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Qu H, Yu Q, Ye L, Zheng J. SLC39A14 promotes the development of esophageal squamous cell carcinoma through PI3K/Akt/mTOR signaling pathway. Int Immunopharmacol 2025; 146:113831. [PMID: 39700956 DOI: 10.1016/j.intimp.2024.113831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 11/25/2024] [Accepted: 12/08/2024] [Indexed: 12/21/2024]
Abstract
OBJECTIVES This study aims to investigate the expression of solute carrier family 39 member 14 (SLC39A14) in esophageal squamous cell carcinoma (ESCC) tissues and its prognosis, as well as the impact of SLC39A14 expression on the biological behavior of ESCC cells and associated mechanisms. METHODS Bioinformatics analysis was utilized to compare the differential expression of SLC39A14 mRNA between esophageal cancer tissues and adjacent non-cancerous tissues. Immunohistochemistry was employed to evaluate SLC39A14 protein expression in human ESCC tissues and normal esophageal tissues, followed by an analysis of its association with clinicopathological parameters in esophageal cancer patients. Through cell proliferation, migration, invasion, and Western blot assays, we deeply evaluated the specific effects of SLC39A14 gene knockdown (or overexpression) on ESCC cells and explored its potential biological functions in ESCC. Subsequently, we validated the role of SLC39A14 in ESCC in a xenograft model. Furthermore, LY294002 drug intervention was used to verify the regulatory effect of SLC39A14 on PI3K/Akt/mTOR signaling pathway. RESULTS Both mRNA and protein levels of SLC39A14 were significantly elevated in tumor tissues from ESCC patients compared to adjacent normal tissues. Notably, higher levels of SLC39A14 expression positively correlated with ESCC tumor size (p = 0.010) and clinical T stage (p = 0.025), while exhibiting a negative correlation with overall patient survival rates (p = 0.023). In vitro experiments demonstrated that knocking down SLC39A14 significantly inhibited cell proliferation, migration and invasion. In vivo study showed that SLC39A14 facilitated progression within murine models bearing ESCC tumors. Mechanistic analyses suggested that pro-carcinogenic effects exerted by SLC39A14 are mediated through activation of the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS Our findings suggest that SLC39A14 may serve as a potential biomarker for ESCC due to its pro-oncogenic role during ESCC progression.
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Affiliation(s)
- Hangshuai Qu
- Department of Public Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang Province, China
| | - Qingxin Yu
- Department of pathology, Ningbo Clinical Pathology Diagnosis Center, Ningbo City, Zhejiang Province, China
| | - Luxia Ye
- Department of Public Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang Province, China
| | - Jingmin Zheng
- Department of Public Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang Province, China.
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Chew DCH, Yim CHH, Ali RA, El‐Omar EM. Epidemiology, Microbiome, and Risk Factors Involved in Carcinogenesis of Esophagus, Gastric, and Intestine. GASTROINTESTINAL ONCOLOGY ‐ A CRITICAL MULTIDISCIPLINARY TEAM APPROACH 2E 2024:2-22. [DOI: 10.1002/9781119756422.ch1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Wojnicka J, Grywalska E, Hymos A, Mertowska P, Mertowski S, Charytanowicz M, Klatka M, Klatka J, Dolliver WR, Błażewicz A. The Relationship between Cancer Stage, Selected Immunological Parameters, Epstein-Barr Virus Infection, and Total Serum Content of Iron, Zinc, and Copper in Patients with Laryngeal Cancer. J Clin Med 2024; 13:511. [PMID: 38256645 PMCID: PMC10816330 DOI: 10.3390/jcm13020511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 12/31/2023] [Accepted: 01/11/2024] [Indexed: 01/24/2024] Open
Abstract
(1) Background: the purpose of the study was to assess the relationship between cancer stage, selected immunological parameters, Epstein-Barr virus (EBV) infection, and total serum content of iron, zinc, and copper in patients with laryngeal cancer (LC). (2) Methods: serum Fe, Zn, and Cu were measured in 40 LC patients and 20 controls. Immunophenotyping of peripheral blood lymphocytes was performed by flow cytometry using fluorescent antibodies against CD3, CD4, CD8, CD19, CD25, CD69, and PD-1. Tumor and lymph node lymphocytes were analyzed by flow cytometry. EBV DNA was quantified by real-time PCR, targeting the EBNA-1 gene. Associations between serum elements, immune markers, and cancer grade/stage were evaluated using ANOVA and appropriate nonparametric tests. (3) Results: levels of Fe, Cu, and Zn were lower, while Cu/Zn was statistically higher, in patients with LC than in the control group. Correlation analysis showed a statistically significant association between the levels of these elements and parameters of the TNM (Tumor, Node, Metastasis) staging system, immunophenotype, and the amount of EBV genetic material in patients with LC who survived for more than 5 years. (4) Conclusion: the results suggest that the total serum levels of the determined micronutrients may significantly affect the immunopathogenesis and progression of LC.
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Affiliation(s)
- Julia Wojnicka
- Department of Pathobiochemistry and Interdisciplinary Applications of Ion Chromatography, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland;
| | - Ewelina Grywalska
- Department of Experimental Immunology, Medical University of Lublin, 4a Chodźki Street, 20-093 Lublin, Poland; (E.G.); (A.H.); (P.M.); (S.M.)
| | - Anna Hymos
- Department of Experimental Immunology, Medical University of Lublin, 4a Chodźki Street, 20-093 Lublin, Poland; (E.G.); (A.H.); (P.M.); (S.M.)
| | - Paulina Mertowska
- Department of Experimental Immunology, Medical University of Lublin, 4a Chodźki Street, 20-093 Lublin, Poland; (E.G.); (A.H.); (P.M.); (S.M.)
| | - Sebastian Mertowski
- Department of Experimental Immunology, Medical University of Lublin, 4a Chodźki Street, 20-093 Lublin, Poland; (E.G.); (A.H.); (P.M.); (S.M.)
| | - Małgorzata Charytanowicz
- Department of Computer Science, Faculty of Electrical Engineering and Computer Science, Lublin University of Technology, Nadbystrzycka 38D, 20-618 Lublin, Poland;
- Systems Research Institute, Polish Academy of Sciences, Newelska 6, 01-447 Warsaw, Poland
| | - Maria Klatka
- Department of Pediatric Endocrinology and Diabetology, Medical University, Gębali 1 St., 20-093 Lublin, Poland;
| | - Janusz Klatka
- Department of Otolaryngology and Laryngological Oncology, Medical University of Lublin, Jaczewskiego 8 St., 20-954 Lublin, Poland;
| | | | - Anna Błażewicz
- Department of Pathobiochemistry and Interdisciplinary Applications of Ion Chromatography, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland;
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Chen B, Yu P, Chan WN, Xie F, Zhang Y, Liang L, Leung KT, Lo KW, Yu J, Tse GMK, Kang W, To KF. Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets. Signal Transduct Target Ther 2024; 9:6. [PMID: 38169461 PMCID: PMC10761908 DOI: 10.1038/s41392-023-01679-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Revised: 09/15/2023] [Accepted: 10/10/2023] [Indexed: 01/05/2024] Open
Abstract
Zinc metabolism at the cellular level is critical for many biological processes in the body. A key observation is the disruption of cellular homeostasis, often coinciding with disease progression. As an essential factor in maintaining cellular equilibrium, cellular zinc has been increasingly spotlighted in the context of disease development. Extensive research suggests zinc's involvement in promoting malignancy and invasion in cancer cells, despite its low tissue concentration. This has led to a growing body of literature investigating zinc's cellular metabolism, particularly the functions of zinc transporters and storage mechanisms during cancer progression. Zinc transportation is under the control of two major transporter families: SLC30 (ZnT) for the excretion of zinc and SLC39 (ZIP) for the zinc intake. Additionally, the storage of this essential element is predominantly mediated by metallothioneins (MTs). This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression, with a special focus on cancer. We also compile a summary of clinical trials involving zinc ions. Given the main localization of zinc transporters at the cell membrane, the potential for targeted therapies, including small molecules and monoclonal antibodies, offers promising avenues for future exploration.
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Affiliation(s)
- Bonan Chen
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China
| | - Peiyao Yu
- Department of Pathology, Nanfang Hospital and Basic Medical College, Southern Medical University, Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China
| | - Wai Nok Chan
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China
| | - Fuda Xie
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China
| | - Yigan Zhang
- Institute of Biomedical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Li Liang
- Department of Pathology, Nanfang Hospital and Basic Medical College, Southern Medical University, Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China
| | - Kam Tong Leung
- Department of Pediatrics, The Chinese University of Hong Kong, Hong Kong, China
| | - Kwok Wai Lo
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Jun Yu
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Gary M K Tse
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Wei Kang
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
- CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
| | - Ka Fai To
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
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Hashemian M, Poustchi H, Sharafkhah M, Pourshams A, Mohammadi-Nasrabadi F, Hekmatdoost A, Malekzadeh R. Iron, Copper, and Magnesium Concentration in Hair and Risk of Esophageal Cancer: A Nested Case-Control Study. ARCHIVES OF IRANIAN MEDICINE 2023; 26:665-670. [PMID: 38431946 PMCID: PMC10915918 DOI: 10.34172/aim.2023.98] [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: 06/05/2023] [Accepted: 10/14/2023] [Indexed: 03/05/2024]
Abstract
BACKGROUND An association has already been hypothesized between iron, copper, and magnesium status assessed through food frequency questionnaires (FFQs) and the risk of esophageal squamous cell carcinoma (ESCC). However, self-reported dietary assessment methods are prone to measurement errors. We studied the association between iron, copper, and magnesium status and ESCC risk, using hair samples as a long exposure biomarker. METHODS We designed a nested case-control study within the Golestan Cohort Study, that recruited about 50000 participants in 2004-2008, and collected biospecimens at baseline. We identified 96 incident cases of ESCC with available hair samples. They were age-matched with cancer-free controls from the cohort. We used inductively coupled plasma mass spectrometry (ICP-MS) to measure iron, copper, and magnesium concentrations in hair samples. We used multiple logistic regression models to determine odds ratios and 95% confidence intervals. RESULTS Median concentrations of iron, copper, and magnesium were 35.4, 19.3, and 41.7 ppm in cases and 25.8, 18.3, and 50.0 ppm in controls, respectively. Iron was significantly associated with the risk of ESCC in continuous analysis (OR=1.41, 95% CI=1.03-1.92), but not in the tertiles analyses (ORT3 vs. T1=1.81, 95% CI=0.77-4.28). No associations were observed between copper and magnesium and ESCC risk, in either the tertiles models or the continuous estimate (copper: ORT3 vs. T1=2.56, 95% CI=1.00-6.54; magnesium: ORT3 vs. T1=0.75, 95% CI=0.32-1.78). CONCLUSION Higher iron status may be related to a higher risk of ESCC in this population.
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Affiliation(s)
- Maryam Hashemian
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Biology Department, School of Arts and Sciences, Utica University, Utica, NY, USA
| | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Sharafkhah
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Akram Pourshams
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Mohammadi-Nasrabadi
- Food and Nutrition Policy and Planning Research Department, National Nutrition and Food Technology Research Institute (NNFTRI), Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Departments of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Lander S, Lander E, Gibson MK. Esophageal Cancer: Overview, Risk Factors, and Reasons for the Rise. Curr Gastroenterol Rep 2023; 25:275-279. [PMID: 37812328 DOI: 10.1007/s11894-023-00899-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2023] [Indexed: 10/10/2023]
Abstract
PURPOSE OF REVIEW Esophageal cancer (EC) is a common cancer affecting many regions of the world and carries significant morbidity and mortality. In this article, we review the key risk factors and their associated impact on the changing incidence and prevalence of EC subtypes within different global regions. We also highlight potential reasons for the ever-changing epidemiology of this prevalent cancer type. RECENT FINDINGS There has been a shift in incidence of Esophageal Adenocarcinoma (AC) and Squamous Cell Carcinoma (SCC) within certain populations primarily due to an increase prevalence of primary risk factors. In Western nations, more often the United States, there has been a shift from SCC predominance to the majority of new cases of EC being adenocarcinoma. This shift within the United States has largely correlated with a rise in obesity. The prevalence of AC in Asia is also starting to rise as more countries adopt a western diet. The pathophysiology, associated risk factors, and presentation of ESCC and AC are different. This difference is seen in varying lifestyles, population health, and certain genetic risks. With further development closer analysis of primary risk factors and implementation of policies and programs that promote public health literacy, there is a potential to decrease esophageal cancer's global disease burden.
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Affiliation(s)
- Steve Lander
- Department of Medicine, The University of Tennessee Health Sciences Center, Memphis, TN, USA.
| | - Eric Lander
- Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Michael K Gibson
- Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
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Fong L, Huebner K, Jing R, Smalley K, Brydges C, Fiehn O, Farber J, Croce C. Zinc treatment reverses and anti-Zn-regulated miRs suppress esophageal carcinomas in vivo. Proc Natl Acad Sci U S A 2023; 120:e2220334120. [PMID: 37155893 PMCID: PMC10193985 DOI: 10.1073/pnas.2220334120] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 04/04/2023] [Indexed: 05/10/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% decrease in ESCC incidence vs. Zn-untreated controls. Zn treatment eliminated ESCCs by affecting a spectrum of biological processes that included downregulation of expression of the two miRs and miR-31-controlled inflammatory pathway, stimulation of miR-21-PDCD4 axis apoptosis, and reversal of the ESCC metabolome: with decrease in putrescine, increase in glucose, accompanied by downregulation of metabolite enzymes ODC and HK2. Thus, Zn treatment or miR-31/21 silencing are effective therapeutic strategies for ESCC in this rodent model and should be examined in the human counterpart exhibiting the same biological processes.
