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Asgharzadeh F, Memarzia A, Alikhani V, Beigoli S, Boskabady MH. Peroxisome proliferator-activated receptors: Key regulators of tumor progression and growth. Transl Oncol 2024; 47:102039. [PMID: 38917593 PMCID: PMC11254173 DOI: 10.1016/j.tranon.2024.102039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 04/30/2024] [Accepted: 06/20/2024] [Indexed: 06/27/2024] Open
Abstract
One of the main causes of death on the globe is cancer. Peroxisome-proliferator-activated receptors (PPARs) are nuclear hormone receptors, including PPARα, PPARδ and PPARγ, which are important in regulating cancer cell proliferation, survival, apoptosis, and tumor growth. Activation of PPARs by endogenous or synthetic compounds regulates tumor progression in various tissues. Although each PPAR isotype suppresses or promotes tumor development depending on the specific tissues or ligands, the mechanism is still unclear. PPARs are receiving interest as possible therapeutic targets for a number of disorders. Numerous clinical studies are being conducted on PPARs as possible therapeutic targets for cancer. Therefore, this review will focus on the existing and future uses of PPARs agonists and antagonists in treating malignancies. PubMed, Science Direct, and Scopus databases were searched regarding the effect of PPARs on various types of cancers until the end of May 2023. The results of the review articles showed the therapeutic influence of PPARs on a wide range of cancer on in vitro, in vivo and clinical studies. However, further experimental and clinical studies are needed to be conducted on the influence of PPARs on various cancers.
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Affiliation(s)
- Fereshteh Asgharzadeh
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Arghavan Memarzia
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vida Alikhani
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Sima Beigoli
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Hossein Boskabady
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Zhang M, He S. Peroxisome proliferator-activated receptors regulate the progression and treatment of gastrointestinal cancers. Front Pharmacol 2023; 14:1169566. [PMID: 37025484 PMCID: PMC10070695 DOI: 10.3389/fphar.2023.1169566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 03/06/2023] [Indexed: 04/08/2023] Open
Abstract
Peroxisome proliferator-activated receptors (PPARs) are essential nuclear hormone receptors regulating metabolic processes, and they participate in the initiation and progression processes of tumors. Gastrointestinal (GI) cancer is a prevalent malignancy worldwide that originates from the tissues of the gastrointestinal tract and is characterized by severe symptoms and poor prognosis. Numerous published studies have investigated the critical role of PPARs in esophageal, gastric, and colorectal cancers. Here, we summarize and review the current literature to understand the role of PPARs in the pathogenesis of GI cancers and to provide a systematic reference for the subsequent investigation and development of efficient therapies targeting PPARs and their pathways.
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Affiliation(s)
- Min Zhang
- Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Shujie He
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Shujie He,
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Chen B, Wang Y, Tang W, Chen Y, Liu C, Kang M, Xie J. Association between PPARγ, PPARGC1A, and PPARGC1B genetic variants and susceptibility of gastric cancer in an Eastern Chinese population. BMC Med Genomics 2022; 15:274. [PMID: 36587194 PMCID: PMC9805199 DOI: 10.1186/s12920-022-01428-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 12/26/2022] [Indexed: 01/01/2023] Open
Abstract
