qu K, Liu SS, Wang ZX, Huang ZC, Liu SN, Chang HL, Xu XS, Lin T, Dong YF, Liu C. Polymorphisms of glutathione S-transferase genes and survival of resected hepatocellular carcinoma patients. World J Gastroenterol 2015; 21:4310-4322. [PMID: 25892883 PMCID: PMC4394094 DOI: 10.3748/wjg.v21.i14.4310] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 08/19/2014] [Accepted: 10/21/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of single nucleotide polymorphisms (SNPs) in glutathione S-transferase (GST) genes on survival of hepatocellular carcinoma (HCC) patients.
METHODS: Twelve tagging SNPs in GST genes (including GSTA1, GSTA4, GSTM2, GSTM3, GSTO1, GSTO2 and GSTP1) were genotyped using Sequenom MassARRAY iPLEX genotyping method in a cohort of 214 Chinese patients with resected HCC. The Cox proportional hazards model and log-rank test were performed to determine the SNPs related to outcome. Additionally, stratified analysis was performed at each level of the demographic and clinical variables. An SNP-gene expression association model was further established to investigate the correlation between SNP and gene expression.
RESULTS: Two SNPs (GSTO2: rs7085725 and GSTP1: rs4147581) were significantly associated with overall survival in HCC patients (P = 0.035 and 0.042, respectively). In stratified analysis, they were more significantly associated with overall survival in patients with younger age, male gender and cirrhosis. We further investigated cumulative effects of these two SNPs on overall survival in HCC patients. Compared with the patients carrying no unfavorable genotypes, those carrying 2 unfavorable genotypes had a 1.70-fold increased risk of death (P < 0.001). The cumulative effects were more significant in those patients with younger age, male gender and cirrhosis (HR = 2.00, 1.94 and 1.97, respectively; all P < 0.001). Additionally, we found that heavy smoking resulted in a significantly worse overall survival in those patients carrying variant alleles of rs7085725 (HR = 2.07, 95%CI: 1.13-3.76, P = 0.018). The distributions of GSTO2: rs7085725 and GSTP1: rs4147581 genotypes were associated with altered gene expression and contributed to influences on overall survival.
CONCLUSION: Our study provides the first evidence that GSTO2 and GSTP1 gene polymorphisms may serve as independent prognostic markers for HCC patients.
Collapse
|
|
34
|
Så RAD, Moreira ADS, Cabello PH, Ornellas AA, Costa EB, Matos CDS, Alves G, Hatagima A. Human glutathione S-transferase polymorphisms associated with prostate cancer in the Brazilian population. Int Braz J Urol 2015; 40:463-73. [PMID: 25251951 DOI: 10.1590/s1677-5538.ibju.2014.04.04] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Accepted: 03/22/2014] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE To evaluate the influence of polymorphisms in GSTA1, GSTM1, GSTT1, and GSTP1 in the risk of developing Prostate Cancer (PCa) in a population of Rio de Janeiro and compare the distribution of allele and genotype frequencies of the polymorphisms analyzed in the present study population with other regions in the country and different ethnic groups. MATERIALS AND METHODS We analyzed a sample of the Brazilian population, comprising 196 patients with PCa treated by the urology services of the Brazilian National Cancer Institute (INCA) and Mario Kroeff Hospital (HMK), and 208 male blood donors from the Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro (UFRJ). The polymorphisms were determined in DNA, extracted from peripheral blood leucocytes using the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS Our results showed that the distribution of polymorphisms can vary significantly according to the Brazilian region and ethnic groups. The distribution of allele and genotype frequencies of the polymorphism GSTA1 was statistically different between cases and controls. Genotypes (A / B + B / B) were associated with protection (OR = 0.61, 95% CI = 0.40-0.92) for PCa in comparison to genotype A / A. CONCLUSION The distribution of genotype frequencies of the polymorphism GSTA1 was statistically different between the case and control groups (p = 0.023), and the presence of genotypes A / B and B / B suggests a protective role against the risk of PCa compared to genotype A / A. This is the first study that reports the genotypic frequency of this polymorphism and its association with PCa in a Brazilian population sample.