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Affiliation(s)
- Louise Y. Fong
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA19107
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA19107
| | - Kay Huebner
- Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH43210
| | - Ruiyan Jing
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA19107
| | - Karl J. Smalley
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA19107
| | - Christopher R. Brydges
- NIH West Coast Metabolomics Center, The Genome Center, University of California, Davis, CA95616
| | - Oliver Fiehn
- NIH West Coast Metabolomics Center, The Genome Center, University of California, Davis, CA95616
| | - John L. Farber
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA19107
| | - Carlo M. Croce
- Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH43210
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Sheikh M, Roshandel G, McCormack V, Malekzadeh R. Current Status and Future Prospects for Esophageal Cancer. Cancers (Basel) 2023; 15:765. [PMID: 36765722 PMCID: PMC9913274 DOI: 10.3390/cancers15030765] [Citation(s) in RCA: 102] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 01/10/2023] [Accepted: 01/20/2023] [Indexed: 01/28/2023] Open
Abstract
Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological subtypes with distinct epidemiological and clinical features. While the global incidence of ESCC is declining, the incidence of EAC is increasing in many countries. Decades of epidemiologic research have identified distinct environmental exposures for ESCC and EAC subtypes. Recent advances in understanding the genomic aspects of EC have advanced our understanding of EC causes and led to using specific genomic alterations in EC tumors as biomarkers for early diagnosis, treatment, and prognosis of this cancer. Nevertheless, the prognosis of EC is still poor, with a five-year survival rate of less than 20%. Currently, there are significant challenges for early detection and secondary prevention for both ESCC and EAC subtypes, but Cytosponge™ is shifting this position for EAC. Primary prevention remains the preferred strategy for reducing the global burden of EC. In this review, we will summarize recent advances, current status, and future prospects of the studies related to epidemiology, time trends, environmental risk factors, prevention, early diagnosis, and treatment for both EC subtypes.
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Affiliation(s)
- Mahdi Sheikh
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | - Gholamreza Roshandel
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 49341-74515, Iran
| | - Valerie McCormack
- Environment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran 14117-13135, Iran
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Yang X, Tang Z, Li J, Jiang J. Esophagus cancer and essential trace elements. Front Public Health 2022; 10:1038153. [PMID: 36466456 PMCID: PMC9709130 DOI: 10.3389/fpubh.2022.1038153] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 10/19/2022] [Indexed: 11/17/2022] Open
Abstract
Numerous epidemiological and laboratory studies on essential trace elements have reported protective associations in developing various cancer types, including esophagus cancer (EC). However, the results are not always consistent. Some essential trace elements could play a vital role in preventing esophagus cancer. Some showed no association with esophageal cancer risk, while others harmed individuals. This article reviews the association between the intake or supplementation of essential trace elements (especially zinc, copper, iron, and selenium) and the risk of esophageal cancer. Generally, zinc intake may decrease the risk of esophageal cancer (EC), especially in high esophageal squamous cell carcinoma (ESCC) prevalence regions. The association between copper supplementation and EC remains uncertain. Total iron consumption is thought to be associated with lower EC risk, while heme iron intake may be associated with higher EC risk. Selenium intake showed a protective effect against EC, especially for those individuals with a low baseline selenium level. This review also prospects the research direction of the association between EC and essential trace elements.
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Affiliation(s)
- Xin Yang
- Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhe Tang
- Department of Thoracic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Li
- Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jizong Jiang
- Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,*Correspondence: Jizong Jiang
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Zhang J, Wang G, Huang A, Cao K, Tan W, Geng H, Lin X, Zhan F, Wu K, Zheng S, Liu C. Association between Serum Level of Multiple Trace Elements and Esophageal Squamous Cell Carcinoma Risk: A Case-Control Study in China. Cancers (Basel) 2022; 14:4239. [PMID: 36077776 PMCID: PMC9455051 DOI: 10.3390/cancers14174239] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/21/2022] [Accepted: 08/29/2022] [Indexed: 02/07/2023] Open
Abstract
We investigated the associations between multiple serum trace element levels and risk for esophageal squamous cell carcinoma (ESCC). A total of 185 ESCC patients and 191 healthy individuals were recruited in our study. The concentration of 13 trace elements (Al, V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Sr, Cd and Pb) in serum was determined with inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression and the Probit extension of Bayesian Kernel Machine Regression (BKMR) models was established to explore the associations and the cumulative and mixed effects of multiple trace elements on ESCC. Three elements (Zn, Se and Sr) displayed a negative trend with risk for ESCC, and a significant overall effect of the mixture of Al, V, Mn, Ni, Zn, Se and Sr on ESCC was found, with the effects of V, Ni and Sr being nonlinear. Bivariate exposure-response interactions among these trace elements indicated a synergistic effect between Zn and Se, and an impactful difference of V combined with Ni, Sr or Zn. Our results indicate that Ni, V, Al, Mn, Zn, Se and Sr are associated with ESCC risk, providing additional evidence of the complex effects of trace elements disorder during the etiology of EC development.
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Affiliation(s)
- Jingbing Zhang
- Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, China
| | - Geng Wang
- Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, Shantou 515041, China
| | - Anyan Huang
- Mental Health Center, Shantou University Medical College, Shantou 515065, China
| | - Kexin Cao
- Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, China
| | - Wei Tan
- Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, China
| | - Hui Geng
- Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, China
| | - Xiaosheng Lin
- Health Management Center, The People’s Hospital of Jieyang, Jieyang 522000, China
| | - Fulan Zhan
- Department of Ultrasound, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
| | - Kusheng Wu
- Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, China
| | - Shukai Zheng
- Department of Burns and Plastic Surgery, and Cleft Lip and Palate Treatment Center, Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
| | - Caixia Liu
- Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, China
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Ben Elouefi R, Saâdaoui F. Inverse‐Probability‐Weighted Logrank Test for Stratified Survival Data with Missing Measurements. STAT NEERL 2022. [DOI: 10.1111/stan.12276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Rim Ben Elouefi
- École Supérieure Privée d'Ingénierie et de Technologie, Pôle Technologique El Ghazala Tunis Tunisia
| | - Foued Saâdaoui
- Department of Statistics, Faculty of Sciences King Abdulaziz University, P.O BOX 80203 Jeddah Saudi Arabia
- University of Sousse, Institut des Hautes Etudes Commerciales (IHEC), Route Hzamia, Sahloul 3, B.P. 40 Sousse Tunisia
- Lab: LR18ES15 Algèbre, Théorie de Nombres et Analyse Non‐linéaire, Faculté des Sciences Monastir Tunisia
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Jin J, Guo D, Wang Y, Jiao W, Li D, He Y. Artesunate Inhibits the Development of Esophageal Cancer by Targeting HK1 to Reduce Glycolysis Levels in Areas With Zinc Deficiency. Front Oncol 2022; 12:871483. [PMID: 35646662 PMCID: PMC9133444 DOI: 10.3389/fonc.2022.871483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 04/11/2022] [Indexed: 11/13/2022] Open
Abstract
Esophageal cancer (EC) threatens many lives in China, especially in areas with high incidences of EC. Our previous studies proved that zinc deficiency (ZD) promotes the cell cycle, thus promoting the progression of EC in areas with a high incidence of EC. Artesunate could inhibit the cell cycle, thereby inhibiting the progression of EC. In this study, we first demonstrated the mechanism by which artesunate inhibits EC in vitro and then demonstrated that artesunate could reverse the ZD-promoted progression of EC before EC occurred in vivo. The results showed that artesunate could inhibit the cell cycle, metastasis, and glycolysis of EC cells. Artesunate could target HK1, promote HK1 degradation, and reduce the levels of HIF-1α and PKM2 expression, which are key glycolysis enzymes. The in vivo results showed that ZD could increase the expression of HK1 and increase the incidence of EC. Artesunate reduced the incidence of EC and decreased the level of HK1 expression before EC occurred. Artesunate has an anti-EC effect by inhibiting aerobic glycolysis and has the potential to be a drug that prevents EC in areas with a high risk of EC.
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Affiliation(s)
- Jing Jin
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Dongli Guo
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yingying Wang
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Wenpeng Jiao
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Daojuan Li
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yutong He
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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Su F, Fang Y, Yu J, Jiang T, Lin S, Zhang S, Lv L, Long T, Pan H, Qi J, Zhou Q, Tang W, Ding G, Wang L, Tan L, Yin J. The Single Nucleotide Polymorphisms of AP1S1 are Associated with Risk of Esophageal Squamous Cell Carcinoma in Chinese Population. Pharmgenomics Pers Med 2022; 15:235-247. [PMID: 35321090 PMCID: PMC8938157 DOI: 10.2147/pgpm.s342743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 01/24/2022] [Indexed: 12/24/2022] Open
Abstract
Background The σ1A subunit of the adaptor protein 1 (AP1S1) participates in various intracellular transport pathways, especially the maintenance of copper homeostasis, which is pivotal in carcinogenesis. It is therefore rational to presume that AP1S1 might also be involved in carcinogenesis. In this hospital-based case-control study, we investigated the genetic susceptibility to ESCC in relation to SNPs of AP1S1 among Chinese population. Methods A database containing a total of 1303 controls and 1043 ESCC patients were retrospectively studied. The AP1S1 SNPs were analyzed based on ligation detection reaction (LDR) method. Then, the relationship between ESCC and SNPs of AP1S1 was determined with a significant crude P<0.05. Then the logistic regression analysis was used for the calculation for adjusted P in the demographic stratification comparison if a significant difference was observed in the previous step. Results AP1S1 rs77387752 C>T genotype TT was an independent risk factor for ESCC, while rs4729666 C>T genotype TC and rs35208462 C>T genotype TC were associated with a lower risk for ESCC, especially in co-dominant model and allelic test for younger, male subjects who are not alcohol-drinkers nor cigarette smokers. Conclusion AP1S1 rs77387752, rs4729666 and rs35208462 polymorphisms are associated with susceptibility to ESCC in Chinese individuals. AP1S1 SNPs may exert an important role in esophageal carcinogenesis and could serve as potential diagnostic biomarkers.
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Affiliation(s)
- Feng Su
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China
| | - Yong Fang
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China
| | - Jinjie Yu
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China
| | - Tian Jiang
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China
| | - Siyun Lin
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China
| | - Shaoyuan Zhang
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China
| | - Lu Lv
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Jiangsu, People’s Republic of China
| | - Tao Long
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Jiangsu, People’s Republic of China
| | - Huiwen Pan
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Jiangsu, People’s Republic of China
| | - Junqing Qi
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Jiangsu, People’s Republic of China
| | - Qiang Zhou
- Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan, People’s Republic of China
| | - Weifeng Tang
- Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Jiangsu, People’s Republic of China
| | - Guowen Ding
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Jiangsu, People’s Republic of China
| | - Liming Wang
- Department of Respiratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China
| | - Lijie Tan
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China
| | - Jun Yin
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China
- Correspondence: Jun Yin; Lijie Tan, Zhongshan Hospital of Fudan University, 180 Fenglin road, Xuhui District, Shanghai, 200032, People’s Republic of China, Email ;
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Lipenga T, Matumba L, Vidal A, Herceg Z, McCormack V, De Saeger S, De Boevre M. A concise review towards defining the exposome of oesophageal cancer in sub-Saharan Africa. ENVIRONMENT INTERNATIONAL 2021; 157:106880. [PMID: 34543937 DOI: 10.1016/j.envint.2021.106880] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 09/11/2021] [Accepted: 09/13/2021] [Indexed: 06/13/2023]
Abstract
CONTEXT Oesophageal cancer (EC) is among the common causes of illness and death among all cancers worldwide. Advanced EC has a poor prognosis, with worse outcomes observed in low-income settings. Oesophageal squamous cell carcinoma (ESCC) is the most common EC histology reported globally, with the highest ESCC incidence rates in the 'Asian Belt' and the African EC corridor. While the aetiology of ESCC is well-documented in the 'Asian belt', data for the African EC corridor and the entirety of sub-Saharan Africa (SSA) are fewer. OBJECTIVE To help address gaps in ESCC aetiology in SSA, we critically evaluated evidence of lifestyle, environmental, and epigenetic factors associated with ESCC risk and discussed prospects of defining ESCC exposome. DATA INCLUSION Unlimited English and non-English articles search were made on PubMed Central and Web of Science databases from January 1970 to August 2021. In total, we retrieved 999 articles and considered meta-analyses, case-control, and cohort studies. The quality of individual studies was assessed using the Newcastle-Ottawa scale. DATA EXTRACTION Details extracted include the year of publication, country of origin, sample size, comparators, outcomes, study subjects, and designs. DATA ANALYSIS Together, we assessed 13 case-control studies and two meta-analyses for the effect of lifestyle or environmental exposures on ESCC risk. Again, we evaluated seven case-control studies and one meta-analysis regarding the role of epigenetics in ESCC tumorigenesis. RESULTS In general, evidence of ESCC aetiology points to essential contributions of alcohol, tobacco, hot beverages, biomass fuel, and poor oral health/hygiene, although more precise risk characterisation remains necessary. CONCLUSION We conclude that ESCC in SSA is a multifactorial disease initiated by several external exposures that may induce aberrant epigenetic changes. The expanding aetiological research in this domain will be enhanced by evidence synthesis from classical and molecular epidemiological studies spanning the external and internal exposome.