PURPOSE Previous studies showed that peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator1 family (PPARGC1A and PPARGC1B) gene single nucleotide variants (SNVs)were strongly associated with cancer susceptibility. The purpose of this study was to investigate the association of PPARγ, PPARGC1A, and PPARGC1B variants with the risk of gastric cancer (GC). PATIENTS AND METHODS We performed a case-control study of 490 GC cases and 1,476 healthy controls from eastern China. PPARγ rs1801282 C > G, rs3856806 C > T, PPARGC1A rs2970847 C > T, rs8192678 C > T and PPARGC1B rs7732671 G > C, rs17572019 G > A SNVs were selected to investigate the association between these SNVs and GC susceptibility. Genotypes of the SNVs were assessed by multiplex fluorescent PCR using a custom-by-design 48-Plex SNPscantm Kit. RESULTS The PPARγ rs1801282 SNV was associated with a decreased risk for GC (GC vs. CC: odds ratio (OR) = 0.62, 95% confidence interval (95%CI) = 0.42-0.93, adjusted P = 0.019; GC + GG vs. GG: OR = 0.63 95%CI = 0.42-0.93, adjusted P = 0.019; respectively). In addition, stratified analysis revealed that the PPARγ rs1801282 SNV was correlated with the risk of GC in subgroups of age ≥ 61, no smoking, and no alcohol consuming. We also confirmed that the PPARγ rs3856806 C > T SNV promoted the risk of GC in women. The PPARGC1A rs8192678 TT genotype decreased the susceptibility of GC in men. The PPARGC1A rs2970847 C > T SNV decreased the susceptibility of GC in the subgroup of BMI ≥ 24 kg/m2. The PPARGC1B rs7732671 G > C and rs17572019 G > A SNVs promoted the risk of GC in the subgroup of BMI ≥ 24 kg/m2. CONCLUSION This study indicates that the PPARγ, PPARGC1A, and PPARGC1B SNVs may be associated with the susceptibility of GC in eastern Chinese population. Future studies with larger populations, detailed H. pylori infection status for subgroup analysis, and functional study are needed to further clarify the relationship between these SNVs and GC risk.
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Affiliation(s)
- Boyang Chen
- grid.440618.f0000 0004 1757 7156Department of Cardiothoracic Surgery, The Affiliated Hospital of Putian University, Putian, 351100 Fujian Province China
| | - Yafeng Wang
- Department of Cardiology, The People’s Hospital of Xishuangbanna Dai Autonomous Prefecture, Jinghong, Yunnan Province China
| | - Weifeng Tang
- grid.428392.60000 0004 1800 1685Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province China
| | - Yu Chen
- grid.415110.00000 0004 0605 1140Department of Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian Province China
| | - Chao Liu
- grid.452247.2Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu Province China
| | - Mingqiang Kang
- grid.440618.f0000 0004 1757 7156Department of Cardiothoracic Surgery, The Affiliated Hospital of Putian University, Putian, 351100 Fujian Province China ,grid.411176.40000 0004 1758 0478Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001 Fujian Province China
| | - Jinbiao Xie
- grid.440618.f0000 0004 1757 7156Department of Cardiothoracic Surgery, The Affiliated Hospital of Putian University, Putian, 351100 Fujian Province China
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Link A, Bornschein J, Thon C. Helicobacter pylori induced gastric carcinogenesis - The best molecular model we have? Best Pract Res Clin Gastroenterol 2021; 50-51:101743. [PMID: 33975683 DOI: 10.1016/j.bpg.2021.101743] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/19/2021] [Accepted: 03/25/2021] [Indexed: 01/31/2023]
Abstract
Gastric carcinogenesis can be described as a consequence of multilevel molecular alterations that is triggered by a cascade of events. Historically, diet and environmental factors have been identified to substantially contribute to carcinogenesis before the discovery of Helicobacter pylori (H. pylori). But H. pylori infection has revolutionized the understanding of gastric carcinogenesis. Although the model of H. pylori-driven carcinogenesis remains valid, there is a continuous effort to precisely delineate the molecular pathways involved and to understand the interplay with additional risk factors including recent relevant knowledge on the stomach microbiota. In this review, we provide an updated view on the models of gastric carcinogenesis. This includes historically appreciated H. pylori-induced models and expands these taking recent molecular data into consideration. Based on the data provided, we conclude that indeed H. pylori-carcinogenesis remains one of the best-established models at least for a subset of gastric cancers. Implementation of the recently identified molecular subtypes in novel genetic animal models is required to expand our knowledge on H. pylori-independent carcinogenesis.
