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Smet A, Kupcinskas J, Link A, Hold GL, Bornschein J. The Role of Microbiota in Gastrointestinal Cancer and Cancer Treatment: Chance or Curse? Cell Mol Gastroenterol Hepatol 2021; 13:857-874. [PMID: 34506954 PMCID: PMC8803618 DOI: 10.1016/j.jcmgh.2021.08.013] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 08/18/2021] [Accepted: 08/18/2021] [Indexed: 02/08/2023]
Abstract
The gastrointestinal (GI) tract is home to a complex and dynamic community of microorganisms, comprising bacteria, archaea, viruses, yeast, and fungi. It is widely accepted that human health is shaped by these microbes and their collective microbial genome. This so-called second genome plays an important role in normal functioning of the host, contributing to processes involved in metabolism and immune modulation. Furthermore, the gut microbiota also is capable of generating energy and nutrients (eg, short-chain fatty acids and vitamins) that are otherwise inaccessible to the host and are essential for mucosal barrier homeostasis. In recent years, numerous studies have pointed toward microbial dysbiosis as a key driver in many GI conditions, including cancers. However, comprehensive mechanistic insights on how collectively gut microbes influence carcinogenesis remain limited. In addition to their role in carcinogenesis, the gut microbiota now has been shown to play a key role in influencing clinical outcomes to cancer immunotherapy, making them valuable targets in the treatment of cancer. It also is becoming apparent that, besides the gut microbiota's impact on therapeutic outcomes, cancer treatment may in turn influence GI microbiota composition. This review provides a comprehensive overview of microbial dysbiosis in GI cancers, specifically esophageal, gastric, and colorectal cancers, potential mechanisms of microbiota in carcinogenesis, and their implications in diagnostics and cancer treatment.
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Affiliation(s)
- Annemieke Smet
- Laboratory of Experimental Medicine and Paediatrics, Faculty of Medicine and Health Sciences; Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium
| | - Juozas Kupcinskas
- Institute for Digestive Research, Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Georgina L Hold
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia
| | - Jan Bornschein
- Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
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Jonaitis P, Kupcinskas L, Kupcinskas J. Molecular Alterations in Gastric Intestinal Metaplasia. Int J Mol Sci 2021; 22:ijms22115758. [PMID: 34071181 PMCID: PMC8199079 DOI: 10.3390/ijms22115758] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/24/2021] [Accepted: 05/26/2021] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer (GC) remains one of the most common causes of mortality worldwide. Intestinal metaplasia (IM) is one of the preneoplastic gastric lesions and is considered an essential predisposing factor in GC development. Here we present a review of recent most relevant papers to summarize major findings on the molecular alterations in gastric IM. The latest progress in novel diagnostic methods allows scientists to identify various types of molecular alterations in IM, such as polymorphisms in various genes, changes in the expression of micro-RNAs and long noncoding RNAs, and altered microbiome profiles. The results have shown that some of these alterations have strong associations with IM and a potential to be used for screening, treatment, and prognostic purposes; however, one of the most important limiting factors is the inhomogeneity of the studies. Therefore, further large-scale studies and clinical trials with standardized methods designed by multicenter consortiums are needed. As of today, various molecular alterations in IM could become a part of personalized medicine in the near future, which would help us deliver a personalized approach for each patient and identify those at risk of progression to GC.
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Jonaitis P, Kiudelis V, Streleckiene G, Gedgaudas R, Skieceviciene J, Kupcinskas J. Novel Biomarkers in the Diagnosis of Benign and Malignant Gastrointestinal Diseases. Dig Dis 2021; 40:1-13. [PMID: 33647906 DOI: 10.1159/000515522] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 02/26/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Various noninvasive biomarkers have been used in the diagnosis, prognosis, and treatment of different gastrointestinal (GI) diseases for years. Novel technological developments and profound perception of molecular processes related to GI diseases over the last decade have allowed researchers to evaluate genetic, epigenetic, and many other potential molecular biomarkers in different diseases and clinical settings. Here, we present a review of recent and most relevant articles in order to summarize major findings on novel biomarkers in the diagnosis of benign and malignant GI diseases. SUMMARY Genetic variations, noncoding RNAs (ncRNAs), cell-free DNA (cfDNA), and microbiome-based biomarkers have been extensively analyzed as potential biomarkers in benign and malignant GI diseases. Multiple single-nucleotide polymorphisms have been linked with a number of GI diseases, and these observations are further being used to build up disease-specific genetic risk scores. Micro-RNAs and long ncRNAs have a large potential as noninvasive biomarkers in the management of inflammatory bowel diseases and GI tumors. Altered microbiome profiles were observed in multiple GI diseases, but most of the findings still lack translational clinical application. As of today, cfDNA appears to be the most potent biomarker for early detection and screening of GI cancers. Key Messages: Novel noninvasive molecular biomarkers show huge potential as useful tools in the diagnostics and management of different GI diseases. However, the use of these biomarkers in real-life clinical practice still remains limited, and further large studies are needed to elucidate the ultimate role of these potential noninvasive clinical tools.