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Affiliation(s)
- Trancizeo Lipenga
- Department of Bioanalysis, Centre of Excellence in Mycotoxicology and Public Health, Ghent University, Ghent, Belgium; Department of Pathology, Kamuzu University of Health Sciences (KUHeS), Blantyre, Malawi; MYTOX-SOUTH, International Thematic Network, Ghent University, Ghent, Belgium; CRIG, Cancer Research Institute Ghent, Ghent, Belgium.
| | - Limbikani Matumba
- MYTOX-SOUTH, International Thematic Network, Ghent University, Ghent, Belgium; Food Technology and Nutrition Research Group-NRC, Lilongwe University of Agriculture and Natural Resources, Lilongwe, Malawi
| | - Arnau Vidal
- Department of Bioanalysis, Centre of Excellence in Mycotoxicology and Public Health, Ghent University, Ghent, Belgium; MYTOX-SOUTH, International Thematic Network, Ghent University, Ghent, Belgium
| | - Zdenko Herceg
- Epigenomics and Mechanism Branch, International Agency for Research on Cancer (WHO-IARC), Lyon, France
| | - Valerie McCormack
- Environment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer (WHO-IARC), Lyon, France
| | - Sarah De Saeger
- Department of Bioanalysis, Centre of Excellence in Mycotoxicology and Public Health, Ghent University, Ghent, Belgium; MYTOX-SOUTH, International Thematic Network, Ghent University, Ghent, Belgium; CRIG, Cancer Research Institute Ghent, Ghent, Belgium; Department of Biotechnology and Food Technology, Faculty of Science, University of Johannesburg, Doornfontein Campus, Gauteng, South Africa
| | - Marthe De Boevre
- Department of Bioanalysis, Centre of Excellence in Mycotoxicology and Public Health, Ghent University, Ghent, Belgium; MYTOX-SOUTH, International Thematic Network, Ghent University, Ghent, Belgium; CRIG, Cancer Research Institute Ghent, Ghent, Belgium
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15
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Chen Y, Liu FX, Liu H. Effects of dietary zinc deficiency on esophageal squamous cell proliferation and the mechanisms involved. World J Gastrointest Oncol 2021; 13:1755-1765. [PMID: 34853648 PMCID: PMC8603456 DOI: 10.4251/wjgo.v13.i11.1755] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/30/2021] [Accepted: 09/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Dietary zinc deficiency has been shown to be associated with the development of esophageal cancer in humans, but the exact mechanism of action is not known
AIM To observe the effects of dietary zinc deficiency on esophageal squamous cell proliferation.
METHODS Thirty C57BL/6 mice were randomly divided into three groups: A zinc-sufficient (ZS) group, zinc-deficient (ZD) group, and zinc-replenished (ZR) group. For weeks 1–10, zinc levels in the mice diets were 30.66–30.89 mg/kg in the ZS group and 0.66–0.89 mg/kg in the ZD and ZR groups. During weeks 10–12, the ZR group was switched to the ZS diet; the other two groups had no changes in their diets. Changes in body weight, serum, and esophageal tissue zinc concentrations were assessed as well as differences in the expression of proliferating cell nuclear antigen (PCNA), mitogen-activated protein kinase p38 (p38MAPK), nuclear factor kappa B (NF-κB) p105, NF-κB p65, and cyclooxygenase (COX)-2 proteins in the esophageal mucosa.
RESULTS The body weight and zinc concentration in the serum and esophageal mucosa were significantly lower in the ZD and ZR groups than in the ZS group (P < 0.05). In ZD mice, there was a marked proliferation of basal cells in the esophageal mucosa, resulting in a disturbance in the arrangement of basal cells in layers 2–4, a thickening of the squamous layer, and a significant increase in the expression of the above-mentioned five proteins involved in proliferation and inflammation in the esophageal mucosa. Two weeks after switching to the ZS diet, the serum zinc concentration in the ZR group increased, and the expression of PCNA, NF-κB p105, and COX-2 decreased, but the concentration of zinc in the esophageal mucosa and the structure of the esophageal mucosa did not display any significant changes
CONCLUSION The ZD diet decreased the growth rate and promoted the proliferation of esophageal squamous cells in mice. The mechanism of proliferation was related to the induced overexpression of COX-2, P38, PCNA, and NF-κB (p105 and p65), and the ZR diet reduced the expression of PCNA, NF-κB p105, and COX-2, thereby reversing this process.
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Affiliation(s)
- Yao Chen
- Department of Traditional Chinese Medicine, Peking University International Hospital, Beijing 102206, China
| | - Fang-Xun Liu
- International Medical Center, Peking University International Hospital, Beijing 102206, China
| | - Hong Liu
- Department of Gastroenterology, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, China
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16
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CDKN1A (p21 gene) polymorphisms correlates with age in esophageal cancer. Mol Biol Rep 2021; 49:249-258. [PMID: 34743275 DOI: 10.1007/s11033-021-06865-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 10/20/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND CDKN1A gene encoding p21 is an important tumour supressor involved in the pathogenesis of cancers. A few studies have been devoted to the association between CDKN1A single nucleotide polymorphisms (SNPs) and esophageal cancer (EC) in China, India and Iran. The aim of this case-control study was to investigate the association of CDKN1A polymorphisms with EC risk in the Turkey population for the first time. METHODS In the present study, CDKN1A SNPs (rs1801270 C > T, rs1059234 C > A and rs3176352 C > G) were genotyped with the use of TaqMan SNP genotyping assays in 102 patients and 119 controls. RESULTS The genotypes and alleles of CDKN1A SNPs were not significantly different among patients and controls. However, TT-genotype and T-allele of the rs1059234, the rs1801270 CC-genotype and rs3176352 G-allele were significantly associated with EC risk for ≤ 55 age (p < 0.05). In those over 55 age, CC-genotype and C-allele of the rs1059234 was significantly associated with EC (p < 0.05). The rs1059234 T-carriers had a higher risk of high globulin level (p = 0.017) and low albumin/globulin ratio (p = 0.019) when compared to non-T carriers (CC). The rs3176352 CC-genotype carriers had a higher risk of esophageal adenocarcinoma (EAC) subtype when compared to CG-genotype carriers and CG-genotype carriers had a higher risk of squamous cell carcinoma (ESCC) subtype (OR/95% CI = 4.00/1.06-15.08, p = 0.04). The rs3176352 CC-genotype is also a risk factor for the higher BMI (p = 0.04) and the higher CA-19-9 level (p = 0.009). CONCLUSION Our study suggests that the CDKN1A polymorphisms may play an important role in EC risk in relation to age. Future studies are needed to validate our findings.
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17
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Li J, Xu J, Zheng Y, Gao Y, He S, Li H, Zou K, Li N, Tian J, Chen W, He J. Esophageal cancer: Epidemiology, risk factors and screening. Chin J Cancer Res 2021; 33:535-547. [PMID: 34815628 PMCID: PMC8580797 DOI: 10.21147/j.issn.1000-9604.2021.05.01] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 10/11/2021] [Indexed: 01/06/2023] Open
Abstract
More than 600,000 people are diagnosed with esophageal cancer (EC) every year globally, and the five-year survival rate of EC is less than 20%. Two common histological subtypes of EC, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have great geographical variations in incidence rates. About half of the world's EC was diagnosed in China and a majority of which belong to ESCC. Globally, the overall incidence rate of EC is decreasing. In some high-risk Asian regions, such as China, the incidence rate of ESCC has generally declined, potentially due to economic growth and improvement of diet habits. In some European high-income countries and the United States, the decline is mainly attributed to the decrease in smoking and drinking. The risk factors of EC are not well understood, and the importance of environmental and genetic factors in the pathogenesis is also unclear. The incidence and mortality of advanced EC can be reduced through early diagnosis and screening. White light endoscopy is still the gold standard in the current screening technology. This article reviews the epidemiology, risk factors, and screening strategies of EC in recent years to help researchers determine the most effective management strategies to reduce the risk of EC.
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Affiliation(s)
- Jiang Li
- Office for Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.,Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Beijing 100021, China
| | - Jianguo Xu
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Yadi Zheng
- Office for Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ya Gao
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Siyi He
- Office for Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - He Li
- Office for Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Kaiyong Zou
- Office for Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ni Li
- Office for Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.,Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Beijing 100021, China
| | - Jinhui Tian
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.,Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou University, Lanzhou 730000, China
| | - Wanqing Chen
- Office for Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.,Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Beijing 100021, China
| | - Jie He
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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18
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Grille VJ, Campbell S, Gibbs JF, Bauer TL. Esophageal cancer: the rise of adenocarcinoma over squamous cell carcinoma in the Asian belt. J Gastrointest Oncol 2021; 12:S339-S349. [PMID: 34422398 PMCID: PMC8343081 DOI: 10.21037/jgo-2019-gi-08] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 08/17/2020] [Indexed: 12/12/2022] Open
Abstract
Esophageal cancer is a common cancer worldwide with a high associated mortality rate. Amongst the two most frequent subsets of disease, squamous cell carcinoma (SCC) and adenocarcinoma (AC), there has been an epidemiologic shift towards adenocarcinoma over the last few decades. However, squamous cell carcinoma still predominates worldwide. Within Western countries, obesity has been associated with an increase in esophageal AC. A striking report from the World Health Organization (WHO) stated that worldwide obesity has tripled since 1975. In 2016, the WHO reported that greater than 1.9 billion adults are overweight and over 650 million were obese. In this review our goal is to analyze the esophageal cancer trends of China, which is the largest contributor among the esophageal cancer "Asian belt." Our intent is to evaluate whether there is a correlation between the rise in esophageal adenocarcinoma and obesity in this esophageal cancer "hotspot." With further analysis, the high-risk populations that are identified can be targeted to implement preventative strategies. This focus will aid in decreasing the burden of esophageal cancer at the global health level by addressing preventative strategies, such as screening endoscopy and lifestyle modifications. For example, WHO developed a global action plan on physical activity in response to the rise in obesity worldwide. Prevention is key to decreasing the rate of esophageal adenocarcinoma as majority of cases are diagnosed in the late stages leading to high mortality rates.
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Affiliation(s)
- Victoria J. Grille
- Department of General Surgery, Hackensack Meridian Health School of Medicine at Seton Hall University, Nutley, NJ, USA
| | - Stuart Campbell
- Department of General Surgery, Hackensack Meridian Health School of Medicine at Seton Hall University, Nutley, NJ, USA
| | - John F. Gibbs
- Department of General Surgery, Hackensack Meridian Health School of Medicine at Seton Hall University, Nutley, NJ, USA
- Department of Surgical Oncology, Hackensack Meridian Health School of Medicine at Seton Hall University, Nutley, NJ, USA
| | - Thomas L. Bauer
- Department of General Surgery, Hackensack Meridian Health School of Medicine at Seton Hall University, Nutley, NJ, USA
- Department of Surgery, Jersey Shore University Medical Center, Neptune, NJ, USA
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19
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Mortada WI, Awadalla A, Khater S, Ahmed A, Hamam ET, El-Zayat M, Shokeir AA. Copper and zinc levels in plasma and cancerous tissues and their relation with expression of VEGF and HIF-1 in the pathogenesis of muscle invasive urothelial bladder cancer: a case-controlled clinical study. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:15835-15841. [PMID: 32095963 DOI: 10.1007/s11356-020-08113-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 02/14/2020] [Indexed: 06/10/2023]
Abstract
To evaluate Cu and Zn levels in bladder cancer (BC) patients and their relationship with expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1). Plasma levels of Cu and Zn were determined in 66 transitional bladder cell carcinoma patients (BC group) and 60 matched controls. The concentration of Cu and Zn as well as the expressions of both VEGF and HIF-1 were also estimated in cancerous and non-cancerous bladder tissues in the BC group. The results showed that plasma Cu and Cu/Zn ratio were significantly higher in BC group when compared with the control group. In contrast, the plasma Zn in BC group was significantly lower than in the controls. Comparing levels of Cu and Zn in cancerous and non-cancerous bladder tissues among the BC group indicated a significantly higher Cu levels in the cancerous tissues, while Zn levels was significantly lower. There were higher expressions of both VEGF and HIF-1 in the cancerous samples. Moreover, the Cu concentration in cancerous tissues was significantly correlated with expressions of VEGF and HIF-1. Logistic regression analysis revealed that the increase in plasma Cu/Zn ratio and plasma Cu and the decrease in plasma Zn may be risk factors for development of bladder cancer. We concluded that alteration of plasma and bladder tissue levels of both Cu and Zn is correlated with pathogenesis of bladder cancer. The increase in Cu level in cancerous tissues of BC group has an important role in angiogenesis in bladder cancer cells.
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Affiliation(s)
- Wael I Mortada
- Clinical Chemistry Laboratory, Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt.
| | - Amira Awadalla
- Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt
| | - Sherry Khater
- Pathology Laboratory, Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt
| | - Asmaa Ahmed
- Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt
| | - Eman T Hamam
- Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt
| | - Mustafa El-Zayat
- Unit of Genetic Engineering and Biotechnology, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt
| | - Ahmed A Shokeir
- Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt
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20
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Abstract
Esophageal squamous cell carcinoma and adenocarcinoma account for 95% of all esophageal malignancies. The rates of esophageal adenocarcinoma have increased in Western countries, making it the predominant type of esophageal cancer. Treatment of both types of cancer has transformed to a more minimally invasive approach, with endoscopic methods being used for superficial cancers and more frequent use of video-assisted and laparoscopic modalities for locally advanced tumors. The current National Comprehensive Cancer Network guidelines advocate a trimodal approach to treatment, with neoadjuvant chemoradiation and surgery for locally advanced cancers.
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Affiliation(s)
- Saba Kurtom
- Department of Surgery, Virginia Commonwealth University, West Hospital, 1200 East Broad Street, Box 980135, Richmond, VA 23298, USA
| | - Brian J Kaplan
- Department of Surgery, Division of Surgical Oncology, West Hospital, Virginia Commonwealth University, 1200 East Broad Street, Box 980011, Richmond, VA 23298, USA.