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Affiliation(s)
- Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Section of Molecular Gastroenterology and Microbiota-associated Diseases, Otto-von-Guericke University, Magdeburg, Germany.
| | - Jan Bornschein
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford University Hospitals, Headington, Oxford, UK
| | - Cosima Thon
- Department of Gastroenterology, Hepatology and Infectious Diseases, Section of Molecular Gastroenterology and Microbiota-associated Diseases, Otto-von-Guericke University, Magdeburg, Germany
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Zuo X, Deguchi Y, Xu W, Liu Y, Li HS, Wei D, Tian R, Chen W, Xu M, Yang Y, Gao S, Jaoude JC, Liu F, Chrieki SP, Moussalli MJ, Gagea M, Sebastian MM, Zheng X, Tan D, Broaddus R, Wang J, Ajami NJ, Swennes AG, Watowich SS, Shureiqi I. PPARD and Interferon Gamma Promote Transformation of Gastric Progenitor Cells and Tumorigenesis in Mice. Gastroenterology 2019; 157:163-178. [PMID: 30885780 PMCID: PMC6581611 DOI: 10.1053/j.gastro.2019.03.018] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 02/20/2019] [Accepted: 03/12/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The peroxisome proliferator-activated receptor delta (PPARD) regulates cell metabolism, proliferation, and inflammation and has been associated with gastric and other cancers. Villin-positive epithelial cells are a small population of quiescent gastric progenitor cells. We expressed PPARD from a villin promoter to investigate the role of these cells and PPARD in development of gastric cancer. METHODS We analyzed gastric tissues from mice that express the Ppard (PPARD1 and PPARD2 mice) from a villin promoter, and mice that did not carry this transgene (controls), by histology and immunohistochemistry. We performed cell lineage-tracing experiments and analyzed the microbiomes, chemokine and cytokine production, and immune cells and transcriptomes of stomachs of these mice. We also performed immunohistochemical analysis of PPARD levels in 2 sets of human gastric tissue microarrays. RESULTS Thirty-eight percent of PPARD mice developed spontaneous, invasive gastric adenocarcinomas, with severe chronic inflammation. Levels of PPARD were increased in human gastric cancer tissues, compared with nontumor tissues, and associated with gastric cancer stage and grade. We found an inverse correlation between level of PPARD in tumor tissue and patient survival time. Gastric microbiomes from PPARD and control mice did not differ significantly. Lineage-tracing experiments identified villin-expressing gastric progenitor cells (VGPCs) as the origin of gastric tumors in PPARD mice. In these mice, PPARD up-regulated CCL20 and CXCL1, which increased infiltration of the gastric mucosa by immune cells. Immune cell production of inflammatory cytokines promoted chronic gastric inflammation and expansion and transformation of VGPCs, leading to tumorigenesis. We identified a positive-feedback loop between PPARD and interferon gamma signaling that sustained gastric inflammation to induce VGPC transformation and gastric carcinogenesis. CONCLUSIONS We found PPARD overexpression in VPGCs to result in inflammation, dysplasia, and tumor formation. PPARD and VGPCs might be therapeutic targets for stomach cancer.
