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Basirinia G, Ali M, Comelli A, Sperandeo A, Piana S, Alongi P, Longo C, Di Raimondo D, Tuttolomondo A, Benfante V. Theranostic Approaches for Gastric Cancer: An Overview of In Vitro and In Vivo Investigations. Cancers (Basel) 2024; 16:3323. [PMID: 39409942 PMCID: PMC11476023 DOI: 10.3390/cancers16193323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 09/24/2024] [Accepted: 09/26/2024] [Indexed: 10/20/2024] Open
Abstract
Gastric cancer (GC) is the second most common cause of cancer-related death worldwide and a serious public health concern. This high death rate is mostly caused by late-stage diagnoses, which lead to poor treatment outcomes. Radiation immunotherapy and targeted therapies are becoming increasingly popular in GC treatment, in addition to surgery and systemic chemotherapy. In this review, we have focused on both in vitro and in vivo research, which presents a summary of recent developments in targeted therapies for gastric cancer. We explore targeted therapy approaches, including integrin receptors, HER2, Claudin 18, and glutathione-responsive systems. For instance, therapies targeting the integrin receptors such as the αvβ3 and αvβ5 integrins have shown promise in enhancing diagnostic precision and treatment efficacy. Furthermore, nanotechnology provides novel approaches to targeted drug delivery and imaging. These include glutathione-responsive nanoplatforms and cyclic RGD peptide-conjugated nanoparticles. These novel strategies seek to reduce systemic toxicity while increasing specificity and efficacy. To sum up, the review addresses the significance of personalized medicine and advancements in gastric cancer-targeted therapies. It explores potential methods for enhancing gastric cancer prognosis and treatment in the future.
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Affiliation(s)
- Ghazal Basirinia
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Molecular and Clinical Medicine, University of Palermo, 90127 Palermo, Italy; (D.D.R.); (A.T.)
- Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy; (G.B.); (M.A.)
| | - Muhammad Ali
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Molecular and Clinical Medicine, University of Palermo, 90127 Palermo, Italy; (D.D.R.); (A.T.)
- Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy; (G.B.); (M.A.)
| | - Albert Comelli
- Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy; (G.B.); (M.A.)
- NBFC—National Biodiversity Future Center, 90133 Palermo, Italy
| | - Alessandro Sperandeo
- Pharmaceutical Factory, La Maddalena S.P.A., Via San Lorenzo Colli, 312/d, 90146 Palermo, Italy; (A.S.); (S.P.)
| | - Sebastiano Piana
- Pharmaceutical Factory, La Maddalena S.P.A., Via San Lorenzo Colli, 312/d, 90146 Palermo, Italy; (A.S.); (S.P.)
| | - Pierpaolo Alongi
- Nuclear Medicine Unit, A.R.N.A.S. Civico Di Cristina e Benfratelli Hospitals, P.zza N. Leotta 4, 90127 Palermo, Italy; (P.A.); (C.L.)
- Advanced Diagnostic Imaging-INNOVA Project, Department of Radiological Sciences, A.R.N.A.S. Civico Di Cristina e Benfratelli Hospitals, P.zza N. Leotta 4, 90127 Palermo, Italy
| | - Costanza Longo
- Nuclear Medicine Unit, A.R.N.A.S. Civico Di Cristina e Benfratelli Hospitals, P.zza N. Leotta 4, 90127 Palermo, Italy; (P.A.); (C.L.)
| | - Domenico Di Raimondo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Molecular and Clinical Medicine, University of Palermo, 90127 Palermo, Italy; (D.D.R.); (A.T.)
| | - Antonino Tuttolomondo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Molecular and Clinical Medicine, University of Palermo, 90127 Palermo, Italy; (D.D.R.); (A.T.)
| | - Viviana Benfante
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Molecular and Clinical Medicine, University of Palermo, 90127 Palermo, Italy; (D.D.R.); (A.T.)