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21
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Han B, Wang X. Semiparametric estimation for the non-mixture cure model in case-cohort and nested case-control studies. Comput Stat Data Anal 2020. [DOI: 10.1016/j.csda.2019.106874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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22
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Fong LY, Taccioli C, Palamarchuk A, Tagliazucchi GM, Jing R, Smalley KJ, Fan S, Altemus J, Fiehn O, Huebner K, Farber JL, Croce CM. Abrogation of esophageal carcinoma development in miR-31 knockout rats. Proc Natl Acad Sci U S A 2020; 117:6075-6085. [PMID: 32123074 PMCID: PMC7084137 DOI: 10.1073/pnas.1920333117] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
MicroRNA-31 (miR-31) is overexpressed in esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary Zn deficiency and inflammation. In a Zn deficiency-promoted rat ESCC model with miR-31 up-regulation, cancer-associated inflammation, and a high ESCC burden following N-nitrosomethylbenzylamine (NMBA) exposure, systemic antimiR-31 delivery reduced ESCC incidence from 85 to 45% (P = 0.038) and miR-31 gene knockout abrogated development of ESCC (P = 1 × 10-6). Transcriptomics, genome sequencing, and metabolomics analyses in these Zn-deficient rats revealed the molecular basis of ESCC abrogation by miR-31 knockout. Our identification of EGLN3, a known negative regulator of nuclear factor κB (NF-κB), as a direct target of miR-31 establishes a functional link between oncomiR-31, tumor suppressor target EGLN3, and up-regulated NF-κB-controlled inflammation signaling. Interaction among oncogenic miR-31, EGLN3 down-regulation, and inflammation was also documented in human ESCCs. miR-31 deletion resulted in suppression of miR-31-associated EGLN3/NF-κB-controlled inflammatory pathways. ESCC-free, Zn-deficient miR-31-/- rat esophagus displayed no genome instability and limited metabolic activity changes vs. the pronounced mutational burden and ESCC-associated metabolic changes of Zn-deficient wild-type rats. These results provide conclusive evidence that miR-31 expression is necessary for ESCC development.
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Affiliation(s)
- Louise Y Fong
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107;
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107
| | - Cristian Taccioli
- Department of Animal Medicine, Production and Health, University of Padova, 35020 Legnaro (PD), Italy
| | - Alexey Palamarchuk
- Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210
| | | | - Ruiyan Jing
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
| | - Karl J Smalley
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107
| | - Sili Fan
- NIH West Coast Metabolomics Center, UC Davis Genome Center, University of California, Davis, CA 95616
| | - Joseph Altemus
- Office of Animal Resources, Thomas Jefferson University, Philadelphia, PA 19107
| | - Oliver Fiehn
- NIH West Coast Metabolomics Center, UC Davis Genome Center, University of California, Davis, CA 95616
| | - Kay Huebner
- Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210
| | - John L Farber
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
| | - Carlo M Croce
- Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;
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Ding J, Jin Z, Yang X, Lou J, Shan W, Hu Y, Du Q, Liao Q, Xu J, Xie R. Plasma membrane Ca 2+-permeable channels and sodium/calcium exchangers in tumorigenesis and tumor development of the upper gastrointestinal tract. Cancer Lett 2020; 475:14-21. [PMID: 32004573 DOI: 10.1016/j.canlet.2020.01.026] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 12/30/2019] [Accepted: 01/23/2020] [Indexed: 12/17/2022]
Abstract
The upper gastrointestinal (GI) tumors are multifactorial diseases associated with a combination of oncogenes and environmental factors. Currently, surgery, chemotherapy, radiotherapy and immunotherapy are relatively effective treatment options for the patients with these tumors. However, the asymptomatic phenotype of these tumors during the early stages poses as a significant limiting factor to diagnosis and often renders treatments ineffective. Therefore, new early diagnosis and effective therapy for upper GI tumors are urgently needed. Ca2+ is a pivotal intracellular second messenger and plays a crucial role in living cells by regulating several processes from cell division to death. The aberrant Ca2+ homeostasis is related to many human pathological conditions and diseases, including cancer, and thus the changes in the expression and function of plasma membrane Ca2+ permeable channels and sodium/calcium exchangers are frequently described in tumorigenesis and tumor development of the upper GI tract, including voltage-gated Ca2+ channels (VGCC), transient receptor potential (TRP) channels, store-operated channels (SOC) and Na+/Ca2+ exchanger (NCX). This review will summarize the current knowledge about plasma membrane Ca2+ permeable channels and sodium/calcium exchangers in the upper GI tumors and provide a synopsis of recent advancements on the role and involvement of these channels in upper GI tumors as well as a discussion of the possible strategies to target these channels and exchangers for diagnosis and therapy of the upper GI tumors.
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Affiliation(s)
- JianHong Ding
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, PR China
| | - Zhe Jin
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, PR China
| | - Xiaoxu Yang
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, PR China
| | - Jun Lou
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, PR China
| | - Weixi Shan
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, PR China
| | - Yanxia Hu
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, PR China
| | - Qian Du
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, PR China
| | - Qiushi Liao
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, PR China
| | - Jingyu Xu
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, PR China.
| | - Rui Xie
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, PR China.
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24
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Pennathur A, Godfrey TE, Luketich JD. The Molecular Biologic Basis of Esophageal and Gastric Cancers. Surg Clin North Am 2019; 99:403-418. [PMID: 31047032 DOI: 10.1016/j.suc.2019.02.010] [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] [Indexed: 12/20/2022]
Abstract
Esophageal cancer and gastric cancer are leading causes of cancer-related mortality worldwide. In this article, the authors discuss the molecular biology of esophageal and gastric cancer with a focus on esophageal adenocarcinoma. They review data from The Cancer Genome Atlas project and advances in the molecular stratification and classification of esophageal carcinoma and gastric cancer. They also summarize advances in microRNA, molecular staging, gene expression profiling, tumor microenvironment, and detection of circulating tumor DNA. Finally, the authors summarize some of the implications of understanding the molecular basis of esophageal cancer and future directions in the management of esophageal cancer.
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Affiliation(s)
- Arjun Pennathur
- Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, The University of Pittsburgh School of Medicine, University of Pittsburgh, 200 Lothrop St. Suite C-800, Pittsburgh, PA 15213, USA.
| | - Tony E Godfrey
- Department of Surgery, Boston University School of Medicine, 700 Albany St, Boston, MA 02118, USA
| | - James D Luketich
- Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, The University of Pittsburgh School of Medicine, University of Pittsburgh, 200 Lothrop St. Suite C-800, Pittsburgh, PA 15213, USA
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25
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Vaden RM, Guillen KP, Salvant JM, Santiago CB, Gibbons JB, Pathi SS, Arunachalam S, Sigman MS, Looper RE, Welm BE. A Cancer-Selective Zinc Ionophore Inspired by the Natural Product Naamidine A. ACS Chem Biol 2019; 14:106-117. [PMID: 30571086 DOI: 10.1021/acschembio.8b00977] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
We present data demonstrating the natural product mimic, zinaamidole A (ZNA), is a modulator of metal ion homeostasis causing cancer-selective cell death by specifically inducing cellular Zn2+-uptake in transformed cells. ZNA's cancer selectivity was evaluated using metastatic, patient-derived breast cancer cells, established human breast cancer cell lines, and three-dimensional organoid models derived from normal and transformed mouse mammary glands. Structural analysis of ZNA demonstrated that the compound interacts with zinc through the N2-acyl-2-aminoimidazole core. Combination treatment with ZnSO4 strongly potentiated ZNA's cancer-specific cell death mechanism, an effect that was not observed with other transition metals. We show that Zn2+-dyshomeostasis induced by ZNA is unique and markedly more selective than other known Zn2+-interacting compounds such as clioquinol. The in vivo bioactivity of ZNA was also assessed and revealed that tumor-bearing mice treated with ZNA had improved survival outcomes. Collectively, these data demonstrate that the N2-acyl-2-aminoimidazole core of ZNA represents a powerful chemotype to induce cell death in cancer cells concurrently with a disruption in zinc homeostasis.
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Affiliation(s)
- Rachel M. Vaden
- Department of Chemistry, University of Utah, 315 S 1400 E, Salt Lake City, Utah 84112, United States
| | | | - Justin M. Salvant
- Department of Chemistry, University of Utah, 315 S 1400 E, Salt Lake City, Utah 84112, United States
| | - Celine B. Santiago
- Department of Chemistry, University of Utah, 315 S 1400 E, Salt Lake City, Utah 84112, United States
| | - Joseph B. Gibbons
- Department of Chemistry, University of Utah, 315 S 1400 E, Salt Lake City, Utah 84112, United States
| | | | | | - Matthew S. Sigman
- Department of Chemistry, University of Utah, 315 S 1400 E, Salt Lake City, Utah 84112, United States
| | - Ryan E. Looper
- Department of Chemistry, University of Utah, 315 S 1400 E, Salt Lake City, Utah 84112, United States
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26
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Reichenbach ZW, Murray MG, Saxena R, Farkas D, Karassik EG, Klochkova A, Patel K, Tice C, Hall TM, Gang J, Parkman HP, Ward SJ, Tétreault MP, Whelan KA. Clinical and translational advances in esophageal squamous cell carcinoma. Adv Cancer Res 2019; 144:95-135. [PMID: 31349905 DOI: 10.1016/bs.acr.2019.05.004] [Citation(s) in RCA: 142] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) is among the most deadly forms of human malignancy characterized by late stage diagnosis, metastasis, therapy resistance and frequent recurrence. Clinical management of ESCC remains challenging and the disease presently lacks approved targeted therapeutics. However, emerging data from recent clinical and translational investigations hold great promise for future progress toward improving patient outcomes in this deadly disease. Here, we review current clinical perspectives in ESCC epidemiology, pathophysiology, and clinical care, highlighting recent advances with potential to impact ESCC prevention, diagnosis and management. We further provide an overview of recent translational investigations contributing to our understanding of the molecular mechanisms underlying ESCC development, progression and therapy response, including insights gained from genetic studies and various murine model systems. Finally, we discuss future perspectives in the clinical and translational realms, along with remaining hurdles that must be overcome to eradicate ESCC.
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Affiliation(s)
- Zachary Wilmer Reichenbach
- Department of Medicine, Gastroenterology Section, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States; Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Mary Grace Murray
- Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Reshu Saxena
- Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Daniel Farkas
- Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
| | - Erika G Karassik
- Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Alena Klochkova
- Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Kishan Patel
- Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Caitlin Tice
- Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
| | - Timothy M Hall
- Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Julie Gang
- Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Henry P Parkman
- Department of Medicine, Gastroenterology Section, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Sarah J Ward
- Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States; Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Marie-Pier Tétreault
- Department of Medicine, Gastroenterology and Hepatology Division, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
| | - Kelly A Whelan
- Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States; Department of Pathology & Laboratory Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States.
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27
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Xie B, Lin J, Sui K, Huang Z, Chen Z, Hang W. Differential diagnosis of multielements in cancerous and non-cancerous esophageal tissues. Talanta 2018; 196:585-591. [PMID: 30683409 DOI: 10.1016/j.talanta.2018.12.061] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 12/05/2018] [Accepted: 12/21/2018] [Indexed: 12/31/2022]
Abstract
It is known that variations in the concentrations of certain elements in humans may be an indication of cancers. In this work, a method for the quantitative analysis of 22 elements in non-tumor and esophageal squamous cell carcinoma (ESCC) tissues from the same individual is reported. Based on the optimized platform combined with multivariate analysis, diagnostic models of ESCC were established using principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), showing excellent classification of cancerous and non-cancerous group by metallomic profiling. Elemental concentrations of 10 elements (Mn, Se, Cu, Ti, Mg, Fe, Co, Zn, Sr, Ca) showed significant difference (p < 0.001) in tumor and non-tumor tissues, in which Mn, Se, Cu and Ti are the top 4 elements of statistical significance and a shift towards higher concentration levels has also been observed in the tumor samples. These results confirm the considerable potential of elemental studies for biomedical purposes. To our knowledge, previous studies on elemental concentration in esophageal cancer were performed in serum or plasma levels; and this is the first study to evaluate the association of tissue elemental concentrations with ESCC.
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Affiliation(s)
- Binbin Xie
- Department of Chemistry and the MOE Key Lab of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005, Fujian, China
| | - Jianqing Lin
- Department of Surgical Oncology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China
| | - Ke Sui
- Department of Chemistry and the MOE Key Lab of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005, Fujian, China
| | - Zhijun Huang
- Department of Surgical Oncology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China
| | - Zhiyao Chen
- Department of Surgical Oncology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China.
| | - Wei Hang
- Department of Chemistry and the MOE Key Lab of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005, Fujian, China.
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28
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Jin J, Guo T, Guo Y, Liu J, Qu F, He Y. Methylation‑associated silencing of miR‑128 promotes the development of esophageal cancer by targeting COX‑2 in areas with a high incidence of esophageal cancer. Int J Oncol 2018; 54:644-654. [PMID: 30535495 DOI: 10.3892/ijo.2018.4653] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 11/05/2018] [Indexed: 01/10/2023] Open
Abstract
Esophageal cancer is one of the most common cancer types in the world, with a widely varying incidence between different regions. Zinc deficiency (ZD) is very common in high‑risk areas for esophageal cancer. Dietary ZD is reported to be associated with esophageal squamous cell carcinoma (ESCC). In the current study, the effects of ZD on tumorigenesis and expression of inflammatory factors were investigated in mice. It was identified that a ZD diet advanced ESCC and increased the expression of cyclooxygenase‑2 (COX‑2) prior to the occurrence of ESCC in mice. ZD significantly enhanced DNA methyltransferase (DNMT) activity and increased the expression of DNMT1 and DNMT3B. Furthermore, the expression of miR‑128 was downregulated by methylation, and COX‑2, a direct target of miR‑128, was upregulated with the reduction in miR‑128. Upregulation of miR‑128 inhibited the cell cycle, proliferation and metastasis, and the expression of COX‑2, cyclin D1 and retinoblastoma protein (Rb). Furthermore, the relative expression level of miR‑128 was negatively associated with COX‑2 in ESCC tissues. Collectively, these findings indicate that methylation‑associated silencing of miR‑128 promotes the development of esophageal cancer through upregulation of the expression of cyclin D1 and Rb by targeting COX‑2 in ZD regions with a high incidence of esophageal cancer.