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Affiliation(s)
- Paulius Jonaitis
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Vytautas Kiudelis
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Greta Streleckiene
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Rolandas Gedgaudas
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Jurgita Skieceviciene
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Juozas Kupcinskas
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
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Urba M, Skieceviciene J, Janciauskas D, Jonaitis L, Kupcinskas L, Fassan M, Rugge M, Kupcinskas J. Gastritis Stages in Monozygotic and Dizygotic Dyspeptic Twins. Gastroenterol Res Pract 2020; 2020:9510717. [PMID: 32714389 PMCID: PMC7352144 DOI: 10.1155/2020/9510717] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 05/30/2020] [Accepted: 06/01/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The progression of Helicobacter pylori-associated gastritis towards atrophic gastritis is modulated by host-related and environmental factors. Studies that explore the possible involvement of host-related versus environmental factors in the development of gastritis phenotype induced by H. pylori are highly needed. AIMS Our study was aimed at investigating the phenotype of H. pylori-associated gastritis in two cohorts of monozygotic and dizygotic twins, using the OLGA/OLGIM gastritis staging system. METHODS Two cohorts of monozygotic (14 pairs) and dizygotic (15 pairs) dyspeptic twins prospectively underwent endoscopy with biopsy sampling based on Sydney protocol. H. pylori status and OLGA/OLGIM stages were assessed and compared. RESULTS The mean age of monozygotic and dizygotic twins was 40.4 and 38.6 years, respectively (p = 0.623). The overall prevalence of H. pylori infection was 51.7%. Among the 14 monozygotic twin pairs, five pairs were H. pylori-positive, four were H. pylori-negative, and five were H. pylori-discordant. Among the 15 dizygotic twin pairs, five pairs were H. pylori-positive, five were H. pylori-negative, and five were H. pylori-discordant. Concordance for antrum atrophy in monozygotic twins was 78.6% (11/14 pairs) and in dizygotic twins 73.3% (11/15 pairs) (p = 0.742). Concordance for corpus atrophy in monozygotic versus dizygotic twins was 92.9% (13/14 pairs) and 86.7% (13/15 pairs), respectively (p = 0.584). Concordance for antrum intestinal metaplasia (IM) in monozygotic twins was 85.7% (12/14 pairs) and in dizygotic 73.3% (11/15 pairs) (p = 0.411). Concordance for corpus IM in monozygotic twins was 85.7% (12/14 pairs) and in dizygotic 86.7% (13/15 pairs) (p = 0.941). Among monozygotic and dizygotic subjects, the stage of gastritis was concordant in both H. pylori-positive and H. pylori-negative subjects. CONCLUSIONS In conclusion, histological gastric mucosa alterations in monozygotic and dizygotic twins showed high rates of concordance. Furthermore, OLGA/OLGIM gastritis stages were not modulated by the zygosity of the twins.
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Affiliation(s)
- Mindaugas Urba
- Department of Gastroenterology, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Jurgita Skieceviciene
- Department of Gastroenterology, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Dainius Janciauskas
- Department of Pathological Anatomy, Lithuanian University of Health Sciences, Kaunas LT 50161, Lithuania
| | - Laimas Jonaitis
- Department of Gastroenterology, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Limas Kupcinskas
- Department of Gastroenterology, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua 35121, Italy
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua 35121, Italy
- Veneto Cancer Registry, Regional Authority, Padova 35100, Italy
| | - Juozas Kupcinskas
- Department of Gastroenterology, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
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Rech TF, Mazzoleni LE, Mazzoleni F, Francesconi CFDM, Sander GB, Michita RT, Nabinger DD, de Bona LR, Milbradt TC, Ott EA, Breyer HP, Haas GM, Canevese AP, Stifft J, Simon D. Analysis of the Influence of Interleukin-1β Gene Polymorphism on Gastric Inflammatory Response and Precancerous Lesions Development in Patients with Functional Dyspepsia. Immunol Invest 2020; 49:585-596. [PMID: 31909646 DOI: 10.1080/08820139.2019.1710532] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Tássia Flores Rech
- Human Molecular Genetics Laboratory, Universidade Luterana do Brasil, Canoas, Brazil
| | - Luiz Edmundo Mazzoleni
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Felipe Mazzoleni
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | | | | | - Rafael Tomoya Michita
- Human Molecular Genetics Laboratory, Universidade Luterana do Brasil, Canoas, Brazil
| | | | - Laura Renata de Bona
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | | | - Eduardo André Ott
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | | | - Gelline Maria Haas
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Ane Paula Canevese
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Jonathas Stifft
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Daniel Simon
- Human Molecular Genetics Laboratory, Universidade Luterana do Brasil, Canoas, Brazil
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Hirbod-Mobarakeh A, Shabani M, Keshavarz-Fathi M, Delavari F, Amirzargar AA, Nikbin B, Kutikhin A, Rezaei N. Immunogenetics of Cancer. CANCER IMMUNOLOGY 2020:417-478. [DOI: 10.1007/978-3-030-30845-2_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Jonaitis P, Jonaitis L, Kupcinskas J. Role of Genetic Polymorphisms of Cytochrome P450 2C19 in Pantoprazole Metabolism and Pantoprazole-based Helicobacter pylori Eradication Regimens. Curr Drug Metab 2020; 21:830-837. [PMID: 32407266 DOI: 10.2174/1389200221666200514081442] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 01/11/2020] [Accepted: 02/09/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Cytochrome P450 (CYP450) enzymes play an important role in the metabolism of 70-80% of the currently used medications, including proton pump inhibitors. There are some data analyzing the impact of gene polymorphisms of CYP450 enzymes on most widely used PPIs, such as omeprazole, however, the data on pantoprazole are highly lacking. OBJECTIVE To summarize the most recent publications and studies on the role of polymorphisms of the genes encoding CYP450 enzyme 2C19 in the metabolism of pantoprazole and pantoprazole based Helicobacter pylori eradication regimens. METHODS We performed a non-systematic search of the available literature on the selected topic. RESULTS AND CONCLUSION The data on cytochrome P450 gene polymorphisms and their role in pantoprazole metabolism and pantoprazole based Helicobacter pylori eradication remain conflicting. Individual differences in pantoprazole metabolism might be partly related to genetic polymorphisms of CYP450 enzymes. Most of the studies support the observation that cytochrome 2C19 polymorphisms have an impact on the pharmacokinetics of pantoprazole and its therapeutic effects: poor metabolizers of PPIs are more likely to have a better response to pantoprazole therapy and achieve better H. pylori eradication rates compared to rapid metabolizers. The determination of alleles that are associated with decreased (e.g., *2, *3 alleles) or increased (e.g., *17 allele) cytochrome 2C19 enzyme activity might be used as predictive factors for the potential of acid suppression and the success of Helicobacter pylori eradication. Overall, currently available data do not provide robust evidence, therefore, the application of genetic polymorphisms of cytochrome enzymes in clinical practice still cannot be recommended as routine practice for personalized pantoprazole prescription strategies.