- Advanced Diagnostic Imaging-INNOVA Project, Department of Radiological Sciences, A.R.N.A.S. Civico Di Cristina e Benfratelli Hospitals, P.zza N. Leotta 4, 90127 Palermo, Italy
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Mazurek M, Szewc M, Sitarz MZ, Dudzińska E, Sitarz R. Gastric Cancer: An Up-to-Date Review with New Insights into Early-Onset Gastric Cancer. Cancers (Basel) 2024; 16:3163. [PMID: 39335135 PMCID: PMC11430327 DOI: 10.3390/cancers16183163] [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: 07/23/2024] [Revised: 09/06/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the fifth most common cause of cancer death in the world. Regarding the age at which the diagnosis was made, GC is divided into early-onset gastric cancer (EOGC-up to 45 years of age) and conventional GC (older than 45). EOGC constitutes approximately 10% of all GCs. Numerous reports indicate that EOGC is more aggressive than conventional GC and is often discovered at an advanced tumor stage, which has an impact on the five-year survival rate. The median survival rate for advanced-stage GC is very poor, amounting to less than 12 months. Risk factors for GC include family history, alcohol consumption, smoking, Helicobacter pylori, and Epstein-Barr virus infection. It has been shown that a proper diet and lifestyle can play a preventive role in GC. However, research indicates that risk factors for conventional GC are less correlated with EOGC. In addition, the unclear etiology of EOGC and the late diagnosis of this disease limit the possibilities of effective treatment. Genetic factors are considered a likely cause of EOGC, as young patients are less exposed to environmental carcinogens. Research characterizing GC in young patients is scarce. This comprehensive study presents all aspects: epidemiology, risk factors, new treatment strategies, and future directions.
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Affiliation(s)
- Marek Mazurek
- Department of Surgical Oncology, Masovian Cancer Hospital, 05-135 Wieliszew, Poland;
| | - Monika Szewc
- Department of Normal, Clinical and Imaging Anatomy, Medical University of Lublin, 20-950 Lublin, Poland;
| | - Monika Z. Sitarz
- Department of Conservative Dentistry with Endodontics, Medical University of Lublin, 20-950 Lublin, Poland;
| | - Ewa Dudzińska
- Department of Dietetics and Nutrition Education, Medical University of Lublin, 20-950 Lublin, Poland;
| | - Robert Sitarz
- Department of Normal, Clinical and Imaging Anatomy, Medical University of Lublin, 20-950 Lublin, Poland;
- Department of Surgical Oncology, St. John’s Cancer Center, 20-090 Lublin, Poland
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Kotani S, Shibagaki K, Hirahara N, Hasegawa N, Tanabe R, Ebisutani Y, Nonomura S, Kishimoto K, Kodama Y, Takahashi Y, Kataoka M, Oka A, Fukuba N, Mishima Y, Oshima N, Kawashima K, Ishimura N, Araki A, Kadota K, Itawaki A, Nagasaki M, Miyaoka Y, Onuma H, Ishihara S. Clinicopathologic differences of gastric neoplasms between Helicobacter pylori-infected and -naïve patients: a multicenter retrospective analysis. J Gastroenterol 2024; 59:1-10. [PMID: 37855982 DOI: 10.1007/s00535-023-02050-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 10/01/2023] [Indexed: 10/20/2023]
Abstract
BACKGROUND The incidence of gastric neoplasms in Helicobacter pylori (Hp)-naïve patients has recently increased due to a remarkable decrease in the Hp-infected population in Japan. We investigated the clinicopathologic differences between Hp-infected gastric neoplasms (HpIGNs) and Hp-naïve gastric neoplasms (HpNGNs) that have not been fully elucidated so far. METHODS This retrospective multicenter study investigated 966 consecutive patients with 1131 gastric dysplasia or cancers who underwent endoscopic or surgical treatment for the recent decade. Clinicopathologic features were compared between HpIGN and HpNGN cases. RESULTS One thousand and sixty-eight HpIGNs in 916 patients included 877 differentiated types and 191 undifferentiated types. Sixty-three HpNGNs in 50 patients included 57 differentiated types (35 foveolar types, 15 intestinal types, 6 fundic-gland types, and 1 other differentiated type) and 6 undifferentiated types. HpNGNs occurred in younger (59.5 vs. 71.8 years, p < 0.05) and female patients (40.0% vs. 26.5%, p < 0.05), were found more frequently in the proximal compartment (p < 0.05), and had smaller size (median 4.0 vs. 20.0 mm, p < 0.05). Histologically, HpNGNs and HpIGNs both primarily consisted of differentiated type (90.5% vs. 82.1%, p = 0.089) and HpNGNs showed lower prevalence of invasive cancer (11.1% vs. 37.6%, p < 0.05) and lymphovascular invasion (1.6% vs. 31.6%, p < 0.05). Nearly all HpNGNs (62/63, 98.4%) were diagnosed in early pathological stage, while 16.1% (172/1068) of HpIGNs were diagnosed in advanced stage (p < 0.05). CONCLUSIONS HpNGNs is recently on the increase but shows lower malignant nature regardless of histologic type than HpIGN. Endoscopic gastric cancer screening will be reviewed via cost effectiveness for Hp-naïve individuals in future.