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Affiliation(s)
- Jing Jin
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Tiantian Guo
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Yongdong Guo
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Jianghui Liu
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Feng Qu
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Yutong He
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
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29
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Fong LY, Jing R, Smalley KJ, Wang ZX, Taccioli C, Fan S, Chen H, Alder H, Huebner K, Farber JL, Fiehn O, Croce CM. Human-like hyperplastic prostate with low ZIP1 induced solely by Zn deficiency in rats. Proc Natl Acad Sci U S A 2018; 115:E11091-E11100. [PMID: 30397150 PMCID: PMC6255182 DOI: 10.1073/pnas.1813956115] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Prostate cancer is a leading cause of cancer death in men over 50 years of age, and there is a characteristic marked decrease in Zn content in the malignant prostate cells. The cause and consequences of this loss have thus far been unknown. We found that in middle-aged rats a Zn-deficient diet reduces prostatic Zn levels (P = 0.025), increases cellular proliferation, and induces an inflammatory phenotype with COX-2 overexpression. This hyperplastic/inflammatory prostate has a human prostate cancer-like microRNA profile, with up-regulation of the Zn-homeostasis-regulating miR-183-96-182 cluster (fold change = 1.41-2.38; P = 0.029-0.0003) and down-regulation of the Zn importer ZIP1 (target of miR-182), leading to a reduction of prostatic Zn. This inverse relationship between miR-182 and ZIP1 also occurs in human prostate cancer tissue, which is known for Zn loss. The discovery that the Zn-depleted middle-aged rat prostate has a metabolic phenotype resembling that of human prostate cancer, with a 10-fold down-regulation of citric acid (P = 0.0003), links citrate reduction directly to prostatic Zn loss, providing the underlying mechanism linking dietary Zn deficiency with miR-183-96-182 overexpression, ZIP1 down-regulation, prostatic Zn loss, and the resultant citrate down-regulation, changes mimicking features of human prostate cancer. Thus, dietary Zn deficiency during rat middle age produces changes that mimic those of human prostate carcinoma and may increase the risk for prostate cancer, supporting the need for assessment of Zn supplementation in its prevention.
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Affiliation(s)
- Louise Y Fong
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107;
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107
| | - Ruiyan Jing
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
| | - Karl J Smalley
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107
| | - Zi-Xuan Wang
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
| | - Cristian Taccioli
- Department of Animal Medicine, Health and Production, University of Padova, 35122 Padova PD, Italy
| | - Sili Fan
- National Institutes of Health West Coast Metabolomics Center, University of California Davis Genome Center, University of California, Davis, CA 95616
| | - Hongping Chen
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107
| | - Hansjuerg Alder
- Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210
- The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210
| | - Kay Huebner
- Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210
- The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210
| | - John L Farber
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
| | - Oliver Fiehn
- National Institutes of Health West Coast Metabolomics Center, University of California Davis Genome Center, University of California, Davis, CA 95616
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
| | - Carlo M Croce
- Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210;
- The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210
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30
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Hashemian M, Murphy G, Etemadi A, Poustchi H, Sharafkhah M, Kamangar F, Pourshams A, Malekshah AF, Khoshnia M, Gharavi A, Hekmatdoost A, Brennan PJ, Boffetta P, Dawsey SM, Abnet CC, Malekzadeh R. Nut consumption and the risk of oesophageal squamous cell carcinoma in the Golestan Cohort Study. Br J Cancer 2018; 119:176-181. [PMID: 29950612 PMCID: PMC6048068 DOI: 10.1038/s41416-018-0148-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Revised: 03/21/2018] [Accepted: 05/23/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Nut consumption has been inversely associated with gastric cancer incidence in US-based studies, but not with oesophageal cancer. However, there is aetiologic heterogeneity, among oesophageal squamous cell carcinoma (ESCC) cases in low-risk vs. high-risk populations. The objective of this study was to evaluate the association between nut consumption and risk of ESCC in a high-risk population. METHODS The Golestan Cohort Study enroled 50,045 participants in Northeastern Iran, between 2004 and 2008. Intake of peanuts, walnuts and mixed nuts (including seeds) were assessed using a validated food frequency questionnaire at baseline. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals for subsequent ESCC adjusted for potential confounders. Non-consumers of nuts were used as the reference category and the consumers were categorised into tertiles. RESULTS We accrued 280 incident ESCC cases during 337,983 person-years of follow up. Individuals in the highest tertiles of total nut consumption, and mixed nut consumption were significantly associated with lower risk of developing ESCC compared to non-consumers (HR = 0.60, 95% CI = 0.39-0.93, p-trend = 0.02, and HR = 0.52, 95% CI = 0.32-0.84, p trend = 0.002, respectively). CONCLUSIONS We found a statistically significant inverse association between total nut consumption and the risk of ESCC in this high-risk population.
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Affiliation(s)
- Maryam Hashemian
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
- Department of Nutrition and Biochemistry, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Gwen Murphy
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Arash Etemadi
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Sharafkhah
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farin Kamangar
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- School of Computer, Mathematical, and Natural Sciences, Morgan State University, Morgan State University, Baltimore, MD, USA
| | - Akram Pourshams
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Akbar Fazeltabar Malekshah
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Khoshnia
- Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Abdolsamad Gharavi
- Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Paul J Brennan
- International Agency for Research on Cancer, Lyon, France
| | - Paolo Boffetta
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Sanford M Dawsey
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Christian C Abnet
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
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31
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Fong LY, Farber JL, Croce CM. Zinc intake, microRNA dysregulation, and esophageal cancer. Aging (Albany NY) 2018; 8:1161-2. [PMID: 27280381 PMCID: PMC4931822 DOI: 10.18632/aging.100978] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 06/08/2016] [Indexed: 11/25/2022]
Affiliation(s)
- Louise Y Fong
- Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - John L Farber
- Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Carlo M Croce
- Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
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32
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Hashemian M, Murphy G, Etemadi A, Poustchi H, Brockman JD, Kamangar F, Pourshams A, Khoshnia M, Gharavi A, Dawsey SM, Brennan PJ, Boffetta P, Hekmatdoost A, Malekzadeh R, Abnet CC. Toenail mineral concentration and risk of esophageal squamous cell carcinoma, results from the Golestan Cohort Study. Cancer Med 2017; 6:3052-3059. [PMID: 29125237 PMCID: PMC5727321 DOI: 10.1002/cam4.1247] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 09/13/2017] [Accepted: 10/05/2017] [Indexed: 12/18/2022] Open
Abstract
Studies conducted in China linked selenium deficiency to higher risk of esophageal squamous cell carcinoma (ESCC), but this has not been widely tested outside that selenium-deficient region. The aim of this study was to investigate the association between selenium and other mineral concentrations in toenails and risk of ESCC in a region with high incidence rates. In this nested case-control study, we identified 222 cases of ESCC from the Golestan Cohort Study, Iran, which has followed up 50,045 participants since enrollment (2004-2008). We randomly selected one control for each case matched by age and sex, using incidence density sampling. We used toenail samples collected at baseline to measure the concentration of selenium, zinc, chromium, mercury, and scandium using instrumental neutron activation analysis. Multivariate adjusted logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals. Median nail selenium, zinc, chromium, and mercury levels were 1.01, 74.59, 0.77, and 0.018 μg/g in cases and 1.02, 75.71, 0.71, and 0.023 μg/g in controls, respectively. The adjusted odds ratios comparing each fourth quartile of mineral status versus the first quartile were as follows: selenium = 0.78 (95% CI, 0.41-1.49); zinc=0.80 (95% CI, 0.42-1.53); chromium = 0.91 (95% CI, 0.46-1.80); and mercury=0.61 (95% CI, 0.27-1.38), and all trend tests were non-significant. The nail selenium concentration in our controls reflects relatively high selenium status. No evidence of association between selenium or chromium concentrations in toenails and the risk of ESCC was detected in this population.
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Affiliation(s)
- Maryam Hashemian
- Digestive Oncology Research CenterDigestive Diseases Research InstituteTehran University of Medical SciencesTehranIran
- Metabolic Epidemiology BranchDivision of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaMaryland
- Departments of Nutrition and BiochemistryFaculty of MedicineSabzevar University of Medical SciencesSabzevarIran
| | - Gwen Murphy
- Metabolic Epidemiology BranchDivision of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaMaryland
| | - Arash Etemadi
- Digestive Oncology Research CenterDigestive Diseases Research InstituteTehran University of Medical SciencesTehranIran
- Metabolic Epidemiology BranchDivision of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaMaryland
| | - Hossein Poustchi
- Digestive Oncology Research CenterDigestive Diseases Research InstituteTehran University of Medical SciencesTehranIran
- Liver and Pancreatobiliary Diseases Research CenterDigestive Diseases Research InstituteTehran University of Medical SciencesTehranIran
| | - John D. Brockman
- Research Reactor CentreUniversity of Missouri‐ColumbiaColumbiaMissouri
| | - Farin Kamangar
- Digestive Disease Research CenterDigestive Diseases Research InstituteTehran University of Medical SciencesTehranIran
- School of Computer, Mathematical, and Natural SciencesMorgan State UniversityMorgan State UniversityBaltimoreMaryland
| | - Akram Pourshams
- Liver and Pancreatobiliary Diseases Research CenterDigestive Diseases Research InstituteTehran University of Medical SciencesTehranIran
| | - Masoud Khoshnia
- Digestive Disease Research CenterDigestive Diseases Research InstituteTehran University of Medical SciencesTehranIran
- Golestan Research Center of Gastroenterology and HepatologyGolestan University of Medical SciencesGorganIran
| | - Abdolsamad Gharavi
- Digestive Disease Research CenterDigestive Diseases Research InstituteTehran University of Medical SciencesTehranIran
- Golestan Research Center of Gastroenterology and HepatologyGolestan University of Medical SciencesGorganIran
| | - Sanford M. Dawsey
- Metabolic Epidemiology BranchDivision of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaMaryland
| | | | - Paolo. Boffetta
- Tisch Cancer InstituteIcahn School of Medicine at Mount SinaiNew YorkNew York
| | - Azita Hekmatdoost
- Departments of Clinical Nutrition and DieteticsFaculty of Nutrition and Food TechnologyNational Nutrition and Food Technology Research InstituteShahid Beheshti University of Medical SciencesTehranIran
| | - Reza Malekzadeh
- Digestive Oncology Research CenterDigestive Diseases Research InstituteTehran University of Medical SciencesTehranIran
- Digestive Disease Research CenterDigestive Diseases Research InstituteTehran University of Medical SciencesTehranIran
| | - Christian C. Abnet
- Metabolic Epidemiology BranchDivision of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaMaryland
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Fong LY, Taccioli C, Jing R, Smalley KJ, Alder H, Jiang Y, Fadda P, Farber JL, Croce CM. MicroRNA dysregulation and esophageal cancer development depend on the extent of zinc dietary deficiency. Oncotarget 2017; 7:10723-38. [PMID: 26918602 PMCID: PMC4905434 DOI: 10.18632/oncotarget.7561] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Accepted: 02/08/2016] [Indexed: 12/21/2022] Open
Abstract
Zinc deficiency (ZD) increases the risk of esophageal squamous cell carcinoma (ESCC), and marginal ZD is prevalent in humans. In rats, marked-ZD (3 mg Zn/kg diet) induces a proliferative esophagus with a 5-microRNA signature (miR-31, -223, -21, -146b, -146a) and promotes ESCC. Here we report that moderate and mild-ZD (6 and 12 mg Zn/kg diet) also induced esophageal hyperplasia, albeit less pronounced than induced by marked-ZD, with a 2-microRNA signature (miR-31, -146a). On exposure to an environmental carcinogen, ∼16% of moderate/mild-ZD rats developed ESCC, a cancer incidence significantly greater than for Zn-sufficient rats (0%) (P ≤ 0.05), but lower than marked-ZD rats (68%) (P < 0.001). Importantly, the high ESCC, marked-ZD esophagus had a 15-microRNA signature, resembling the human ESCC miRNAome, with miR-223, miR-21, and miR-31 as the top-up-regulated species. This signature discriminated it from the low ESCC, moderate/mild-ZD esophagus, with a 2-microRNA signature (miR-31, miR-223). Additionally, Fbxw7, Pdcd4, and Stk40 (tumor-suppressor targets of miR-223, -21, and -31) were downregulated in marked-ZD cohort. Bioinformatics analysis predicted functional relationships of the 3 tumor-suppressors with other cancer-related genes. Thus, microRNA dysregulation and ESCC progression depend on the extent of dietary Zn deficiency. Our findings suggest that even moderate ZD may promote esophageal cancer and dietary Zn has preventive properties against ESCC. Additionally, the deficiency-associated miR-223, miR-21, and miR-31 may be useful therapeutic targets in ESCC.
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Affiliation(s)
- Louise Y Fong
- Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.,Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
| | - Cristian Taccioli
- Animal Medicine, Production and Health Department, University of Padua, Padua, Italy
| | - Ruiyan Jing
- Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Karl J Smalley
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
| | - Hansjuerg Alder
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Yubao Jiang
- Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Paolo Fadda
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - John L Farber
- Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Carlo M Croce
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
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Yin J, Tang W, Long T, Pan H, Liu J, Lv L, Liu C, Shi Y, Zhu J, Sun Y, Shao A, Zhou Q, Ren Z, Ding G, Chen S, Liu Y, Yao J, Ding H, Yan Y, Gu H, Qian C, Wang L, Wang Q, Tan L. Association of ALDH3B2 gene polymorphism and risk factors with susceptibility of esophageal squamous cell carcinoma in a Chinese population: a case-control study involving 2,358 subjects. Oncotarget 2017; 8:110153-110165. [PMID: 29299137 PMCID: PMC5746372 DOI: 10.18632/oncotarget.22656] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Accepted: 10/30/2017] [Indexed: 12/11/2022] Open
Abstract
Background Esophageal cancer (EC) is the sixth leading cause of cancer-associated death worldwide. The interaction of environmental risk factors and genetic factors might contribute to the carcinogenesis of EC synergistically. Results All seven single locus polymorphisms of ALDH3B2 were not associated with risk of ESCC as evaluated by allelic, dominant, co-dominant, recessive and Cochran-Armitage trend tests. Stratified analyses showed these SNPs were not correlated with the susceptibility of ESCC according to different age, gender, cigarette smoking and alcohol drinking status. None of the major haplotypes were related with ESCC susceptibility. Materials and Methods We conducted a hospital-based case-control study to evaluate the combined effects of environmental risk factors and the single nucleotide polymorphisms (SNPs) of ALDH3B2 gene on the development of esophageal squamous carcinoma (ESCC). A total of 1043 ESCC cases and 1315 controls were recruited for this study. Seven ALDH3B2 SNPs and four environmental factors were selected as independent variables. ALDH3B2 SNPs were determined by ligation detection reaction method. Conclusions Our study suggested that ALDH3B2 rs34589365, rs3741172, rs4646823, rs78402723, rs7947978, rs866907 and rs9787887 polymorphisms were not implicated with altered susceptibility of ESCC according to different age, gender, cigarette smoking and alcohol drinking status. Yet this conclusion needs to be verified in larger studies among different ethnic populations with validation design, the biological function of these SNPs in carcinogenesis are subject to further investigation.