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Affiliation(s)
- Paulius Jonaitis
- Faculty of Medicine, Medical Academy, Eiveniu str. 2 LT-50161, Kaunas, Lithuania
| | - Laimas Jonaitis
- Department of Gastroenterology, Lithuanian Eiveniu str. 2 LT-50161, Kaunas, Lithuania
| | - Juozas Kupcinskas
- Department of Gastroenterology, Lithuanian Eiveniu str. 2 LT-50161, Kaunas, Lithuania
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Sultana Z, Bankura B, Pattanayak AK, Sengupta D, Sengupta M, Saha ML, Panda CK, Das M. Association of Interleukin-1 beta and tumor necrosis factor-alpha genetic polymorphisms with gastric cancer in India. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2018; 59:653-667. [PMID: 30094865 DOI: 10.1002/em.22208] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 03/18/2018] [Accepted: 05/03/2018] [Indexed: 06/08/2023]
Abstract
Interleukin 1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α) are key inflammatory cytokines whose polymorphisms have been correlated with increased susceptibility to gastric cancer (GC). Since geographical and racial differences exist in cancer rates, our study was aimed to evaluate the first possible association of polymorphisms in these genes with GC risk in West Bengal, India. Polymorphisms in IL-1β and TNF-α genes were genotyped in 120 GC patients and 135 healthy individuals. Combined effect of the SNPs in both genes with GC risk was determined through allele dosage analysis (ADA) and the survival data were analyzed by Log Rank Test. The study results revealed that IL-1β rs1143627: T > C, rs16944: C > T (p = 0.001;OR = 1.85; 95% CI 1.30-2.63) and rs1143633: G > A (p < 0.0001; OR = 2.53; 95% CI 1.67-3.83) and TNF-α rs1800630: C > A, rs1799964: T > C (p < 0.0001; OR = 2.31; 95% CI 1.54-3.46) polymorphisms significantly contributed toward GC risk. Moreover, ADA showed that carriage of 7 "effective" risk alleles conferred a risk of almost 10-fold in comparison to individuals carrying less than 3 "effective" risk alleles. Our survival analysis also indicated a significant association between IL-1β rs1143627: T > C and rs16944: C > T and patient survivability. The presence of H. pylori enhanced the risk in individuals with IL-1β rs1143627:CC and rs16944:TT genotypes. Further, meta-analysis revealed significant association of IL-1β rs1143627: T > C (p = 0.026; OR = 4.165; 95% CI 1.18-14.65) and rs16944: C > T (p = 0.01; OR = 5.49; 95% CI 1.48-20.37) in presence of H. pylori with gastric cancer in Asian population though no significant difference (p > 0.05) was found when compared to absence of H. pylori Environ. Mol. Mutagen. 59:653-667, 2018. © 2018 Wiley Periodicals, Inc.
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Affiliation(s)
- Zareen Sultana
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, 700019, India
| | - Biswabandhu Bankura
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, 700019, India
| | | | - Debmalya Sengupta
- Department of Genetics, University of Calcutta, West Bengal, 700019, India, Kolkata
| | - Mainak Sengupta
- Department of Genetics, University of Calcutta, West Bengal, 700019, India, Kolkata
| | - Makhan Lal Saha
- Department of Surgery, Institute of Post Graduate Medical Education &Research, Kolkata, West Bengal, 700020, India
| | - Chinmay Kumar Panda
- Department of Oncogene Regulation and Viral Associated Human Cancer, Chittaranjan Cancer Research Institute, Kolkata, West Bengal, 700026, India
| | - Madhusudan Das
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, 700019, India
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Eaton KD, Romine PE, Goodman GE, Thornquist MD, Barnett MJ, Petersdorf EW. Inflammatory Gene Polymorphisms in Lung Cancer Susceptibility. J Thorac Oncol 2018; 13:649-659. [PMID: 29408308 DOI: 10.1016/j.jtho.2018.01.022] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Revised: 01/09/2018] [Accepted: 01/26/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. METHODS A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the β-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [IFNG], interleukin 10 gene [IL10], interleukin 1 alpha gene [IL1A], interleukin 1 beta gene [IL1B], interleukin 2 gene [IL2], interleukin 4 receptor gene [IL4R], interleukin 4 gene [IL4], interleukin 6 gene [IL6], prostaglandin-endoperoxide synthase 2 gene [PTGS2] (also known as COX2), transforming growth factor beta 1 gene [TGFB1], and tumor necrosis factor alpha gene [TNFA]) was evaluated. RESULTS Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1β-511C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58-0.94] and OR = 0.71 [95% CI: 0.50-1.01], respectively, p = 0.03). Similar results were observed for the IL-1β-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59-0.95] and OR = 0.69 [95% CI: 0.46-1.03], respectively, p = 0.03). Survival was not influenced by genotype. CONCLUSIONS This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer.