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Affiliation(s)
- Xiangsheng Zuo
- Departments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
| | - Yasunori Deguchi
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Weiguo Xu
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yi Liu
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Haiyan S. Li
- Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Daoyan Wei
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Rui Tian
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Weidong Chen
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Min Xu
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yaying Yang
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Shen Gao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jonathan C. Jaoude
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Fuyao Liu
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Sarah P. Chrieki
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Micheline J. Moussalli
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Mihai Gagea
- Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Manu M. Sebastian
- Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Xiaofeng Zheng
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Dongfeng Tan
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Russell Broaddus
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jing Wang
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Nadim J. Ajami
- Alkek Center for Metagenomics and Microbiome Research and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Alton G. Swennes
- Center for Comparative Medicine and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Stephanie S. Watowich
- Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Imad Shureiqi
- Departments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Dhaini HR, Daher Z. Genetic polymorphisms of PPAR genes and human cancers: evidence for gene-environment interactions. JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH. PART C, ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS 2019; 37:146-179. [PMID: 31045458 DOI: 10.1080/10590501.2019.1593011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play a role in lipid metabolism, cell proliferation, terminal differentiation, apoptosis, and inflammation. Although several cancer models have been suggested to explain PPARs' involvement in tumorigenesis, however, their role is still unclear. In this review, we examined associations of the different PPARs, polymorphisms and various types of cancer with a focus on gene-environment interactions. Reviewed evidence suggests that functional genetic variants of the different PPARs may modulate the relationship between environmental exposure and cancer risk. In addition, this report unveils the scarcity of reliable quantitative environmental exposure data when examining these interactions, and the current gaps in studying gene-environment interactions in many types of cancer, particularly colorectal, prostate, and bladder cancers.
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Affiliation(s)
- Hassan R Dhaini
- a Department of Environmental Health, American University of Beirut , Lebanon
| | - Zeina Daher
- b Faculty of Public Health I, Lebanese University , Beirut , Lebanon
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Kountouras J, Polyzos SA, Doulberis M, Zeglinas C, Artemaki F, Vardaka E, Deretzi G, Giartza-Taxidou E, Tzivras D, Vlachaki E, Kazakos E, Katsinelos P, Mantzoros CS. Potential impact of Helicobacter pylori-related metabolic syndrome on upper and lower gastrointestinal tract oncogenesis. Metabolism 2018; 87:18-24. [PMID: 29936174 DOI: 10.1016/j.metabol.2018.06.008] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Revised: 06/18/2018] [Accepted: 06/19/2018] [Indexed: 12/12/2022]
Abstract
Both Helicobacter pylori infection and metabolic syndrome present significant global public health burdens. Metabolic syndrome is closely related to insulin resistance, the major underlying mechanism responsible for metabolic abnormalities, and Helicobacter pylori infection has been proposed to be a contributing factor. There is growing evidence for a potential association between Helicobacter pylori infection and insulin resistance, metabolic syndrome and related morbidity, including abdominal obesity, type 2 diabetes mellitus, dyslipidemia, hypertension, all of which increase mortality related to cardio-cerebrovascular disease, neurodegenerative disorders, nonalcoholic fatty liver disease and malignancies. More specifically, insulin resistance, metabolic syndrome and hyperinsulinemia have been associated with upper and lower gastrointestinal tract oncogenesis. Apart from cardio-cerebrovascular, degenerative diseases and nonalcoholic fatty liver disease, a number of studies claim that Helicobacter pylori infection is implicated in metabolic syndrome-related Barrett's esophagus and esophageal adenocarcinoma development, gastric and duodenal ulcers and gastric oncogenesis as well as lower gastrointestinal tract oncogenesis. This review summarizes evidence on the potential impact of Helicobacter pylori-related metabolic syndrome on gastroesophageal reflux disease-Barrett's esophagus-esophageal adenocarcinoma, gastric atrophy-intestinal metaplasia-dysplasia-gastric cancer and colorectal adenoma-dysplasia-colorectal cancer sequences. Helicobacter pylori eradication might inhibit these oncogenic processes, and thus further studies are warranted.