Collapse
Affiliation(s)
- Renata Almeida de Så
- Laboratory of Human Genetics and Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute / Oswaldo Cruz Foundation; Laboratory of Applied Genetics, Hematology Service, Rio de Janeiro, RJ, Brazil
| | - Aline Dos Santos Moreira
- Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute / Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil
| | - Pedro Hernan Cabello
- Laboratory of Human Genetics Oswaldo Cruz Institute / Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil and Brazilian National Institute of Cancer; Laboratory of Human Genetics, Grande Rio University (UNIGRANRIO), Rio de Janeiro, RJ, Brazil
| | - Antonio Augusto Ornellas
- Urology Service of Brazilian National Institute of Cancer, Rio de Janeiro, RJ, Brazil and Mário Kroeff Hospital, Rio de Janeiro, RJ, Brazil
| | - Eduardo Butinhão Costa
- Laboratory of Human Genetics, Oswaldo Cruz Institute / Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil
| | - Cintia da Silva Matos
- Laboratory of Applied Genetics, Hematology Service Brazilian National Institute of Cancer, Rio de Janeiro, RJ, Brazil and Laboratory of Clinical Pathology, Brazilian National Institute of Cancer, Rio de Janeiro, RJ, Brazil
| | - Gilda Alves
- Laboratory of Applied Genetics, Hematology Service Brazilian National Institute of Cancer, Rio de Janeiro, RJ, Brazil
| | - Ana Hatagima
- Laboratory of Human Genetics, Oswaldo Cruz Institute / Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil
| |
Collapse
|
|
35
|
Eroğlu P, Erkol İnal E, Sağ ŞÖ, Görükmez Ö, Topak A, Yakut T. Associations analysis of GSTM1, T1 and P1 Ile105Val polymorphisms with carpal tunnel syndrome. Clin Rheumatol 2015; 35:1245-51. [DOI: 10.1007/s10067-014-2855-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2014] [Revised: 12/14/2014] [Accepted: 12/16/2014] [Indexed: 12/20/2022]
|
|
36
|
Bosetti C, Turati F, La Vecchia C. Hepatocellular carcinoma epidemiology. Best Pract Res Clin Gastroenterol 2014; 28:753-70. [PMID: 25260306 DOI: 10.1016/j.bpg.2014.08.007] [Citation(s) in RCA: 386] [Impact Index Per Article: 35.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Accepted: 08/15/2014] [Indexed: 01/31/2023]
Abstract
Primary liver cancer (namely hepatocellular carcinoma, HCC) is worldwide the fifth most common cancer in men and the seventh one in women, and it represents the third most frequent cause of cancer death. HCC rates are particularly high in eastern/south-eastern Asia and in Africa, intermediate in Southern Europe, and low in most high-income countries. Persistent infections by HBV or HCV are the main recognized risk factors for HCC. Aflatoxin exposure is also an important risk factor for HCC development in Africa and eastern Asia. In high-income countries heavy alcohol drinking, tobacco smoking, overweight, diabetes, familial/genetic factors, and selected dietary aspects, have a relevant role. Updated geographic patterns and time trends in mortality from HCC in Europe, USA, Japan, and Australia are provided in the present review, together with an overview of relevant etiologic factors for HCC and main measures for the prevention of this neoplasm.
Collapse
Affiliation(s)
- Cristina Bosetti
- Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Via G. La Masa 19, 20156 Milan, Italy.
| | - Federica Turati
- Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Via G. La Masa 19, 20156 Milan, Italy.
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via A. Vanzetti 5, 20133 Milan, Italy.
| |
Collapse
|
|
37
|
Functional compensation of glutathione S-transferase M1 (GSTM1) null by another GST superfamily member, GSTM2. Sci Rep 2014; 3:2704. [PMID: 24048194 PMCID: PMC3776957 DOI: 10.1038/srep02704] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Accepted: 08/06/2013] [Indexed: 11/08/2022] Open
Abstract
The gene for glutathione-S-transferase (GST) M1 (GSTM1), a member of the GST-superfamily, is widely studied in cancer risk with regard to the homozygous deletion of the gene (GSTM1 null), leading to a lack of corresponding enzymatic activity. Many of these studies have reported inconsistent findings regarding its association with cancer risk. Therefore, we employed in silico, in vitro, and in vivo approaches to investigate whether the absence of a functional GSTM1 enzyme in a null variant can be compensated for by other family members. Through the in silico approach, we identified maximum structural homology between GSTM1 and GSTM2. Total plasma GST enzymatic activity was similar in recruited individuals, irrespective of their GSTM1 genotype (positive/null). Furthermore, expression profiling using real-time PCR, western blotting, and GSTM2 overexpression following transient knockdown of GSTM1 in HeLa cells confirmed that the absence of GSTM1 activity can be compensated for by the overexpression of GSTM2.