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Affiliation(s)
- Satoshi Kotani
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kotaro Shibagaki
- Department of Endoscopy, Shimane University Hospital, 89-1 Enya, Izumo, 693-8501, Japan.
| | - Noriyuki Hirahara
- Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Nobuaki Hasegawa
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Ryo Tanabe
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yuri Ebisutani
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Saya Nonomura
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kenichi Kishimoto
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yasuhide Kodama
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yusuke Takahashi
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Masatoshi Kataoka
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Akihiko Oka
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Nobuhiko Fukuba
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yoshiyuki Mishima
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Naoki Oshima
- Department of Endoscopy, Shimane University Hospital, 89-1 Enya, Izumo, 693-8501, Japan
| | - Kousaku Kawashima
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Norihisa Ishimura
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Asuka Araki
- Department of Pathology, Shimane University Hospital, Izumo, Japan
| | - Kyuichi Kadota
- Department of Pathology, Shimane University Hospital, Izumo, Japan
| | - Ayako Itawaki
- Department of Gastroenterology, National Hospital Organization Hamada Medical Center, Hamada, Japan
| | - Makoto Nagasaki
- Department of Pathology, National Hospital Organization Hamada Medical Center, Hamada, Japan
| | - Yoichi Miyaoka
- Department of Gastroenterology, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Hideyuki Onuma
- Department of Pathology, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Shunji Ishihara
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
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Ng CS, Ong XJ, Au M, Lau YH, Kwok HHY, Quan J. ALDH2 polymorphism, alcohol intake and the attributable burden of cancer in East Asia: systematic review, meta-analysis, and modeling study. Ann Epidemiol 2023; 85:113-120.e20. [PMID: 37268241 DOI: 10.1016/j.annepidem.2023.05.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Revised: 05/25/2023] [Accepted: 05/25/2023] [Indexed: 06/04/2023]
Abstract
PURPOSE To estimate the burden of alcohol-attributable cancer in East Asian populations accounting for aldehyde dehydrogenase-2 (ALDH2) genotype-specific cancer risk and alcohol exposure. METHODS We conducted a systematic review and meta-analysis of eight databases on cancer risk to derive alcohol dose-response curves by ALDH2 genotype. A simulation-based approach using the Global Burden of Disease (GBD) modeling framework was applied to estimate the population attributable fraction, incidence, and disability-adjusted life-years (DALYs) lost to alcohol-attributable cancer. RESULTS We included 34 studies (66,655 participants) from China, Japan, and South Korea in the meta-analysis. Alcohol dose-response curves for liver, esophageal, and oral cavity/pharynx cancer showed an increased risk for people with the inactivated ALDH2 genetic polymorphism, resulting in a higher burden of alcohol-attributable cancer compared to GBD estimates. Our methods estimated annual incidence of cancer of 230,177 cases, an underestimate of 69,596 cases compared to GBD estimates. Similarly, total DALYs lost annually were underestimated by 1.20 million. CONCLUSIONS The burden of liver, esophageal, and oral cavity/pharynx cancer attributable to alcohol is underestimated in populations with the ALDH2 genetic polymorphism when compared to current estimates.