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Affiliation(s)
- Keith D Eaton
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
| | - Perrin E Romine
- Department of Medicine, University of Washington, Seattle, Washington
| | - Gary E Goodman
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Mark D Thornquist
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Biostatistics, University of Washington, Seattle, Washington
| | - Matt J Barnett
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Effie W Petersdorf
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington
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Javan B, Kalani MR, Shahbazi M. Interleukin-1 gene cluster Haplotype analysis in the chronic outcome prediction of the Hepatitis B virus infection. J Med Virol 2017; 90:510-517. [PMID: 29023858 DOI: 10.1002/jmv.24972] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Accepted: 10/08/2017] [Indexed: 12/23/2022]
Abstract
Hepatitis B virus (HBV) infection is well known as an important cause of the chronic liver disease. The screening of the genotype of certain cytokines might be helpful to predict the clinical outcome of an HBV infection. The present study investigates the relationship between the polymorphism and haplotypes of the Interleukin-1 (IL-1) gene family, including IL-1-alpha (IL-1A), IL-1-beta (IL-1B,) and IL-1 receptor antagonist (IL-1RN), with chronic HBV infection. A total of 297 chronic HBV and 333 matched on sex and age control individuals were genotyped using the standard sequence-specific-polymerase chain reaction primer (SSP-PCR) method. Four different haplotype analysis software packages were applied for data interpretation. The results showed excess genotype A1/A1 and A2/A2 at IL-1RN (40.2%, 39.9%), C/T at IL-1A-889 (55.6%), and C/C at IL-1B-511 (41.1%) in controls while A1/A1 at IL-1RN (59.3%), T/T at IL-1B-31 (46.5%), C/T at IL-1B + 3953 (65%), in chronic HBV infection cases. A total of 148 haplotypes were observed overall (96 in the case group and 89 in the control group). The haplotype combination of genotype A1/A1 at IL1-RN along with a C/T for all three IL-1B polymorphic positions and either C/T or T/T at the IL-1A-899 position may increase the probability of the chronic outcome for the HBV infection.
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Affiliation(s)
- Bita Javan
- Medical Cellular & Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mohamad R Kalani
- Medical Cellular & Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.,University of Illinois at Urbana-Champaign, Molecular and Cell Biology, Urbana, Illinois
| | - Majid Shahbazi
- Medical Cellular & Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran
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Petkevicius V, Salteniene V, Juzenas S, Wex T, Link A, Leja M, Steponaitiene R, Skieceviciene J, Kupcinskas L, Jonaitis L, Kiudelis G, Malfertheiner P, Kupcinskas J. Polymorphisms of microRNA target genes IL12B, INSR, CCND1 and IL10 in gastric cancer. World J Gastroenterol 2017; 23:3480-3487. [PMID: 28596683 PMCID: PMC5442083 DOI: 10.3748/wjg.v23.i19.3480] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 02/23/2017] [Accepted: 03/21/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate associations between miRNA target genes IL12B, INSR, CCND1 and IL10 polymorphisms and gastric cancer (GC) in European population. METHODS Gene polymorphisms were analyzed in 508 controls and 474 GC patients from 3 tertiary centers in Germany, Lithuania and Latvia. Controls were patients from the out-patient departments, who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy. Gastric cancer (GC) patients had histopathological verification of gastric adenocarcinoma. Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells. IL12B T>G (rs1368439), INSR T>C (rs1051690), CCND1 A>C (rs7177) and IL10 T>C (rs3024498) SNPs were genotyped by the real-time polymerase chain reaction. Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex, age and country of birth. RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690. The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls (23.26% and 19.19% respectively, P = 0.028). CT genotype was also more prevalent in patients compared to control group (38.48% and 30.12% respectively, P < 0.021). Logistic regression analysis revealed that only one polymorphism (rs1051690 in INSR gene) was associated with increased risk of GC. Carriers of CT genotype had higher odds of GC when compared to CC genotype (OR = 1.45, 95%PI: 1.08-1.95, P = 0.01). Similar association was observed in a dominant model for INSR gene, where comparison of TT+CT vs CC genotypes showed an increased risk of GC (OR = 1.44, 95%PI: 1.08-1.90, P = 0.01). Other analyzed SNPs were not associated with the presence of GC. CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC, while polymorphisms in IL12B, CCND1 and IL10 genes are not linked with the presence of GC.