Collapse
|
|
38
|
GSTM1 null polymorphisms is associated with laryngeal cancer risk: a meta-analysis. Tumour Biol 2014; 35:6303-9. [DOI: 10.1007/s13277-014-1828-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Accepted: 03/05/2014] [Indexed: 11/26/2022] Open
|
|
39
|
Chiang CC, Lin CL, Peng CL, Sung FC, Tsai YY. Increased risk of cancer in patients with early-onset cataracts: a nationwide population-based study. Cancer Sci 2014; 105:431-6. [PMID: 24450445 PMCID: PMC4317801 DOI: 10.1111/cas.12360] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2013] [Revised: 01/17/2014] [Accepted: 01/18/2014] [Indexed: 01/16/2023] Open
Abstract
Early-onset cataracts are associated with insufficient antioxidative activity, and, therefore, a potential risk of cancer. This study investigated the risk of cancer after being diagnosed with early-onset cataracts. Retrospective claims data from the Taiwan National Health Insurance Research Database were analyzed. Study subjects were comprised of patients with early-onset cataracts, aged 20–55 years (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 366.00, 366.01, 366.02, 366.03, 366.04, 366.09, 366.17 and 366.18) and newly diagnosed between 1997 and 2010 (n = 1281), and a comparison cohort without the disease (n = 5124). Both cohorts were followed up until 2010 to estimate the incidences of cancer. We used the Poisson regression model to compare incidence rate ratios and the 95% confidence interval (CI). Cox proportional hazards regression was used to assess the hazard ratio (HR) of cancer associated with early-onset cataracts. The overall incidence rate of all cancers was 2.19-fold higher in the early-onset cataract cohort than in the comparison cohort (8.06 vs 3.68 per 1000 person-years) with an adjusted HR of 2.13 (95% CI = 1.48, 3.07). The site-specific analysis also showed a strong relationship, with adjusted HR of 3.24 ((95% CI = 1.30, 8.10) for head and neck cancer, 3.29 (95% CI 1.16, 9.31) for hepatoma and 3.19 (95% CI 1.34, 7.58) for breast cancer. The present study suggests that patients with early-onset cataracts are at an increased risk of being diagnosed with cancer in subsequent years.
Collapse
Affiliation(s)
- Chun Chi Chiang
- Division of Ophthalmology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University College of Medicine, Taichung, Taiwan
| | | | | | | | | |
Collapse
|
|
40
|
Yamada I, Matsuyama M, Ozaka M, Inoue D, Muramatsu Y, Ishii H, Junko U, Ueno M, Egawa N, Nakao H, Mori M, Matsuo K, Nishiyama T, Ohkawa S, Hosono S, Wakai K, Nakamura K, Tamakoshi A, Kuruma S, Nojima M, Takahashi M, Shimada K, Yagyu K, Kikuchi S, Lin Y. Lack of Associations between Genetic Polymorphisms in GSTM1, GSTT1 and GSTP1 and Pancreatic Cancer Risk: A Multi-Institutional Case-Control Study in Japan. Asian Pac J Cancer Prev 2014; 15:391-5. [DOI: 10.7314/apjcp.2014.15.1.391] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
|
|
41
|
Al-Husseini W, Gondro C, Quinn K, Herd RM, Gibson JP, Chen Y. Expression of candidate genes for residual feed intake in Angus cattle. Anim Genet 2013; 45:12-9. [PMID: 24134470 DOI: 10.1111/age.12092] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/20/2013] [Indexed: 11/30/2022]
Abstract
Residual feed intake (RFI) has been adopted in Australia for the purpose of genetic improvement in feed efficiency in beef cattle. RFI is the difference between the observed feed intake of an animal and the predicted feed intake based on its size and growth rate over a test period. Gene expression of eight candidate genes (AHSG, GHR, GSTM1, INHBA, PCDH19, S100A10, SERPINI2 and SOD3), previously identified as differentially expressed between divergent lines of high- and low-RFI animals, was measured in an unselected population of 60 steers from the Angus Society Elite Progeny Test Program using quantitative real-time PCR. Results showed that the levels of gene expression were significantly correlated with RFI. The genes explain around 33.2% of the phenotypic variance in RFI, and prediction equations using the expression data are reasonably accurate estimators of RFI. The association of these genes with economically important traits, such as other feed efficiency-related traits and fat, growth and carcass traits, was investigated as well. The expression of these candidate genes was significantly correlated with feed conversion ratio and daily feed intake, which are highly associated with RFI, suggesting a functional role for these genes in modulating feed utilisation. The expression of these genes did not show any association with average daily gain, eye muscle area and carcass composition.