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Affiliation(s)
- Carmen S Ng
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Xin Jiong Ong
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Minnie Au
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Yan Ho Lau
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Harley H Y Kwok
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Jianchao Quan
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
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Du P, Zhang C, Wang A, Ma Z, Shen S, Li X. Association of Alcohol Drinking and Helicobacter pylori Infection : A Meta-analysis. J Clin Gastroenterol 2023; 57:269-277. [PMID: 34907920 DOI: 10.1097/mcg.0000000000001638] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 10/14/2021] [Indexed: 12/10/2022]
Abstract
BACKGROUND The association between drinking and Helicobacter pylori infection was not clear in the literature. Owing to mixed and inconclusive results, a meta-analysis was conducted to summarize and clarify this association systematically. METHODS Based on a comprehensive search of PubMed, Embase, and Web of Science databases, studies investigating the association between drinking and H. pylori infection were retrieved. We evaluated the strength of this relationship using odds ratios (ORs) with 95% confidence intervals. Sensitivity analysis was also conducted. RESULTS A total of 24 individual studies were included in this meta-analysis. The risk of H. pylori infection was significantly lower in alcohol drinkers than nondrinkers (OR=0.83). People who drink wine (OR=0.90) or mixed types of alcoholic beverages (OR=0.78) had a lower risk of infection compared with those who drink beer. Among people aged 40 years or older, alcohol drinkers had a lower risk of H. pylori infection than nondrinkers (OR=0.68). Among people less than 40 years of age, alcohol drinking was not associated with H. pylori infection risk. Data showed that women were at a lower risk of H. pylori infection than men (OR=0.86). CONCLUSIONS This meta-analysis suggests that the risk of H. pylori infection among alcohol drinkers is lower than that of nondrinkers. Drinking wine and mixed types of alcohol are better at reducing H. pylori infection than drinking beer. Nonetheless, we discourage reducing H. pylori infection through drinking, which increases the risk of other diseases.
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Affiliation(s)
- Pengqiang Du
- Department of Pharmacy, Fuwai Central China Cardiovascular Hospital, Henan Provincial People's Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan Province
| | - Chao Zhang
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing
| | - Aifeng Wang
- Department of Pharmacy, Fuwai Central China Cardiovascular Hospital, Henan Provincial People's Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan Province
| | - Zhichao Ma
- Department of Pharmacy, Affiliated Hospital of Chifeng University, Chifeng, Inner Mongolia, China
| | - Su Shen
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing
| | - Xingang Li
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing
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Im PK, Yang L, Kartsonaki C, Chen Y, Guo Y, Du H, Lin K, Kerosi R, Hacker A, Liu J, Yu C, Lv J, Walters RG, Li L, Chen Z, Millwood IY. Alcohol metabolism genes and risks of site-specific cancers in Chinese adults: An 11-year prospective study. Int J Cancer 2022; 150:1627-1639. [PMID: 35048370 PMCID: PMC7612513 DOI: 10.1002/ijc.33917] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 11/03/2021] [Accepted: 11/15/2021] [Indexed: 12/12/2022]
Abstract
Two genetic variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984, can modify oesophageal cancer risk associated with alcohol consumption in East Asians, but their associations with other cancers remain uncertain. ALDH2-rs671 G>A and ADH1B-rs1229984 G>A were genotyped in 150 722 adults, enrolled from 10 areas in China during 2004 to 2008. After 11 years' follow-up, 9339 individuals developed cancer. Cox regression was used to estimate hazard ratios (HRs) for site-specific cancers associated with these genotypes, and their potential interactions with alcohol consumption. Overall, the A-allele frequency was 0.21 for ALDH2-rs671 and 0.69 for ADH1B-rs1229984, with A-alleles strongly associated with lower alcohol consumption. Among men, ALDH2-rs671 AA genotype was associated with HR of 0.69 (95% confidence interval: 0.53-0.90) for IARC alcohol-related cancers (n = 1900), compared to GG genotype. For ADH1B-rs1229984, the HRs of AG and AA vs GG genotype were 0.80 (0.69-0.93) and 0.75 (0.64-0.87) for IARC alcohol-related cancers, 0.61 (0.39-0.96) and 0.61 (0.39-0.94) for head and neck cancer (n = 196) and 0.68 (0.53-0.88) and 0.60 (0.46-0.78) for oesophageal cancer (n = 546). There were no significant associations of these genotypes with risks of liver (n = 651), colorectal (n = 556), stomach (n = 725) or lung (n = 1135) cancers. Among male drinkers, the risks associated with higher alcohol consumption were greater among ALDH2-rs671 AG than GG carriers for head and neck, oesophageal and lung cancers (Pinteraction < .02). Among women, only 2% drank alcohol regularly, with no comparable associations observed between genotype and cancer. These findings support the causal effects of alcohol consumption on upper aerodigestive tract cancers, with ALDH2-rs671 AG genotype further exacerbating the risks.