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Sun X, Cai H, Li Z, Li S, Yin W, Dong G, Kuai J, He Y, Jia J. Association between IL-1β polymorphisms and gastritis risk: A meta-analysis. Medicine (Baltimore) 2017; 96:e6001. [PMID: 28151895 PMCID: PMC5293458 DOI: 10.1097/md.0000000000006001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 01/05/2017] [Accepted: 01/06/2017] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection of the human stomach regularly leads to chronic gastric inflammation. The cytokine gene interleukin (IL)-1β has been implicated in influencing the pathology of inflammation induced by H. pylori infection. Currently, several studies have been carried out to investigate the association of IL-1β-511 (rs16944) and IL-1β-31 (rs1143627) polymorphisms with gastritis risk; however, the results are inconsistent and inconclusive. To assess the effect of IL-1β polymorphisms on gastritis susceptibility, we conducted a meta-analysis. METHODS Up to March 15, 2016, 2205 cases and 2289 controls were collected from 12 published case-control studies. Summarized odds ratios and corresponding 95% confidence intervals (CIs) for IL-1β-511 and IL-1β-31 polymorphisms and gastritis risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses and logistic meta-regression analyses. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed. RESULTS The results provided evidences that the single nucleotide polymorphisms (SNPs) in IL-1β-31 might be associated with the gastritis risk, especially in the Caucasian population, while SNPs in the IL-1β-511 might not be. CONCLUSION Our studies may be helpful in supplementing the disease monitoring of gastritis in the future, and additional studies to determine the exact molecular mechanisms might inspire interventions to protect the susceptible subgroups.
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Affiliation(s)
- Xiaoming Sun
- Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu
| | - Hongxing Cai
- Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu
| | - Zhouru Li
- Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu
| | - Shanshan Li
- Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu
| | - Wenjiang Yin
- Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu
| | - Guokai Dong
- Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu
| | - Jinxia Kuai
- Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu
| | | | - Jing Jia
- Center for Molecular Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, P. R. China
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Hong JB, Zuo W, Wang AJ, Lu NH. Helicobacter pylori Infection Synergistic with IL-1β Gene Polymorphisms Potentially Contributes to the Carcinogenesis of Gastric Cancer. Int J Med Sci 2016; 13:298-303. [PMID: 27076787 PMCID: PMC4829543 DOI: 10.7150/ijms.14239] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 03/31/2016] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection is the most common chronic bacterial infection in the world and the etiological agent for most gastric cancer (GC). Interleukin-1β (IL-1β) is a potent proinflammatory cytokine, and its deregulation is closely associated with the tumorigenesis of several cancers. Recent studies have revealed that the IL-1β-31 and -511T alleles are closely associated with gastric carcinogenesis due to their roles in the induction of gastric precancerous lesions and hypochlorhydria. Furthermore, H. pylori infection has a synergistic effect on the development of GC with IL-1β gene polymorphisms, and the highest prevalence of severe gastric abnormalities are found in patients with both host and bacterial high-risk genotypes (cagA(+)/vacAs1(+)/IL-1β-511T). Therefore, these recent advances demonstrate that H. pylori synergistic with IL-1β gene polymorphisms contribute to the gastric carcinogenesis by their involvement in precancerous gastric lesions and low gastric acid secretion.
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Affiliation(s)
- Jun-Bo Hong
- 1. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Wei Zuo
- 2. Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
| | - An-Jiang Wang
- 1. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Nong-Hua Lu
- 1. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
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Hirbod-Mobarakeh A, Amirzargar AA, Nikbin B, Nicknam MH, Kutikhin A, Rezaei N. Immunogenetics of Cancer. CANCER IMMUNOLOGY 2015:295-341. [DOI: 10.1007/978-3-662-44006-3_17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Kim J, Kim Y, Lee KA. Ethnic differences in gastric cancer genetic susceptibility: allele flips of interleukin gene. World J Gastroenterol 2014; 20:4558-4565. [PMID: 24782608 PMCID: PMC4000492 DOI: 10.3748/wjg.v20.i16.4558] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 12/12/2013] [Accepted: 03/08/2014] [Indexed: 02/06/2023] Open
Abstract
Polymorphisms in promoter regions of inflammatory cytokines have been widely studied, and potentially functional polymorphisms have been discovered. Conflicting results from meta-analyses of interleukin (IL)-1B and IL-10 polymorphisms show differences in gastric cancer susceptibilities between Caucasian and Asian populations. In particular, we note the suggestion of an allele flip in IL-1B and IL-10 gene polymorphisms. In Asian populations, the IL-1B-1464G/-511C/-31T haplotype indicates risk for gastric cancer, while the opposite haplotype, IL-1B-1464C/-511T/-31C is the risk-related allele in Caucasians. Furthermore, while IL-10-1082G/-819C/-592C is associated with gastric cancer in Asians, IL-10-1082A/-819T/-592T is linked to gastric cancer risk in Caucasians. These seemingly contradictory results may be attributed to distinct carcinogenic mechanisms underlying the different gastric cancer subtypes. The allele flip observed in IL-10 and gastric cancer appears to reflect allelic heterogeneity, similar to that observed in IL-1B. In this review, we focus on the allele flip phenomenon observed between different ethnic groups in an effort to resolve certain controversial results from recent studies on interleukin polymorphism. In addition, we re-emphasize the importance of stratifying gastric cancer subtypes based on anatomical site and Lauren classification to prevent false associations arising through dilution of true ones.