Collapse
Affiliation(s)
- W Al-Husseini
- Australian Cooperative Research Centre for Beef Genetic Technologies, University of New England, Armidale, NSW, Australia; The Centre for Genetic Analysis and Applications, University of New England, Armidale, NSW, 2351, Australia
| | | | | | | | | | | |
Collapse
|
|
42
|
Abstract
Our understanding of the patho-physiology of hepatocellular carcinoma (HCC) is still much fragmented making difficult the improvement of the clinical outcome for the majority of HCC patients. Discovery of single nucleotide polymorphisms (SNPs) associated with individual susceptibility to HCC may enable the persons at risk to adapt their lifestyle and legitimate implementation by their doctors of surveillance programs facilitating early detection and subsequent management of the disease. To shed light on the influence of human genetic variation on HCC, we conducted a review of the meta-analyses of candidate SNPs and genome wide association studies (GWAS) performed for HCC by search of PubMed and Google Scholar databases. Genetic variations occurring in pathways historically considered as instrumental for liver tumorigenesis (TP53/MDM2, HLA, glutathione-S-transferases/cytochrome P540, TNFα/TGFβ, etc…) are discussed. An immense majority of the data has been produced in Eastern Asia (China, Japan, Korea). These meta-analyses indicate that the TP53, the MDM2 SNP309 G and the GSTT1 null genotype contribute to an increased risk of HCC both in Asians and Caucasians. Significant differences of odds ratios are, however, commonly observed between Eastern-Asians and other populations. Amazingly, GWAS studies performed so far exclusively with HCC patients from Eastern Asia produced drastically different outcomes pointing at unrelated biological pathways. The small magnitude of the risk associated with the genetic variants raises the question of their future utility as markers in clinical practice. An assessment of their impact on tumor progression (vascular invasion, metastases) remains, however, to be done and may prove to be more useful for clinicians. Finally, the evaluation of these variants is not available for various populations of the world and particularly for Subsaharan Africans who are especially affected by HCC.
Collapse
Affiliation(s)
- Sayeh Ezzikouri
- Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco. .,Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc 1, Place Louis Pasteur, 20360, Casablanca, Morocco.
| | - Soumaya Benjelloun
- Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco
| | - Pascal Pineau
- Unité Organisation Nucléaire et Oncogenèse, INSERM U993, Institut Pasteur, Paris, France
| |
Collapse
|
|
43
|
Abstract
Hepatocellular carcinoma (HCC) is increasing in incidence and has a very high fatality rate. Cirrhosis due to chronic hepatitis B or hepatitis C is the leading risk factor for HCC. Global epidemiology of HCC is determined by the prevalence of dominant viral hepatitis and the age it is acquired in the underlying population. Upcoming risk factors include obesity, diabetes, and related nonalcoholic fatty liver disease. This review discusses the latest trends of HCC globally and in the United States. It also provides an evidence-based commentary on the risk factors and lists some of the preventive measures to reduce the incidence of HCC.