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Affiliation(s)
- Pek Kei Im
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Ling Yang
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Christiana Kartsonaki
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Yiping Chen
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Yu Guo
- Chinese Academy of Medical SciencesBeijingChina
| | - Huaidong Du
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Kuang Lin
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Rene Kerosi
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Alex Hacker
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Jingchao Liu
- NCDs Prevention and Control DepartmentWuzhong CDCSuzhouChina
| | - Canqing Yu
- Department of Epidemiology and Biostatistics, School of Public HealthPeking UniversityBeijingChina
| | - Jun Lv
- Department of Epidemiology and Biostatistics, School of Public HealthPeking UniversityBeijingChina
| | - Robin G. Walters
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Liming Li
- Department of Epidemiology and Biostatistics, School of Public HealthPeking UniversityBeijingChina
| | - Zhengming Chen
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Iona Y. Millwood
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
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Gao J, Hao Y, Piao X, Gu X. Aldehyde Dehydrogenase 2 as a Therapeutic Target in Oxidative Stress-Related Diseases: Post-Translational Modifications Deserve More Attention. Int J Mol Sci 2022; 23:ijms23052682. [PMID: 35269824 PMCID: PMC8910853 DOI: 10.3390/ijms23052682] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 02/19/2022] [Accepted: 02/21/2022] [Indexed: 02/07/2023] Open
Abstract
Aldehyde dehydrogenase 2 (ALDH2) has both dehydrogenase and esterase activity; its dehydrogenase activity is closely related to the metabolism of aldehydes produced under oxidative stress (OS). In this review, we recapitulate the enzyme activity of ALDH2 in combination with its protein structure, summarize and show the main mechanisms of ALDH2 participating in metabolism of aldehydes in vivo as comprehensively as possible; we also integrate the key regulatory mechanisms of ALDH2 participating in a variety of physiological and pathological processes related to OS, including tissue and organ fibrosis, apoptosis, aging, and nerve injury-related diseases. On this basis, the regulatory effects and application prospects of activators, inhibitors, and protein post-translational modifications (PTMs, such as phosphorylation, acetylation, S-nitrosylation, nitration, ubiquitination, and glycosylation) on ALDH2 are discussed and prospected. Herein, we aimed to lay a foundation for further research into the mechanism of ALDH2 in oxidative stress-related disease and provide a basis for better use of the ALDH2 function in research and the clinic.
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Affiliation(s)
- Jie Gao
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (J.G.); (Y.H.)
| | - Yue Hao
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (J.G.); (Y.H.)
| | - Xiangshu Piao
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China;
| | - Xianhong Gu
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (J.G.); (Y.H.)
- Correspondence:
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8
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Liu H, Dong Z. Cancer Etiology and Prevention Principle: "1 + X". Cancer Res 2021; 81:5377-5395. [PMID: 34470778 DOI: 10.1158/0008-5472.can-21-1862] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 08/16/2021] [Accepted: 08/31/2021] [Indexed: 11/16/2022]
Abstract
Cancer was previously thought to be an inevitable aspect of human health with no effective treatments. However, the results of in-depth cancer research suggest that most types of cancer may be preventable. Therefore, a comprehensive understanding of the disparities in cancer burden caused by different risk factors is essential to inform and improve cancer prevention and control. Here, we propose the cancer etiology and prevention principle "1 + X," where 1 denotes the primary risk factor for a cancer and X represents the secondary contributing risk factors for the cancer. We elaborate upon the "1 + X" principle with respect to risk factors for several different cancer types. The "1 + X" principle can be used for precise prevention of cancer by eliminating the main cause of a cancer and minimizing the contributing factors at the same time.
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Affiliation(s)
- Hui Liu
- Department of Pathophysiology, School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China
| | - Zigang Dong
- Department of Pathophysiology, School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, China.
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China
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The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment. Acta Pharm Sin B 2021; 11:1400-1411. [PMID: 34221859 PMCID: PMC8245805 DOI: 10.1016/j.apsb.2021.02.008] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 11/29/2020] [Accepted: 12/01/2020] [Indexed: 12/12/2022] Open
Abstract
A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2). The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported. Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types. Furthermore, the ALDH2∗2 polymorphism (rs671) is the most common single nucleotide polymorphism (SNP) in Asia. Epidemiological studies associate ALDH2∗2 with tumorigenesis and progression. This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence, progression, and treatment of tumors in various types of cancer. Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy.