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Affiliation(s)
- Jun Yin
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China.,Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, 200032, China
| | - Weifeng Tang
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Tao Long
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Huiwen Pan
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Jianchao Liu
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Lu Lv
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Chao Liu
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Yijun Shi
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Jingfeng Zhu
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Yangyong Sun
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Aizhong Shao
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Qiang Zhou
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Zhengbing Ren
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Guowen Ding
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Suocheng Chen
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Yan Liu
- Genesky Biotechnologies Inc., Shanghai, 201315, China
| | - Jun Yao
- Department of Gastroenterology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Hao Ding
- Department of Respirology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Yulan Yan
- Department of Respirology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Haiyong Gu
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China
| | - Cheng Qian
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, 200032, China
| | - Liming Wang
- Cancer Institute, Department of Chemotherapy, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, China
| | - Qun Wang
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, 200032, China
| | - Lijie Tan
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, 200032, China
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35
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Song H, Saito E, Sawada N, Abe SK, Hidaka A, Shimazu T, Yamaji T, Goto A, Iwasaki M, Sasazuki S, Ye W, Inoue M, Tsugane S. Body mass index change during adulthood and risk of oesophageal squamous-cell carcinoma in a Japanese population: the Japan Public Health (JPHC)-based prospective study. Br J Cancer 2017; 117:1715-1722. [PMID: 28949955 PMCID: PMC5729434 DOI: 10.1038/bjc.2017.332] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 08/02/2017] [Accepted: 08/30/2017] [Indexed: 01/11/2023] Open
Abstract
Background: The influence of body mass index (BMI) change during adulthood on the development of oesophageal squamous-cell carcinoma (ESCC) is unknown. Methods: Based on the Japan Public Health Center-based Prospective Study, we enrolled 103 238 participants from 1990 to 1994. Anthropometric data at age 20 years, baseline, and 5- and/or 10-year follow-up surveys were collected by questionnaire. The effect of BMI change between age 20 years and baseline on ESCC risk was estimated by Cox proportional hazards regression models. The updated BMI was taken into account by fitting a simple linear regression model for each individual, where the slope was incorporated into regressions as a time-varying variable. Results: After excluding the first 5 years of observation, we identified 342 newly diagnosed ESCC cases. An increase in BMI during adulthood was linked with a decreased risk of ESCC development, with each 1% increase per 5 years corresponding to a 15% decrease in ESCC risk (95% confidence interval 9–21%). Identical estimates were obtained from time-dependent models. The importance of BMI change was not modified by gender, smoking, or alcohol drinking but confined to participants assessed as non-overweight at baseline. Conclusions: An increase in BMI during adulthood is associated with a lower risk of developing ESCC among non-overweight subjects.
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Affiliation(s)
- Huan Song
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,AXA Department of Health and Human Security, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.,Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Eiko Saito
- AXA Department of Health and Human Security, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.,Epidemiology and Prevention group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan.,Division of Cancer Statistics Integration, Center for Cancer Control & Information Services, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan
| | - Norie Sawada
- Epidemiology and Prevention group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan
| | - Sarah K Abe
- Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Akihisa Hidaka
- Epidemiology and Prevention group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan
| | - Taichi Shimazu
- Epidemiology and Prevention group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan
| | - Taiki Yamaji
- Epidemiology and Prevention group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan
| | - Atsushi Goto
- Epidemiology and Prevention group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan
| | - Motoki Iwasaki
- Epidemiology and Prevention group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan
| | - Shizuka Sasazuki
- Epidemiology and Prevention group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan
| | - Weimin Ye
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Manami Inoue
- AXA Department of Health and Human Security, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.,Epidemiology and Prevention group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan
| | - Shoichiro Tsugane
- Epidemiology and Prevention group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan
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36
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Choi S, Cui C, Luo Y, Kim SH, Ko JK, Huo X, Ma J, Fu LW, Souza RF, Korichneva I, Pan Z. Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1. FASEB J 2017; 32:404-416. [PMID: 28928244 DOI: 10.1096/fj.201700227rrr] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 09/05/2017] [Indexed: 12/15/2022]
Abstract
Zinc, an essential micronutrient, has a cancer preventive role. Zinc deficiency has been shown to contribute to the progression of esophageal cancer. Orai1, a store-operated Ca2+ entry (SOCE) channel, was previously reported to be highly expressed in tumor tissues removed from patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis, and elevation of its expression contributes to both hyperactive intracellular Ca2+ oscillations and fast cell proliferation in human ESCC cells. However, the molecular basis of cancer preventive functions of zinc and its association with Orai1-mediated cell proliferation remains unknown. The present study shows that zinc supplementation significantly inhibits proliferation of ESCC cell lines and that the effect of zinc is reversible with N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine, a specific Zn2+ chelator, whereas nontumorigenic esophageal epithelial cells are significantly less sensitive to zinc treatment. Fluorescence live cell imaging revealed that extracellular Zn2+ exerted rapid inhibitory effects on Orai1-mediated SOCE and on intracellular Ca2+ oscillations in the ESCC cells. Knockdown of Orai1 or expression of Orai1 mutants with compromised zinc binding significantly diminished sensitivity of the cancer cells to zinc treatment in both SOCE and cell proliferation analyses. These data suggest that zinc may inhibit cell proliferation of esophageal cancer cells through Orai1-mediated intracellular Ca2+ oscillations and reveal a possible molecular basis for zinc-induced cancer prevention and Orai1-SOCE signaling pathway in cancer cells.-Choi, S., Cui, C., Luo, Y., Kim, S.-H., Ko, J.-K., Huo, X., Ma, J., Fu, L.-W., Souza, R. F., Korichneva, I., Pan, Z. Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1.
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Affiliation(s)
- Sangyong Choi
- College of Nursing and Health Innovation, The University of Texas at Arlington, Arlington, Texas, USA.,Davis Heart and Lung Research Institute, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Chaochu Cui
- College of Nursing and Health Innovation, The University of Texas at Arlington, Arlington, Texas, USA.,Davis Heart and Lung Research Institute, Ohio State University Wexner Medical Center, Columbus, Ohio, USA.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yanhong Luo
- Davis Heart and Lung Research Institute, Ohio State University Wexner Medical Center, Columbus, Ohio, USA.,Department of Endocrinology, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Sun-Hee Kim
- Davis Heart and Lung Research Institute, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | | | - Xiaofang Huo
- Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas, Texas, USA
| | - Jianjie Ma
- Davis Heart and Lung Research Institute, Ohio State University Wexner Medical Center, Columbus, Ohio, USA.,Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA; and
| | - Li-Wu Fu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Rhonda F Souza
- Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas, Texas, USA
| | - Irina Korichneva
- Department of Pharmacology, University of Picardie Jules Verne, Amiens, France
| | - Zui Pan
- College of Nursing and Health Innovation, The University of Texas at Arlington, Arlington, Texas, USA; .,Davis Heart and Lung Research Institute, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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37
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Hashemian M, Murphy G, Etemadi A, Dawsey SM, Liao LM, Abnet CC. Nut and peanut butter consumption and the risk of esophageal and gastric cancer subtypes. Am J Clin Nutr 2017; 106:858-864. [PMID: 28768652 PMCID: PMC5573026 DOI: 10.3945/ajcn.117.159467] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 06/29/2017] [Indexed: 12/15/2022] Open
Abstract
Background: Nut consumption has been associated with decreased risk of colorectal, endometrial, lung, and pancreatic cancers. Polyphenols, fiber, vitamins, and minerals in nuts may confer this observed protective effect. To our knowledge, no prospective study has evaluated the effect of nut consumption on esophageal and gastric cancers.Objective: The objective was to evaluate the associations between nut and peanut butter consumption and the risk of esophageal and gastric cancers and their different subtypes.Design: In this study we used data from the NIH-AARP Diet and Health Study, which enrolled 566,407 persons who were 50-71 y old at baseline (1995-1996). The median follow-up time was 15.5 y. Intakes of nuts and peanut butter were assessed through the use of a validated food-frequency questionnaire. We used Cox proportional hazard models to estimate HRs and 95% CIs for esophageal and gastric cancers and their subtypes.Results: We identified 966 incident cases of esophageal adenocarcinomas, 323 cases of esophageal squamous cell carcinoma, 698 cases of gastric cardia adenocarcinoma, and 732 cases of gastric noncardia adenocarcinoma. Compared with those who did not consume nuts or peanut butter [lowest category of consumption (C0)], participants in the highest category of nut consumption (C3) had a lower risk of developing gastric noncardia adenocarcinoma [C3 compared with C0, HR: 0.73 (95% CI: 0.57, 0.94)]. This inverse association was also seen for peanut butter consumption [C3 compared with C0, HR: 0.75 (95% CI: 0.60, 0.94)]. We observed no significant associations between the highest and lowest intakes of nuts or peanut butter and the risk of gastric cardia adenocarcinoma, esophageal adenocarcinoma, or esophageal squamous cell carcinoma.Conclusions: Among older American adults, both nut and peanut butter consumption were inversely associated with the risk of gastric noncardia adenocarcinoma. This trial was registered at clinicaltrials.gov as NCT00340015.
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Affiliation(s)
- Maryam Hashemian
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD;,Departments of Nutrition and Biochemistry, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran; and,Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Gwen Murphy
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
| | - Arash Etemadi
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
| | - Sanford M Dawsey
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
| | - Linda M Liao
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
| | - Christian C Abnet
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD;
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38
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Fong LY, Jing R, Smalley KJ, Taccioli C, Fahrmann J, Barupal DK, Alder H, Farber JL, Fiehn O, Croce CM. Integration of metabolomics, transcriptomics, and microRNA expression profiling reveals a miR-143-HK2-glucose network underlying zinc-deficiency-associated esophageal neoplasia. Oncotarget 2017; 8:81910-81925. [PMID: 29137232 PMCID: PMC5669858 DOI: 10.18632/oncotarget.18434] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Accepted: 05/29/2017] [Indexed: 01/01/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) in humans is a deadly disease associated with dietary zinc (Zn)-deficiency. In the rat esophagus, Zn-deficiency induces cell proliferation, alters mRNA and microRNA gene expression, and promotes ESCC. We investigated whether Zn-deficiency alters cell metabolism by evaluating metabolomic profiles of esophageal epithelia from Zn-deficient and replenished rats vs sufficient rats, using untargeted gas chromatography time-of-flight mass spectrometry (n = 8/group). The Zn-deficient proliferative esophagus exhibits a distinct metabolic profile with glucose down 153-fold and lactic acid up 1.7-fold (P < 0.0001), indicating aerobic glycolysis (the “Warburg effect”), a hallmark of cancer cells. Zn-replenishment rapidly increases glucose content, restores deregulated metabolites to control levels, and reverses the hyperplastic phenotype. Integration of metabolomics and our reported transcriptomic data for this tissue unveils a link between glucose down-regulation and overexpression of HK2, an enzyme that catalyzes the first step of glycolysis and is overexpressed in cancer cells. Searching our published microRNA profile, we find that the tumor-suppressor miR-143, a negative regulator of HK2, is down-regulated in Zn-deficient esophagus. Using in situ hybridization and immunohistochemical analysis, the inverse correlation between miR-143 down-regulation and HK2 overexpression is documented in hyperplastic Zn-deficient esophagus, archived ESCC-bearing Zn-deficient esophagus, and human ESCC tissues. Thus, to sustain uncontrolled cell proliferation, Zn-deficiency reprograms glucose metabolism by modulating expression of miR-143 and its target HK2. Our work provides new insight into critical roles of Zn in ESCC development and prevention.