Collapse
|
|
44
|
Ge J, Tian AX, Wang QS, Kong PZ, Yu Y, Li XQ, Cao XC, Feng YM. The GSTP1 105Val allele increases breast cancer risk and aggressiveness but enhances response to cyclophosphamide chemotherapy in North China. PLoS One 2013; 8:e67589. [PMID: 23826324 PMCID: PMC3691318 DOI: 10.1371/journal.pone.0067589] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Accepted: 05/20/2013] [Indexed: 12/22/2022] Open
Abstract
The glutathione-S-transferase (GST) family contributes to the inactivation of various toxic compounds formed as secondary metabolites during oxidative stress. GSTP1 accounts for the majority of the GST family enzymatic activity, and the activity of GSTP1 enzyme can be altered by the presence of the Ile105Val polymorphism. In this study, we examined the polymorphic frequency of GSTP1 Ile105Val genotype in 920 breast cancer patients and 783 healthy controls in women of North China. Results showed that GSTP1 105Val allele (Ile/Val and Val/Val) was associated with a higher breast cancer risk (OR = 1.38, 95% CI: 1.14–1.69; P = 0.001) and more aggressive tumors with histological grade III (OR = 1.15, 95% CI: 1.05–1.26; P = 0.001), lymph node metastases (OR = 2.35, 95% CI: 1.72–3.21; P < 0.001), as well as ER negative (OR = 1.77, 95% CI: 1.31–2.39; P < 0.001) than those carrying the Ile/Ile allele. However, the patients with the GSTP1 105Val genotype had a better disease free survival after cyclophosphamide (CTX)-based chemotherapy than those with Ile/Ile (HR = 0.77, 95% CI: 0.45–0.91; P < 0.001). Furthermore, in vitro cellular experiments demonstrated that breast cancer cells with the GSTP1 105Val allele were significantly more sensitive to CTX-induced proliferation inhibition. Thus, we conclude that the GSTP1 105Val allele increases breast cancer risk and aggressiveness and enhance response to CTX-based chemotherapy in women of North China. Detection of the GSTP1 Ile105Val genotype may help screen for high-risk populations and direct individualized therapy.
Collapse
Affiliation(s)
- Jie Ge
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Department of Breast surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Ai-Xian Tian
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Qing-Shan Wang
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Peng-Zhou Kong
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yue Yu
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Xiao-Qing Li
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Xu-Chen Cao
- Department of Breast surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yu-Mei Feng
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- * E-mail:
| |
Collapse
|
|
45
|
Zhao Y, Wang Q, Deng X, Shi P, Wang Z. Quantitative assessment of the association between GSTP1 gene Ile105Val polymorphism and susceptibility to hepatocellular carcinoma. Tumour Biol 2013; 34:2121-6. [DOI: 10.1007/s13277-013-0695-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Accepted: 02/03/2013] [Indexed: 12/25/2022] Open
|
|
46
|
Chen J, Ma L, Peng NF, Wang SJ, Li LQ. Relationship between GSTT1 gene polymorphism and hepatocellular carcinoma in patients from China. Asian Pac J Cancer Prev 2013; 13:4417-21. [PMID: 23167353 DOI: 10.7314/apjcp.2012.13.9.4417] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE The results from studies on associations of the glutathione S-transferase T1 (GSTT1) gene polymorphism and hepatocellular carcinoma (HCC) risk in Chinese populations are still conflicting. This meta- analysis was performed to evaluate the relationship in detail. METHODS Eligible reports were recruited into this meta-analysis from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database). Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. RESULTS Eighteen investigations were identified for the analysis of association between polymorphic deletion of GSTT1 and HCC, consisting of 2,693 patients with HCC and 4,696 controls. Null genotype of GSTT1 was associated with HCC susceptibility in Chinese (OR=1.53, 95%CI: 1.28-1.82; P<0.00001). CONCLUSION The GSTT1 null genotype is associated with HCC susceptibility in Chinese.