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Abstract
Helicobacter pylori infection has been recognized as the main trigger of stomach-related diseases. The huge variation in H. pylori infection patterns across the globe requires targeted research and close monitoring of this infection in different regions. The Baltic countries have witnessed enormous changes in socioeconomic conditions in the last years. Evolution of H. pylori infection and related diseases has been a key interest of gastroenterology centers in the Baltic States over the last two decades, translating into up-to-date scientific data that are valuable locally and on the European level. The East-West gradient in the prevalence of H. pylori infection is still evident in the Baltic countries, but the gap is becoming smaller, and similar trends are expected for the coming years. Clarithromycin-based triple therapy remains the first-line treatment of H. pylori in the region; however, careful monitoring of resistance rates in the future remains highly relevant, though routine resistance testing is not available in all the countries. A high prevalence of gastric cancer is still notable in the Baltic States; nevertheless, a steady decline in gastric cancer incidence in Lithuania, Latvia and Estonia is present and expected to be continuing during the coming decades. Currently, H. pylori-related diseases still constitute a substantial part of gastroenterologists' workload in the region. This paper reviews epidemiological, diagnostic, treatment as well as basic research trends on H. pylori infection and related diseases in the Baltic States during the last two decades.
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Affiliation(s)
- Juozas Kupcinskas
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
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17
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Abstract
Infection with Helicobacter pylori is established as the major risk factor for gastric cancer development. Damage of the mucosal barrier due to H. pylori-induced inflammation enhances the carcinogenic effect of other risk factors such as salt intake or tobacco smoking. The genetic disposition of both the bacterial strain and the host can increase the potential towards gastric cancer formation. Genetic variance of the bacterial proteins CagA and VacA is associated with a higher gastric cancer risk, as are polymorphisms and epigenetic changes in host gene coding for interleukins (IL1β, IL8), transcription factors (CDX2, RUNX3) and DNA repair enzymes. Application of high-throughput assays for genome-wide assessment of either genetic structural variance or gene expression patterns may lead to a better understanding of the pathobiological background of these processes, including the underlying signaling pathways. Understanding of the stepwise alterations that take place in the transition from chronic atrophic gastritis, via metaplastic changes, to invasive neoplasia is vital to define the 'point of no return' before which eradication of H. pylori has the potential to prevent gastric cancer. Currently, eradication as preventive strategy is only recommended for high-incidence regions in Asia; large population studies with an adequate follow-up are required to demonstrate the effectiveness of such an approach in Western populations.
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Affiliation(s)
- Jan Bornschein
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University of Magdeburg, Magdeburg, Germany
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18
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Kupcinskas J, Wex T, Link A, Leja M, Bruzaite I, Steponaitiene R, Juzenas S, Gyvyte U, Ivanauskas A, Ancans G, Petrenkiene V, Skieceviciene J, Kupcinskas L, Malfertheiner P. Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer. PLoS One 2014; 9:e87467. [PMID: 24475294 PMCID: PMC3903675 DOI: 10.1371/journal.pone.0087467] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2013] [Accepted: 12/26/2013] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND AND AIMS MicroRNAs (miRNAs) are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC) and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608) and the presence of GC or high risk atrophic gastritis (HRAG) in European population. METHODS Gene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281) of European descent. MiR-27a T>C (rs895819), miR-146a G>C (rs2910164), miR-196a-2 C>T (rs11614913), miR-492 G>C (rs2289030) and miR-608 C>G (rs4919510) SNPs were genotyped by RT-PCR. RESULTS Overall, SNPs of miRNAs were not associated with the presence of GC or HRAG. We observed a tendency for miR-196a-2 CT genotype to be associated with higher risk of GC when compared to CC genotype, however, the difference did not reach the adjusted P-value (odds ratio (OR) - 1.46, 95% confidence interval (CI) 1.03-2.07, P = 0.032). MiR-608 GG genotype was more frequent in GC when compared to controls (OR -2.34, 95% CI 1.08-5.04), but significance remained marginal (P = 0.029). A similar tendency was observed in a recessive model for miR-608, where CC + CG vs GG genotype comparison showed a tendency for increased risk of GC with OR of 2.44 (95% CI 1.14-5.22, P = 0.021). The genotypes and alleles of miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 SNPs had similar distribution between histological subtypes of GC and were not linked with the presence of diffuse or intestinal-type GC. CONCLUSIONS Gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of HRAG, GC or different histological subtypes of GC in European subjects.