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Key Words
- 4-HNE, 4-hydroxy-2-nonenal
- ALD, alcoholic liver disease
- ALDH2
- ALDH2, aldehyde dehydrogenase 2
- AMPK, AMP-activated protein kinase
- Acetaldehyde
- BCa, bladder cancer
- COUP-TF, chicken ovalbumin upstream promoter-transcription factor
- CRC, colorectal cancer
- CSCs, cancer stem cells
- Cancer
- Cancer therapy
- DFS, disease-free survival
- EC, esophageal cancer
- FA, Fanconi anemia
- FANCD2, Fanconi anemia protein
- GCA, gastric cancer
- HCC, hepatocellular carcinoma
- HDACs, histone deacetylases
- HNC, head and neck cancer
- HNF-4, hepatocyte nuclear factor 4
- HR, homologous recombination
- LCSCs, liver cancer stem cells
- MDA, malondialdehyde
- MDR, multi-drug resistance
- MN, micronuclei
- Metastasis
- NAD, nicotinamide adenine dinucleotide
- NCEs, normochromic erythrocytes
- NER, nucleotide excision repair pathway
- NF-κB, nuclear factor-κB
- NHEJ, non-homologous end-joining
- NRF2, nuclear factor erythroid 2 (NF-E2)-related factor 2
- NRRE, nuclear receptor response element
- NSCLC, non-small-cell lung
- NeG, 1,N2-etheno-dGuo
- OPC, oropharyngeal cancer
- OS, overall survival
- OvCa, ovarian cancer
- PBMC, peripheral blood mononuclear cell
- PC, pancreatic cancer
- PdG, N2-propano-2′-deoxyguanosine
- Polymorphism
- Progression
- REV1, Y-family DNA polymerase
- SCC, squamous cell carcinoma
- TGF-β, transforming growth factor β
- Tumorigenesis
- VHL, von Hippel-Lindau
- ccRCC, clear-cell renal cell carcinomas
- εPKC, epsilon protein kinase C
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Yang K, Lu L, Liu H, Wang X, Gao Y, Yang L, Li Y, Su M, Jin M, Khan S. A comprehensive update on early gastric cancer: defining terms, etiology, and alarming risk factors. Expert Rev Gastroenterol Hepatol 2021; 15:255-273. [PMID: 33121300 DOI: 10.1080/17474124.2021.1845140] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Early gastric cancer (EGC) is a well-defined gastric malignancy that is limited to the mucosa or submucosa, irrespective of lymph node metastasis. At an early stage, gastric cancer often does not cause symptoms until it becomes advanced, and it is a heterogeneous disease and usually encountered in its late stages. AREA COVERED This comprehensive review will provide a novel insight into the evaluation of EGC epidemiology, defining terms, extensive etiology and risk factors, and timely diagnosis since prevention is an essential approach for controlling this cancer and reducing its morbidity and mortality. EXPERT OPINION The causative manner of EGC is complex and multifactorial. In recent years, researchers have made significant contributions to understanding the etiology and pathogenesis of EGC, and standardization in the evaluation of disease activity. Though the incidence of this cancer is steadily declining in some advanced societies owing to appropriate interventions, there remains a serious threat to health in developing nations. Early detection of resectable gastric cancer is crucial for better patient outcomes.