Collapse
Affiliation(s)
- Jie Chen
- Department of Hepatobiliary Surgery, The Tumor Affiliated Hospital of Guangxi Medical University, Nanning, China
| | | | | | | | | |
Collapse
|
|
47
|
Li CG, Zhao ZM, Hu MG, Liu R. Predictive role of glutathione-S-transferase gene polymorphisms in risk and prognosis of hepatocellular carcinoma. Asian Pac J Cancer Prev 2013; 13:3247-52. [PMID: 22994742 DOI: 10.7314/apjcp.2012.13.7.3247] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
AIM We conducted a prospective study in an Chinese population to detect associations of GSTM, GSTT and GSTP polymorphisms with hepatocellular carcinoma (HCC), and analyze roles in determining survival outcome. METHODS A prospective follow-up study was conducted with 476 HCC patients and 481 controls collected from May 2005 to May 2007. All patients were followed up until the end of Dec. 2011. GSTM1, GSTT1 and GSTP1 genotyping were performed by PCR-CTPP methods. RESULTS Null GSTM1 carriers had a 1.64 fold risk of HCC compared with non-null genotype, while GSTP1 Val/Val carriers had a 93% increased risk over the GSTP1 IIe/IIe genotype. The median follow-up time for the 476 patients was 34.2 months (range: 1 to 78 months). Individuals with null GSTM1 genotype had better survival of HCC than non-null genotype carriers (HR=0.71, 95%CI=0.45-0.95). Similarly, GSTP1 Val/Val genotypes had significant better survival than the GSTP1 IIe/IIe genotype (HR=0.34, 95%CI=0.18-0.65). Individuals carrying null GSTM1 and GSTP1 Val/Val who received chemotherapy had lower risk of death from HCC than those without chemotherapy. CONCLUSION This study indicated carriage of null GSTM1 and GSTP1 Val/Val genotypes to have roles in susceptibility to and survival from HCC.
Collapse
Affiliation(s)
- Cheng-Gang Li
- Department of Surgical Oncology, Chinese PLA General Hospital, Beijing, China
| | | | | | | |
Collapse
|
|
48
|
Murthy AK, Kumar V, Suresh K. Meta-analysis of GSTM1 and GSTT1 Polymorphisms and Risk of Nasopharyngeal Cancer. Asian Pac J Cancer Prev 2013; 14:1697-701. [DOI: 10.7314/apjcp.2013.14.3.1697] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
|
|
49
|
Qi L, Zou ZQ, Wang LY, Gao S, Fan YC, Long B, Guo YM, Xu AL, Han J, Li T, Wang K. Methylation of the glutathione-S-transferase M3 gene promoter is associated with oxidative stress in acute-on-chronic hepatitis B liver failure. TOHOKU J EXP MED 2013; 228:43-51. [PMID: 22976281 DOI: 10.1620/tjem.228.43] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Chronic hepatitis B (CHB) is a major cause for liver disease worldwide, ranking as the first cause for liver cirrhosis and hepatocellular carcinoma. Acute-on-chronic hepatitis B liver failure (ACHBLF) is most commonly caused by acute severe exacerbation during CHB virus infection. The pathophysiology of ACHBLF is still poorly understood. Glutathione-S-transferase (GST) M3 belongs to GSTs superfamily and it has been demonstrated to contribute to oxidative stress-mediated liver damage. The present study was aimed to determine the potential association between GSTM3 promoter methylation and oxidative stress in ACHBLF patients. Thirty ACHBLF patients, 30 CHB patients and 10 healthy controls were included in this study. Methylation of GSTM3 promoter was determined using methylation-specific PCR (MSP) method. Plasma biomarkers for oxidative stress including malondialdehyde (MDA) and GST were detected by enzyme-linked immunosorbent assay (ELISA). Model for end-stage liver disease (MELD) scoring system was used for predicting the severity and prognosis of liver failure. ACHBLF patients had significant higher GSTM3 promoter methylation rate than CHB patients (30% versus 6.7%, χ(2) = 5.455, P = 0.020). Plasma MDA and GST levels were significantly increased in ACHBLF patients compared with CHB patients. Meanwhile, MDA, MELD scores and mortality rate were significantly higher in methylated group than those in unmethylated group of ACHBLF patients. Furthermore, plasma MDA levels were positively correlated with MELD scores of ACHBLF (r = 0.588, P = 0.001). In conclusion, the methylation of GSTM3 promoter may contribute to oxidative stress-associated liver damage and correlate with the disease severity in ACHBLF.
Collapse
Affiliation(s)
- Li Qi
- Department of Hepatology, Qilu Hospital of Shandong University, Juan, PR, China
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
|