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Affiliation(s)
- Louise Y Fong
- Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.,Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.,Center for Molecular Carcinogenesis, Thomas Jefferson University, Philadelphia, PA, USA
| | - Ruiyan Jing
- Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Karl J Smalley
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
| | - Cristian Taccioli
- Animal Medicine, Production and Health Department, University of Padua, Padua, Italy
| | - Johannes Fahrmann
- University of California, Davis, West Coast Metabolomics Center, Davis, CA, USA
| | - Dinesh K Barupal
- University of California, Davis, West Coast Metabolomics Center, Davis, CA, USA
| | - Hansjuerg Alder
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - John L Farber
- Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Oliver Fiehn
- University of California, Davis, West Coast Metabolomics Center, Davis, CA, USA.,Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Carlo M Croce
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
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39
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Wróbel Ł, Gudyś A, Sikora M. Learning rule sets from survival data. BMC Bioinformatics 2017; 18:285. [PMID: 28558674 PMCID: PMC5450332 DOI: 10.1186/s12859-017-1693-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 05/18/2017] [Indexed: 11/18/2022] Open
Abstract
Background Survival analysis is an important element of reasoning from data. Applied in a number of fields, it has become particularly useful in medicine to estimate the survival rate of patients on the basis of their condition, examination results, and undergoing treatment. The recent developments in the next generation sequencing open new opportunities in survival study as they allow vast amount of genome-, transcriptome-, and proteome-related features to be investigated. These include single nucleotide and structural variants, expressions of genes and microRNAs, DNA methylation, and many others. Results We present LR-Rules, a new algorithm for rule induction from survival data. It works according to the separate-and-conquer heuristics with a use of log-rank test for establishing rule body. Extensive experiments show LR-Rules to generate models of superior accuracy and comprehensibility. The detailed analysis of rules rendered by the presented algorithm on four medical datasets concerning leukemia as well as breast, lung, and thyroid cancers, reveals the ability to discover true relations between attributes and patients’ survival rate. Two of the case studies incorporate features obtained with a use of high throughput technologies showing the usability of the algorithm in the analysis of bioinformatics data. Conclusions LR-Rules is a viable alternative to existing approaches to survival analysis, particularly when the interpretability of a resulting model is crucial. Presented algorithm may be especially useful when applied on the genomic and proteomic data as it may contribute to the better understanding of the background of diseases and support their treatments. Electronic supplementary material The online version of this article (doi:10.1186/s12859-017-1693-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Łukasz Wróbel
- Institute of Informatics, Silesian Univ. of Technology, Akademicka 16, Gliwice, 44-100, Poland.
| | - Adam Gudyś
- Institute of Informatics, Silesian Univ. of Technology, Akademicka 16, Gliwice, 44-100, Poland
| | - Marek Sikora
- Institute of Innovative Technologies, EMAG, Leopolda 31, Katowice, 40-189, Poland
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40
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Li Q, Jin J, Liu J, Wang L, He Y. Knockdown of Zinc Transporter ZIP5 by RNA Interference Inhibits Esophageal Cancer Growth In Vivo. Oncol Res 2017; 24:205-14. [PMID: 27458102 PMCID: PMC7838672 DOI: 10.3727/096504016x14648701447896] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
We recently found that SLC39A5 (ZIP5), a zinc transporter, is overexpressed in esophageal cancer. Downregulation of ZIP5 inhibited the proliferation, migration, and invasion of the esophageal cancer cell line KYSE170 in vitro. In this study, we found that downregulation of SLC39A5 (ZIP5) by interference resulted in a significant reduction in esophageal cancer tumor volume and weight in vivo. COX2 (cyclooxygenase 2) expression was decreased and E-cadherin expression was increased in the KYSE170K xenografts, which was caused by the downregulation of ZIP5. However, we did not find that the downregulation of ZIP5 caused a change in the relative expressions of cyclin D1, VEGF (vascular endothelial growth factor), MMP9 (matrix metalloprotein 9), and Bcl-2 (B-cell lymphoma/leukmia-2) mRNA or an alteration in the average level of zinc in the peripheral blood and xenografts in vivo. Collectively, these findings indicate that knocking down ZIP5 by small interfering RNA (siRNA) might be a novel treatment strategy for esophageal cancer with ZIP5 overexpression.
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Affiliation(s)
- Qian Li
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
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Wu Y, Yan M, Li J, Li J, Chen Z, Chen P, Li B, Chen F, Jin T, Chen C. Genetic polymorphisms in TERT are associated with increased risk of esophageal cancer. Oncotarget 2017; 8:10523-10530. [PMID: 28060765 PMCID: PMC5354677 DOI: 10.18632/oncotarget.14451] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Accepted: 12/13/2016] [Indexed: 12/20/2022] Open
Abstract
Single nucleotide polymorphisms (SNPs) in TERT may be associated with susceptibility to esophageal cancer. In this study, we analyzed the association between TERT SNPs and risk of esophageal cancer in 386 esophageal cancer patients and 495 healthy subjects from the Xi'an area of China. Of the four SNPs examined, rs10069690 and rs2242652 were correlated with esophageal cancer risk. Additionally, after adjusting for age and gender, the "Trs10069690Ars2242652", "Trs10069690Grs2242652" haplotypes were associated with an increased risk of esophageal cancer, while the and "Crs10069690Grs2242652" haplotype was associated with a decreased risk of esophageal cancer. These findings suggest that TERT polymorphisms may contribute to the development of esophageal cancer.
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Affiliation(s)
- Yifei Wu
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an, Shaanxi 710069, China
| | - Mengdan Yan
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an, Shaanxi 710069, China
- Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi 710075, China
| | - Jing Li
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an, Shaanxi 710069, China
- Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi 710075, China
| | - Jingjie Li
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an, Shaanxi 710069, China
- Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi 710075, China
| | - Zhengshuai Chen
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an, Shaanxi 710069, China
- Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi 710075, China
| | - Peng Chen
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an, Shaanxi 710069, China
- Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi 710075, China
- Institution of Basic Medical Science, Xi'an Medical University, Xi’an, Shaanxi 710021, China
| | - Bin Li
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an, Shaanxi 710069, China
- Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi 710075, China
| | - Fulin Chen
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an, Shaanxi 710069, China
| | - Tianbo Jin
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an, Shaanxi 710069, China
- Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi 710075, China
| | - Chao Chen
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an, Shaanxi 710069, China
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McCormack VA, Menya D, Munishi MO, Dzamalala C, Gasmelseed N, Leon Roux M, Assefa M, Osano O, Watts M, Mwasamwaja AO, Mmbaga BT, Murphy G, Abnet CC, Dawsey SM, Schüz J. Informing etiologic research priorities for squamous cell esophageal cancer in Africa: A review of setting-specific exposures to known and putative risk factors. Int J Cancer 2017; 140:259-271. [PMID: 27466161 PMCID: PMC5763498 DOI: 10.1002/ijc.30292] [Citation(s) in RCA: 114] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 07/08/2016] [Indexed: 12/30/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in most Eastern and Southern African countries, but its etiology has been understudied to date. To inform its research agenda, we undertook a review to identify, of the ESCC risk factors which have been established or strongly suggested worldwide, those with a high prevalence or high exposure levels in any ESCC-affected African setting and the sources thereof. We found that for almost all ESCC risk factors known to date, including tobacco, alcohol, hot beverage consumption, nitrosamines and both inhaled and ingested PAHs, there is evidence of population groups with raised exposures, the sources of which vary greatly between cultures across the ESCC corridor. Research encompassing these risk factors is warranted and is likely to identify primary prevention strategies.
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Affiliation(s)
- V A McCormack
- Section of Environment and Radiation, International Agency for Research on Cancer (IARC), Lyon, France
| | - D Menya
- School of Public Health, Moi University, Eldoret, Kenya
| | - M O Munishi
- Kilimanjaro Clinical Research Institute, Moshi, Tanzania
| | - C Dzamalala
- College of Medicine, University of Malawi, Blantyre, Malawi
- Malawi Cancer Registry, Malawi
| | - N Gasmelseed
- National Cancer Institute, University of Gezira, Sudan
- Faculty of Science, University of Hafr Al Batin, Saudi Arabia
| | - M Leon Roux
- Section of Environment and Radiation, International Agency for Research on Cancer (IARC), Lyon, France
| | - M Assefa
- Radiotherapy Center, Addis-Ababa-University, Addis Ababa, Ethiopia
| | - O Osano
- School of Environmental Studies, University of Eldoret, Kenya
| | - M Watts
- Inorganic Chemistry, Centre for Environmental Geochemistry, British Geological Survey, Nottingham, United Kingdom
| | - A O Mwasamwaja
- Kilimanjaro Clinical Research Institute, Moshi, Tanzania
- Kilimanjaro Christian Medical Centre, Moshi, Tanzania
| | - B T Mmbaga
- Kilimanjaro Clinical Research Institute, Moshi, Tanzania
- Kilimanjaro Christian Medical Centre, Moshi, Tanzania
| | - G Murphy
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
| | - C C Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
| | - S M Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
| | - J Schüz
- Section of Environment and Radiation, International Agency for Research on Cancer (IARC), Lyon, France
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Pan Z, Choi S, Ouadid-Ahidouch H, Yang JM, Beattie JH, Korichneva I. Zinc transporters and dysregulated channels in cancers. Front Biosci (Landmark Ed) 2017; 22:623-643. [PMID: 27814637 DOI: 10.2741/4507] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
As a nutritionally essential metal ion, zinc (Zn) not only constitutes a structural element for more than 3000 proteins but also plays important regulatory functions in cellular signal transduction. Zn homeostasis is tightly controlled by regulating the flux of Zn across cell membranes through specific transporters, i.e. ZnT and ZIP family proteins. Zn deficiency and malfunction of Zn transporters have been associated with many chronic diseases including cancer. However, the mechanisms underlying Zn regulatory functions in cellular signaling and their impact on the pathogenesis and progression of cancers remain largely unknown. In addition to these acknowledged multifunctions, Zn modulates a wide range of ion channels that in turn may also play an important role in cancer biology. The goal of this review is to propose how zinc deficiency, through modified Zn homeostasis, transporter activity and the putative regulatory function of Zn can influence ion channel activity, and thereby contribute to carcinogenesis and tumorigenesis. This review intends to stimulate interest in, and support for research into the understanding of Zn-modulated channels in cancers, and to search for novel biomarkers facilitating effective clinical stratification of high risk cancer patients as well as improved prevention and therapy in this emerging field.
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Affiliation(s)
- Zui Pan
- The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA,
| | - Sangyong Choi
- Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Halima Ouadid-Ahidouch
- University of Picardie Jules Verne, UFR Sciences, EA 4667, Laboratory of Cell and Molecular Physiology, SFR CAP-SANTE (FED 4231), Amiens, France
| | - Jin-Ming Yang
- Department of Pharmacology, College of Medicine, Penn State University, 500 University Drive Hershey, PA 17033, USA
| | - John H Beattie
- Rowett Institute of Nutrition and Health, University of Aberdeen, Foresterhill, Bucksburn, Aberdeen AB25 2ZD, Scotland, UK
| | - Irina Korichneva
- University of Picardie Jules Verne, UFR Sciences, EA 4667, Laboratory of Cell and Molecular Physiology, SFR CAP-SANTE (FED 4231), Amiens, France
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He Y, Jin J, Wang L, Hu Y, Liang D, Yang H, Liu Y, Shan B. Evaluation of miR-21 and miR-375 as prognostic biomarkers in oesophageal cancer in high-risk areas in China. Clin Exp Metastasis 2016; 34:73-84. [PMID: 27885434 PMCID: PMC5285435 DOI: 10.1007/s10585-016-9828-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Accepted: 10/22/2016] [Indexed: 12/31/2022]
Abstract
MicroRNAs have been associated with prognosis in oesophageal cancer (EC), suggesting that miRNAs could play a role in guiding treatment decisions. The aim of this study was to evaluate the prognostic potential of miRNAs found to be associated with zinc deficiency in a geographical area with a high incidence of EC. miRNAs found to be associated with zinc deficiency were isolated from EC cell lines cultured with various Zn levels. The expression levels of the miRNAs were quantified using qRT-PCR. The potential prognostic value of the selected miRNAs was assessed in a cohort study of 88 patients from an area in China with a high incidence of EC. Correlations between miRNAs and patient characteristics were assessed using χ2 statistical tests or Fisher's exact test. A Cox proportional hazards model was used to assess the correlations between miRNAs and overall survival (OS). Forest plots were performed to evaluate the prognostic impact of the miRNAs examined in the present study in the Asian population. The expression levels of miR-21, miR-31, miR-93 and miR-375 were different when Zn levels were varied in EC cell lines, but only miR-21 and miR-375 were associated with patient characteristics and prognosis in patients with EC from an area of China with a high incidence of EC. The patients expressing high levels of miR-21 had poor OS (HR 2.15, 95% CI 1.16-3.97), whereas those with high levels of miR-375 had improved OS (HR 0.47, 95% CI 0.26-0.87).The patients with both a high level of miR-375 and a low level of miR-21 had significantly better outcomes. Forest plots based on an analysis of this Asian population indicated that a high level of miR-21 significantly predicted a shortened OS (HR 1.83, 95% CI 1.42-2.37), whereas a high level of miR-375 was significantly correlated with increased survival (HR 0.56, 95% CI 0.43-0.73). MiR-21 and miR-375 could be used as prognostic biomarkers in areas with a high incidence of EC, and combining these markers may results in a better effect.
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Affiliation(s)
- Yutong He
- Cancer Institute, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, 050011, China
| | - Jing Jin
- Cancer Institute, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, 050011, China
| | - LiQun Wang
- Cancer Institute, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, 050011, China
| | - Yuejiao Hu
- Hospital Medical Insurance Department, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, China
| | - Di Liang
- Cancer Institute, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, 050011, China
| | - Huichai Yang
- Pathology Department, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, China
| | - Yueping Liu
- Pathology Department, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, China
| | - Baoen Shan
- Cancer Institute, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, 050011, China.
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Sun J, Shen R, Schrock MS, Liu J, Pan X, Quimby D, Zanesi N, Druck T, Fong LY, Huebner K. Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation. Cancer Med 2016; 5:2032-42. [PMID: 27185213 PMCID: PMC4873604 DOI: 10.1002/cam4.768] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Revised: 04/12/2016] [Accepted: 04/21/2016] [Indexed: 11/10/2022] Open
Abstract
Inadequate dietary Zn consumption increases susceptibility to esophageal and other cancers in humans and model organisms. Since Zn supplementation can prevent cancers in rodent squamous cell carcinoma (SCC) models, we were interested in determining if it could have a preventive effect in a rodent skin cancer model, as a preclinical basis for considering a role for Zn in prevention of human nonmelanoma skin cancers, the most frequent cancers in humans. We used the 7,12-dimethyl benzanthracene carcinogen/phorbol myristate acetate tumor promoter treatment method to induce skin tumors in Zn-sufficient wild-type and Fhit (human or mouse protein) knockout mice. Fhit protein expression is lost in >50% of human cancers, including skin SCCs, and Fhit-deficient mice show increased sensitivity to carcinogen induction of tumors. We hypothesized that: (1) the skin cancer burdens would be reduced by Zn supplementation; (2) Fhit(-/-) (Fhit, murine fragile histidine triad gene) mice would show increased susceptibility to skin tumor induction versus wild-type mice. 30 weeks after initiating treatment, the tumor burden was increased ~2-fold in Fhit(-/-) versus wild-type mice (16.2 versus 7.6 tumors, P < 0.001); Zn supplementation significantly reduced tumor burdens in Fhit(-/-) mice (males and females combined, 16.2 unsupplemented versus 10.3 supplemented, P = 0.001). Most importantly, the SCC burden was reduced after Zn supplementation in both strains and genders of mice, most significantly in the wild-type males (P = 0.035). Although the mechanism(s) of action of Zn supplementation in skin tumor prevention is not known in detail, the Zn-supplemented tumors showed evidence of reduced DNA damage and some cohorts showed reduced inflammation scores. The results suggest that mild Zn supplementation should be tested for prevention of skin cancer in high-risk human cohorts.