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Affiliation(s)
- Jannis Kountouras
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece.
| | - Stergios A Polyzos
- First Department of Pharmacology, Department of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Michael Doulberis
- Division of General Internal Medicine, University Hospital Inselspital of Bern, 3010 Bern, Switzerland
| | - Christos Zeglinas
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Fotini Artemaki
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Elizabeth Vardaka
- Department of Nutrition and Dietetics, Alexander Technological Educational Institute, Thessaloniki, Sindos, Macedonia, Greece
| | - Georgia Deretzi
- Department of Neurology, Papageorgiou General Hospital, Thessaloniki, Macedonia, Greece
| | | | | | - Efthymia Vlachaki
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Evangelos Kazakos
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Panagiotis Katsinelos
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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PPARG c.1347C>T polymorphism is associated with cancer susceptibility: from a case-control study to a meta-analysis. Oncotarget 2017; 8:102277-102290. [PMID: 29254243 PMCID: PMC5731953 DOI: 10.18632/oncotarget.20925] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 08/27/2017] [Indexed: 12/19/2022] Open
Abstract
Recently, several studies suggested that PPARG c.1347C>T polymorphism was correlated with cancer risk. However, past results remained controversial. In this study, we performed a case-control study on the relationship of PPARG c.1347C>T polymorphism with risk of non-small cell lung cancer (NSCLC) and subsequently carried out a meta-analysis to further assess the association between PPARG c.1347C>T and overall cancer. In our case-control study, after adjusting by age, sex, body mass index (BMI), smoking and drinking, a tendency to increased NSCLC risk was noted (CT/TT vs. CC: adjusted OR, 1.21; 95% CI, 0.97–1.51; P = 0.097). In the meta-analysis, we found a significant association between PPARG c.1347C>T polymorphism and overall cancer risk (T vs. C: OR, 1.13; 95% CI, 1.03–1.23; P = 0.006; TT vs. CC: OR, 1.29; 95% CI, 1.07–1.56; P = 0.008, CT/TT vs. CC: OR, 1.11; 95% CI, 1.02–1.21; P = 0.014 and TT vs. CT/CC: OR, 1.26; 95% CI, 1.04–1.52; P = 0.016). In a subgroup analysis by ethnicity, evidence of significant association between PPARG c.1347C>T polymorphism and cancer risk was found among Asians and mixed populations. In a subgroup analysis by cancer type, PPARG c.1347C>T polymorphism was associated with risk of esophageal cancer and glioblastoma. In addition, in a subgroup analysis by origin of cancer cell, evidence of significant association between PPARG c.1347C>T polymorphism and cancer risk was also found among epithelial tumor. In conclusion, the findings indicate PPARG c.1347C>T polymorphism may increase the susceptibility of cancer.
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Zhang RG, Duan GC, Fan QT, Chen SY. Role of Helicobacter pylori infection in pathogenesis of gastric carcinoma. World J Gastrointest Pathophysiol 2016; 7:97-107. [PMID: 26909232 PMCID: PMC4753193 DOI: 10.4291/wjgp.v7.i1.97] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 09/18/2015] [Accepted: 11/04/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common carcinoma and the second leading cause of cancer-related deaths worldwide. Helicobacter pylori (H. pylori) infection causes a series of precancerous lesions like gastritis, atrophy, intestinal metaplasia and dysplasia, and is the strongest known risk factor for GC, as supported by epidemiological, preclinical and clinical studies. However, the mechanism of H. pylori developing gastric carcinoma has not been well defined. Among infected individuals, approximately 10% develop severe gastric lesions such as peptic ulcer disease, 1%-3% progresses to GC. The outcomes of H. pylori infection are determined by bacterial virulence, genetic polymorphism of hosts as well as environmental factors. It is important to gain further understanding of the pathogenesis of H. pylori infection for developing more effective treatments for this common but deadly malignancy. The recent findings on the bacterial virulence factors, effects of H. pylori on epithelial cells, genetic polymorphism of both the bacterium and its host, and the environmental factors for GC are discussed with focus on the role of H. pylori in gastric carcinogenesis in this review.