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Affiliation(s)
- Juozas Kupcinskas
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Thomas Wex
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany
- Medical Laboratory for Clinical Chemistry, Microbiology and Infectious Diseases, Department of Molecular Genetics, Magdeburg, Germany
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia
- Digestive Diseases Center GASTRO, Riga, Latvia
- Riga East University Hospital, Riga, Latvia
| | - Indre Bruzaite
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Ruta Steponaitiene
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Simonas Juzenas
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Ugne Gyvyte
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Audrius Ivanauskas
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Guntis Ancans
- Digestive Diseases Center GASTRO, Riga, Latvia
- Riga East University Hospital, Riga, Latvia
| | - Vitalija Petrenkiene
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Jurgita Skieceviciene
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Limas Kupcinskas
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany
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Ryberg A, Petersson F, Redeen S, Eriksson O, Borch K. Host Gene Polymorphisms in Relation to Helicobacter Pylori Infection and Associated Diseases in a Population Based Cohort. Gastroenterology Res 2013; 6:207-218. [PMID: 27785255 PMCID: PMC5051128 DOI: 10.4021/gr578w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/06/2013] [Indexed: 12/12/2022] Open
Abstract
Background This prospective population based cohort study explores possible associations between host gene polymorphisms, blood group and life style factors on the one hand, and Helicobacter pylori infection, peptic ulcer, and the grade of inflammation, atrophy and intestinal metaplasia of the gastric mucosa, on the other hand. Methods The study population (472 volunteers) has previously undergone screening with gastroduodenoscopy, biopsy and blood sampling. The host gene polymorphisms of IL1B-31C/T, IFNGR1-56T/C, the IL1RN VNTR in exon 2 and the HLA-DRB1 gene alleles were analyzed using PCR and pyrosequencing. Results H. pylori infection was negatively related to HLA DRB1*03 (odds ratio (OR) 95% CI: 0.388 - 0.989) and was more frequent in individuals with blood group O than A (OR 95% CI: 1.121 - 2.677). There was a lower risk of moderate to severe inflammation in the antrum among individuals with IL1B-31 TC compared to CC carriers (OR 95% CI: 0.094 - 0.733). The IL1RN*L2 genotype was associated with higher risk of IM in the antrum than the *LL genotype (OR 95% CI: 1.570 - 15.878). There was a negative relation between the HLA DRB1 alleles *04 (OR 95% CI: 0.234 - 0.831) and *08 (OR 95% CI: 0.013 - 0.915), and IM in the antrum. Conclusion The IL1RN VNTR and the IL1β-31 alleles seem to be associated with intestinal metaplasia of the corpus mucosa and the grade of inflammation of the antrum, respectively. However, no unambiguous correlations could be identified between the host polymorphisms and the occurrence of H. pylori infection, peptic ulcer, and the grade of inflammation, atrophy and IM of the gastric mucosa.
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Affiliation(s)
- Anna Ryberg
- Department of Clinical Microbiology, Centre for Diagnostics, County Council of Ostergotland, Sweden; Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Sweden
| | - Fredrik Petersson
- Department of Pathology, National University Health System Singapore. Previously Department of Pathology, Karolinska University Hospital, Stockholm, Sweden
| | - Stefan Redeen
- Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Sweden
| | - Olle Eriksson
- Department of Computer and Information Science, Faculty of Arts and Sciences, Linkoping University, Sweden
| | - Kurt Borch
- Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Sweden
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Wang Q, Ju J. Progress in understanding the association between interleukin-1B gene polymorphisms and susceptibility to gastric cancer. Shijie Huaren Xiaohua Zazhi 2013; 21:3493-3498. [DOI: 10.11569/wcjd.v21.i32.3493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is one of severe diseases threatening human health and has a close association with Helicobacter pylori infection. Interleukin-1B (IL-1B) gene polymorphisms have been suggested to be associated with susceptibility to gastric cancer; however, there is still controversy over this point of view. In this paper we will summarize recent progress in understanding the association between IL-1B gene polymorphisms and susceptibility to gastric cancer in population in different areas or of different races
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Lee SY, Kang DB, Park WC, Lee JK, Chae SC. Association of CTTN polymorphisms with the risk of colorectal cancer. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2012; 82:156-164. [PMID: 22403749 PMCID: PMC3294109 DOI: 10.4174/jkss.2012.82.3.156] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/23/2011] [Revised: 12/25/2011] [Accepted: 01/02/2012] [Indexed: 11/30/2022]
Abstract
PURPOSE Various studies searching for biomarkers to predict tumor metastasis or prognosis in both esophageal squamous cell carcinoma (ESCC) and head and neck squamous cell carcinoma (HNSCC) are currently underway. However, few data have been reported on its association with colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) are the most common known form of human genetic variation and may contribute to an increased susceptibility to cancer including CRC. The present study aimed to investigate whether the polymorphisms in the CTTN gene are associated with susceptibility to CRC in the Korean population. METHODS A case-control study was performed to examine the relationship between the CTTN g.-9101C>T, g.-8748C>T, and g.72C>T polymorphisms and the risk of CRC. Polymerase chain reaction-restriction fragment length polymorphism analysis of g.-8748C>T, g.-9101C>T and Taqman analysis of g.72C>T were performed on blood samples from 218 patients with CRC and 533 control individuals. The g.-9101C>T, g.-8748C>T, and g.72C>T SNPs in CTTN and their haplotypes were analyzed. RESULTS The genotype and allele frequencies of g.-9101C>T, g.-8748C>T, and g.72C>T did not differ between the patient group and the control group. Further, the haplotype of CTTN g.-9101C>T, g.-8748C>T, and g.72C>T did not differ between patient group and the control group. However, the genotype and allele frequencies of CTTN g.-9101C>T were significantly increased in the lymph node positive CRC group compared to the control group. CONCLUSION The CTTN g.-9101C>T polymorphism may influence lymph node positive CRC.