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Affiliation(s)
- Jin Sun
- Department of Molecular Virology, Immunology and Medical GeneticsThe Ohio State University Comprehensive Cancer CenterColumbusOhio
- Present address: Department of PathologyMolecular PathologyThe Ohio State University Wexner Medical CenterColumbusOhio
| | - Rulong Shen
- Department of PathologyCollege of MedicineColumbusOhio
| | - Morgan S. Schrock
- Department of Molecular Virology, Immunology and Medical GeneticsThe Ohio State University Comprehensive Cancer CenterColumbusOhio
- Biomedical Sciences Graduate ProgramColumbusOhio
| | - James Liu
- Department of Molecular Virology, Immunology and Medical GeneticsThe Ohio State University Comprehensive Cancer CenterColumbusOhio
- Present address: Beaumont‐Oakland University Medical SchoolGrosse PointeMichigan
| | - Xueliang Pan
- Department of Biomedical InformaticsCenter for BiostatisticsThe Ohio State UniversityColumbusOhio
| | - Donald Quimby
- Department of Molecular Virology, Immunology and Medical GeneticsThe Ohio State University Comprehensive Cancer CenterColumbusOhio
- Present address: University of CincinnatiDepartment of Internal MedicineCincinnatiOhio
| | - Nicola Zanesi
- Department of Molecular Virology, Immunology and Medical GeneticsThe Ohio State University Comprehensive Cancer CenterColumbusOhio
| | - Teresa Druck
- Department of Molecular Virology, Immunology and Medical GeneticsThe Ohio State University Comprehensive Cancer CenterColumbusOhio
| | - Louise Y. Fong
- Department of Pathology, Anatomy & Cell BiologySidney Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaPennsylvania
| | - Kay Huebner
- Department of Molecular Virology, Immunology and Medical GeneticsThe Ohio State University Comprehensive Cancer CenterColumbusOhio
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Hashemian M, Poustchi H, Pourshams A, Khoshnia M, Brockman JD, Hekmatdoost A, Abnet CC, Malekzadeh R. The Nail as a Biomonitor of Trace Element Status in Golestan Cohort Study. Middle East J Dig Dis 2016; 8:19-23. [PMID: 26933477 PMCID: PMC4773078 DOI: 10.15171/mejdd.2016.02] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND
In the Golestan Cohort Study that was launched to investigate the causes of esophageal cancer, a complete biospecimen bank was established for storage of collected blood, urine, hair, and nail samples. The objective of this study was to evaluate the feasibility of nail samples as a biomarker of selected trace elements status.
METHODS
Thirty toenail samples were selected randomly from the participants of Golestan Cohort Study (GCS). The samples were cleaned and analyzed for selenium, mercury, chromium, iron, zinc, and scandium by instrumental neutron activation analysis at the University of Missouri Research Reactor Center. Pearson correlation coefficients were computed for selected trace elements concentration versus scandium concentration to assess terrestrial contamination.
RESULTS
The selenium, zinc, and mercury were not correlated with scandium, suggesting they were free from substantial contamination. The high correlations of scandium with iron and chromium suggest that the iron and chromium levels may be compromised by terrestrial contamination. The coefficients of variation for duplicate samples for selenium and zinc were 2.6% and 7.2%, respectively.
CONCLUSION
The nail samples from Golestan Cohort Study appears to be useable as a biomarker of selenium, zinc, and mercury and could be considered for use in future studies.
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Affiliation(s)
- Maryam Hashemian
- Department of Nutrition, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran ; Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Akram Pourshams
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Khoshnia
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran ; Azar Hospital, Golestan University of Medical Sciences, Gorgan, Iran
| | | | - Azita Hekmatdoost
- Departments of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Christian C Abnet
- Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute,Bethesda, MD, USA
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Bisht G, Rayamajhi S. ZnO Nanoparticles: A Promising Anticancer Agent. Nanobiomedicine (Rij) 2016; 3:9. [PMID: 29942384 PMCID: PMC5998263 DOI: 10.5772/63437] [Citation(s) in RCA: 210] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 04/04/2016] [Indexed: 01/16/2023] Open
Abstract
Nanoparticles, with their selective targeting capabilities and superior efficacy, are becoming increasingly important in modern cancer therapy and starting to overshadow traditional cancer therapies such as chemotherapy radiation and surgery. ZnO nanoparticles, with their unique properties such as biocompatibility, high selectivity, enhanced cytotoxicity and easy synthesis, may be a promising anticancer agent. Zinc, as one of the major trace elements of the human body and co-factor of more than 300 mammalian enzymes, plays an important role in maintaining crucial cellular processes including oxidative stress, DNA replication, DNA repair, cell cycle progression and apoptosis. Thus, it is evident that an alteration in zinc levels in cancer cells can cause a deleterious effect. Research has shown that low zinc concentration in cells leads to the initiation and progression of cancer and high zinc concentration shows toxic effects. Zinc-mediated protein activity disequilibrium and oxidative stress through reactive oxygen species (ROS) may be the probable mechanism of this cytotoxic effect. The selective localization of ZnO nanoparticles towards cancer cells due to enhanced permeability and retention (EPR) effect and electrostatic interaction and selective cytotoxicity due to increased ROS present in cancer cells show that ZnO nanoparticles can selectively target and kill cancer cells, making them a promising anticancer agent.
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Affiliation(s)
- Gunjan Bisht
- Department of Chemical Science and Engineering, Kathmandu University Dhulikhel, Nepal
| | - Sagar Rayamajhi
- Department of Biotechnology, Kathmandu University Dhulikhel, Nepal
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Noncoding RNA Expression Aberration Is Associated with Cancer Progression and Is a Potential Biomarker in Esophageal Squamous Cell Carcinoma. Int J Mol Sci 2015; 16:27824-34. [PMID: 26610479 PMCID: PMC4661918 DOI: 10.3390/ijms161126060] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 11/06/2015] [Accepted: 11/16/2015] [Indexed: 01/01/2023] Open
Abstract
Esophageal cancer is one of the most common cancers worldwide. Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer in Eastern Asian countries. Several types of noncoding RNAs (ncRNAs) function as key epigenetic regulators of gene expression and are implicated in various physiological processes. Unambiguous evidence indicates that dysregulation of ncRNAs is deeply implicated in carcinogenesis, cancer progression and metastases of various cancers, including ESCC. The current review summarizes recent findings on the ncRNA-mediated mechanisms underlying the characteristic behaviors of ESCC that will help support the development of biomarkers and the design of novel therapeutic strategies.
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Taccioli C, Garofalo M, Chen H, Jiang Y, Tagliazucchi GM, Di Leva G, Alder H, Fadda P, Middleton J, Smalley KJ, Selmi T, Naidu S, Farber JL, Croce CM, Fong LY. Repression of Esophageal Neoplasia and Inflammatory Signaling by Anti-miR-31 Delivery In Vivo. J Natl Cancer Inst 2015; 107:djv220. [PMID: 26286729 PMCID: PMC4675101 DOI: 10.1093/jnci/djv220] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Revised: 01/31/2015] [Accepted: 07/20/2015] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Overexpression of microRNA-31 (miR-31) is implicated in the pathogenesis of esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary zinc deficiency. Using a rat model that recapitulates features of human ESCC, the mechanism whereby Zn regulates miR-31 expression to promote ESCC is examined. METHODS To inhibit in vivo esophageal miR-31 overexpression in Zn-deficient rats (n = 12-20 per group), locked nucleic acid-modified anti-miR-31 oligonucleotides were administered over five weeks. miR-31 expression was determined by northern blotting, quantitative polymerase chain reaction, and in situ hybridization. Physiological miR-31 targets were identified by microarray analysis and verified by luciferase reporter assay. Cellular proliferation, apoptosis, and expression of inflammation genes were determined by immunoblotting, caspase assays, and immunohistochemistry. The miR-31 promoter in Zn-deficient esophagus was identified by ChIP-seq using an antibody for histone mark H3K4me3. Data were analyzed with t test and analysis of variance. All statistical tests were two-sided. RESULTS In vivo, anti-miR-31 reduced miR-31 overexpression (P = .002) and suppressed the esophageal preneoplasia in Zn-deficient rats. At the same time, the miR-31 target Stk40 was derepressed, thereby inhibiting the STK40-NF-κΒ-controlled inflammatory pathway, with resultant decreased cellular proliferation and activated apoptosis (caspase 3/7 activities, fold change = 10.7, P = .005). This same connection between miR-31 overexpression and STK40/NF-κΒ expression was also documented in human ESCC cell lines. In Zn-deficient esophagus, the miR-31 promoter region and NF-κΒ binding site were activated. Zn replenishment restored the regulation of this genomic region and a normal esophageal phenotype. CONCLUSIONS The data define the in vivo signaling pathway underlying interaction of Zn deficiency and miR-31 overexpression in esophageal neoplasia and provide a mechanistic rationale for miR-31 as a therapeutic target for ESCC.
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Affiliation(s)
- Cristian Taccioli
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Michela Garofalo
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Hongping Chen
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Yubao Jiang
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Guidantonio Malagoli Tagliazucchi
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Gianpiero Di Leva
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Hansjuerg Alder
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Paolo Fadda
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Justin Middleton
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Karl J Smalley
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Tommaso Selmi
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Srivatsava Naidu
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - John L Farber
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Carlo M Croce
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN)
| | - Louise Y Fong
- Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (CT, MG, GDL, HA, PF, JM, CMC); Kimmel Cancer Center (HC, YJ, KJS, LYF) and Department of Pathology, Anatomy, and Cell Biology (YJ, JLF, LYF), Thomas Jefferson University, Philadelphia, PA; Center for Genome Research (CT, GMT), Department of Life Sciences (TS), University of Modena and Reggio Emilia, Modena, Italy (CT, GMT); Transcriptional Networks in Lung Cancer Group, Manchester Institute, University of Manchester, UK (MG, SN).
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Schaafsma T, Wakefield J, Hanisch R, Bray F, Schüz J, Joy EJM, Watts MJ, McCormack V. Africa's Oesophageal Cancer Corridor: Geographic Variations in Incidence Correlate with Certain Micronutrient Deficiencies. PLoS One 2015; 10:e0140107. [PMID: 26448405 PMCID: PMC4598094 DOI: 10.1371/journal.pone.0140107] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Accepted: 09/21/2015] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND The aetiology of Africa's easterly-lying corridor of squamous cell oesophageal cancer is poorly understood. Micronutrient deficiencies have been implicated in this cancer in other areas of the world, but their role in Africa is unclear. Without prospective cohorts, timely insights can instead be gained through ecological studies. METHODS Across Africa we assessed associations between a country's oesophageal cancer incidence rate and food balance sheet-derived estimates of mean national dietary supplies of 7 nutrients: calcium (Ca), copper (Cu), iron (Fe), iodine (I), magnesium (Mg), selenium (Se) and zinc (Zn). We included 32 countries which had estimates of dietary nutrient supplies and of better-quality GLOBCAN 2012 cancer incidence rates. Bayesian hierarchical Poisson lognormal models were used to estimate incidence rate ratios for oesophageal cancer associated with each nutrient, adjusted for age, gender, energy intake, phytate, smoking and alcohol consumption, as well as their 95% posterior credible intervals (CI). Adult dietary deficiencies were quantified using an estimated average requirements (EAR) cut-point approach. RESULTS Adjusted incidence rate ratios for oesophageal cancer associated with a doubling of mean nutrient supply were: for Fe 0.49 (95% CI: 0.29-0.82); Mg 0.58 (0.31-1.08); Se 0.40 (0.18-0.90); and Zn 0.29 (0.11-0.74). There were no associations with Ca, Cu and I. Mean national nutrient supplies exceeded adult EARs for Mg and Fe in most countries. For Se, mean supplies were less than EARs (both sexes) in 7 of the 10 highest oesophageal cancer ranking countries, compared to 23% of remaining countries. For Zn, mean supplies were less than the male EARs in 8 of these 10 highest ranking countries compared to in 36% of other countries. CONCLUSIONS Ecological associations are consistent with the potential role of Se and/or Zn deficiencies in squamous cell oesophageal cancer in Africa. Individual-level analytical studies are needed to elucidate their causal role in this setting.
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Affiliation(s)
- Torin Schaafsma
- Department of Epidemiology, University of Washington, Seattle, WA, United States of America
| | - Jon Wakefield
- Department of Biostatistics, University of Washington, Seattle, WA, United States of America
| | - Rachel Hanisch
- Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France
| | - Freddie Bray
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Joachim Schüz
- Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France
| | - Edward J. M. Joy
- Centre for Environmental Geochemistry, Inorganic Geochemistry, British Geological Survey, Nottingham, United Kingdom
- School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom
| | - Michael J. Watts
- Centre for Environmental Geochemistry, Inorganic Geochemistry, British Geological Survey, Nottingham, United Kingdom
| | - Valerie McCormack
- Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France
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