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Ariffin H, Chan ASL, Oh L, Abd-Ghafar S, Ong GB, Mohamed M, Razali H, Juraida E, Teo SH, Karsa M, Shamsani J, Hainaut P. Frequent occurrence of gastric cancer in Asian kindreds with Li-Fraumeni syndrome. Clin Genet 2014; 88:450-5. [PMID: 25318593 DOI: 10.1111/cge.12525] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Revised: 09/24/2014] [Accepted: 10/13/2014] [Indexed: 11/28/2022]
Abstract
Type of cancer and age of onset in individuals with inherited aberrations in the tumour suppressor gene TP53 are variable, possibly influenced by genetic modifiers and different environmental exposure. Since 2009, the modified Chompret criteria (MCC) have been used to identify individuals for TP53 mutation screening. Using the TP53 mutation database maintained by the International Agency for Research on Cancer (IARC), we investigated if the MCC, mainly developed for a Caucasian population, was also applicable in Asia. We identified several differences in Asian families compared with similar Caucasian cohorts, suggesting that identification and management of Li-Fraumeni syndrome in Asia do not completely mirror that of North America and Western Europe. Early gastric cancer (<40 years) may be considered a new addition to the MCC especially for Asian families.
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Affiliation(s)
- H Ariffin
- University of Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia.,Paediatric Haematology-Oncology Unit, University of Malaya Medical Centre, Kuala Lumpur, Malaysia
| | - A S L Chan
- Paediatric Haematology-Oncology Unit, University of Malaya Medical Centre, Kuala Lumpur, Malaysia
| | - L Oh
- University of Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia
| | - S Abd-Ghafar
- University of Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia
| | - G B Ong
- Department of Paediatrics, Sarawak General Hospital, Sarawak, Malaysia
| | - M Mohamed
- Paediatrics Institute, Kuala Lumpur, Malaysia
| | - H Razali
- Department of Paediatrics, Sultan Ismail Hospital, Johor Bahru, Malaysia
| | - E Juraida
- Paediatrics Institute, Kuala Lumpur, Malaysia
| | - S H Teo
- Cancer Research Initiatives Foundation, Subang Jaya, Malaysia
| | - M Karsa
- University of Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia
| | - J Shamsani
- University of Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia
| | - P Hainaut
- Institut Albert Bonniot - INSERM 823, University Grenoble-Alpes, Grenoble, France
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Wang D, DuBois RN. PPARδ and PGE 2 signaling pathways communicate and connect inflammation to colorectal cancer. INFLAMMATION AND CELL SIGNALING 2014; 1. [PMID: 26290896 DOI: 10.14800/ics.338] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The nuclear hormone receptor peroxisome proliferator-activated receptor δ (PPARδ) is a ligand-dependent transcription factor that is involved in fatty acid metabolism, obesity, wound healing, inflammation, and cancer. Despite decades of research, the role of PPARδ in inflammation and colorectal cancer remains unclear and somewhat controversial. Our recent work presented the first genetic evidence demonstrating that PPARδ is required for chronic colonic inflammation and colitis-associated carcinogenesis. We also found that a PPARδ downstream pathway, namely the COX-2-derived PGE2 signaling, mediated crosstalk between tumor epithelial cells and macrophages to promote chronic inflammation and colitis-associated tumor genesis. In this brief review, we summarize recent studies on the role of PPARδ in inflammatory bowel disease (IBD) and colorectal cancer (CRC) and highlight recent advances in our understanding of how PPARδ and COX-2-drevided PGE2 signaling coordinately promote chronic colonic inflammation and colitis-associate tumorigenesis. Elucidating the role of PPARδ in inflammation and CRC may provide a rationale for development of PPARδ antagonists as new therapeutic agents in treatment of IBD and CRC.
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Affiliation(s)
- Dingzhi Wang
- Laboratory for Inflammation and Cancer, the Biodesign Institute at Arizona State University, Tempe, AZ 85287
| | - Raymond N DuBois
- Laboratory for Inflammation and Cancer, the Biodesign Institute at Arizona State University, Tempe, AZ 85287 ; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287 ; Department of Research and Division of Gastroenterology, Mayo Clinic, Scottsdale, AZ 85259
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