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Affiliation(s)
- Seok Youn Lee
- Department of Surgery, Digestive Disease Research Institute and Institute of Medical Science, Wonkwang University College of Medicine, Iksan, Korea
| | - Dong Baek Kang
- Department of Surgery, Digestive Disease Research Institute and Institute of Medical Science, Wonkwang University College of Medicine, Iksan, Korea
| | - Won Cheol Park
- Department of Surgery, Digestive Disease Research Institute and Institute of Medical Science, Wonkwang University College of Medicine, Iksan, Korea
| | - Jeong Kyun Lee
- Department of Surgery, Digestive Disease Research Institute and Institute of Medical Science, Wonkwang University College of Medicine, Iksan, Korea
| | - Soo Cheon Chae
- Department of Pathology, Digestive Disease Research Institute and Institute of Medical Science, Wonkwang University College of Medicine, Iksan, Korea
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Kupcinskas J, Wex T, Bornschein J, Selgrad M, Leja M, Juozaityte E, Kiudelis G, Jonaitis L, Malfertheiner P. Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians. BMC MEDICAL GENETICS 2011; 12:112. [PMID: 21864388 PMCID: PMC3166912 DOI: 10.1186/1471-2350-12-112] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/07/2011] [Accepted: 08/24/2011] [Indexed: 12/16/2022]
Abstract
BACKGROUND Several polymorphisms of genes involved in the immunological recognition of Helicobacter pylori and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding Angiotensin converting enzyme (ACE), Nod-like receptor 1 (NOD1), Toll-like receptor 4 (TLR4) and FAS/FASL. METHODS Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. ACE I/D (rs4646994), NOD1 796G>A (rs5743336), TLR4 3725G>C (rs11536889), FAS 1377G>A (rs2234767), FAS 670A>G (rs1800682) and FASL 844T>C (rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis. RESULTS Frequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for NOD1 796G/G genotype to be associated with increased risk of HRAG (62.4% vs. 54.5% in controls, p = 0.082). FAS 670G/G genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (p = 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. NOD1 796G>A and TLR4 3725G>C gene polymorphisms were also not associated with Helicobacter pylori infection. CONCLUSIONS ACE, NOD1, TRL4 and FAS/FASL gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.
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Affiliation(s)
- Juozas Kupcinskas
- Department of Gastroenterology, Lithuanian University of Health Sciences, Eiveniu 2, 50009 Kaunas, Lithuania
| | - Thomas Wex
- Clinic of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
| | - Jan Bornschein
- Clinic of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
| | - Michael Selgrad
- Clinic of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Digestive Diseases Center, Hospital Lizeners, 6 Linezera iela, LV1006 Riga, Latvia
| | - Elona Juozaityte
- Department of Oncology, Lithuanian University of Health Sciences, Eiveniu 2, 50009 Kaunas, Lithuania
| | - Gediminas Kiudelis
- Department of Gastroenterology, Lithuanian University of Health Sciences, Eiveniu 2, 50009 Kaunas, Lithuania
| | - Laimas Jonaitis
- Department of Gastroenterology, Lithuanian University of Health Sciences, Eiveniu 2, 50009 Kaunas, Lithuania
| | - Peter Malfertheiner
- Clinic of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
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He B, Zhang Y, Pan Y, Xu Y, Gu L, Chen L, Wang S. Interleukin 1 beta (IL1B) promoter polymorphism and cancer risk: evidence from 47 published studies. Mutagenesis 2011; 26:637-42. [PMID: 21653279 DOI: 10.1093/mutage/ger025] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Interleukin 1β (IL-1B) is a pro-inflammatory cytokine against infection, playing an important role in the pathogenesis of cancers. The -31T/C polymorphism of the interleukin 1β gene (IL1B) has been implicated in cancer risk through its influence on the IL1B transcription. However, results from studies are conflicting. To clarify the association, a meta-analysis was performed for 11 125 cases and 14 415 controls from 47 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. No significant associations were observed for total cancer from all the comparisons. Through the stratified analyses, there was a statistically significant decreased risk of hepatocellular cancer in carriers of the C allele than non-carriers (CC versus TT: OR = 0.87, 95% CI: 0.77-0.98, P(heterogeneity) = 0.103; TC versus TT: OR = 0.77, 95% CI: 0.62-0.95, P(heterogeneity) = 0.734; TC + CC versus TT: OR = 0.74, 95% CI: 0.61-0.91, P(heterogeneity) = 0.472). Similarly, decreased risk was observed for gastric cancer of the C/C genotype compared with the T/T genotype (OR = 0.87, 95% CI: 0.77-0.98, P(heterogeneity) = 0.103). Using the recessive model, a significantly decreased risk was observed for gastric cancer (OR = 0.88, 95% CI: 0.80-0.97, P(heterogeneity) = 0.158), European population (OR = 0.84, 95% CI: 0.73-0.97, P(heterogeneity) = 0.070) and positive infection-matched studies (OR = 0.75, 95% CI: 0.60-0.94, P(heterogeneity) = 0.220); however, an increased risk was found for breast cancer (OR = 1.34, 95% CI: 1.18-1.61, P(heterogeneity) = 0.116). Although some modest bias could not be eliminated, this meta-analysis suggests that the IL1B -31C allele is a low-penetrance protective factor for the development of cancer, in particular for that associated with infection.
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Affiliation(s)
- Bangshun He
- Central Laboratory, Nanjing First Hospital Affiliated to Nanjing Medical University, 68 Changle Road, Nanjing 210006, Jiangsu, China
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