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Affiliation(s)
- Kuo Yang
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Lijie Lu
- Department of Digestive Diseases, Dongfang Hospital of Beijing University of Chinese Medicine , Beijing, PR, China
| | - Huayi Liu
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Xiujuan Wang
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Ying Gao
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Liu Yang
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Yupeng Li
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Meiling Su
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Ming Jin
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Samiullah Khan
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital , Tianjin, PR, China
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11
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Du XY, Wen L, Hu YY, Deng SQ, Xie LC, Jiang GB, Yang GL, Niu YM. Association Between the Aldehyde Dehydrogenase-2 rs671 G>A Polymorphism and Head and Neck Cancer Susceptibility: A Meta-Analysis in East Asians. Alcohol Clin Exp Res 2021; 45:307-317. [PMID: 33283290 DOI: 10.1111/acer.14527] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 11/23/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Aldehyde dehydrogenase-2 (ALDH2) plays an important role in the alcohol detoxification and acetaldehyde metabolism. Published studies have demonstrated some inconsistent associations between ALDH2 rs671 G>A polymorphism and head and neck cancer (HNC) risk. METHODS A meta-analysis was performed to provide pooled data on the association between the ALDH2 rs671 G>A polymorphism and HNC risk. Electronic databases were searched to identify relevant studies. Odds ratios and 95% confidence intervals (CIs) were used to examine the pooled effect size of each genetic model. In addition, heterogeneity test, accumulative analysis, sensitivity analysis, and publication bias were conducted to test the statistical power. RESULTS Thirteen publications (14 independent case-control studies) involving 10,939 subjects were selected. The stratified analysis indicated that both light/moderated drinking (e.g., GA vs. GG: OR = 1.47, 95% CI = 1.16 to 1.86, p < 0.01, I2 = 81.1%) and heavy drinking would increase HNC risk with rs671 G>A mutation (e.g., GA vs. GG: OR = 2.30, 95% CI = 1.11 to 4.77, p = 0.03, I2 = 81.9%). CONCLUSIONS In summary, this meta-analysis suggested that the ALDH2 rs671 G>A polymorphism may play an important synergistic effect in the pathogenesis of HNC development in East Asians.
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Affiliation(s)
- Xin-Ya Du
- From the, Department of Stomatology, (X-YD, G-LY, Y-MN), The People's Hospital of Longhua Shenzhen, Affiliated Longhua People's Hospital, Southern Medicine University, Shenzhen, China
| | - Li Wen
- Department of Dermatology, (LW), Suizhou Hospital, Hubei University of Medicine, Suizhou, China
| | - Yuan-Yuan Hu
- Department of Stomatology, (Y-YH, L-CX, Y-MN), Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China.,Department of Research Affair Management, (Y-YH, S-QD), Gongli Hospital, the Secondary Military Medical University, Shanghai, China.,Department of Radiology and Stomatology, (Y-YH, G-BJ), Suizhou Hospital, Hubei University of Medicine, Suizhou, China
| | - Sheng-Qiong Deng
- Department of Research Affair Management, (Y-YH, S-QD), Gongli Hospital, the Secondary Military Medical University, Shanghai, China
| | - Long-Chuan Xie
- Department of Stomatology, (Y-YH, L-CX, Y-MN), Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China
| | - Guang-Bin Jiang
- Department of Radiology and Stomatology, (Y-YH, G-BJ), Suizhou Hospital, Hubei University of Medicine, Suizhou, China
| | - Gong-Li Yang
- From the, Department of Stomatology, (X-YD, G-LY, Y-MN), The People's Hospital of Longhua Shenzhen, Affiliated Longhua People's Hospital, Southern Medicine University, Shenzhen, China.,Department of Gastroenterology, (G-Li Y), Shenzhen University General Hospital, Shenzhen University, Shenzhen, China
| | - Yu-Ming Niu
- From the, Department of Stomatology, (X-YD, G-LY, Y-MN), The People's Hospital of Longhua Shenzhen, Affiliated Longhua People's Hospital, Southern Medicine University, Shenzhen, China.,Department of Stomatology, (Y-YH, L-CX, Y-MN), Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China
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12
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Joo Kang S, Shin CM, Sung J, Kim N. Association Between ALDH2 Polymorphism and Gastric Cancer Risk in Terms of Alcohol Consumption: A Meta-Analysis. Alcohol Clin Exp Res 2020; 45:6-14. [PMID: 33170513 DOI: 10.1111/acer.14508] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 11/02/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND Alcohol may increase gastric cancer risk. Alcohol can be more carcinogenic in persons who possess inactive ALDH2. The aim of this meta-analysis was to evaluate whether ALDH2 polymorphism can affect alcohol-induced gastric carcinogenesis. METHODS We searched the PubMed, EMBASE, and Cochrane databases to identify relevant articles published between January 2000 and September 2019. Eligible articles were selected according to inclusion and exclusion criteria. The data were analyzed using Review Manager 5.3. RESULTS A total of 7 case-control studies on ALDH2 rs671 polymorphism consisting of 3,251 gastric cancer cases and 4,943 controls were included in the analysis. Inactive ALDH2 genotypes (G/A or A/A) were associated with an increased risk of gastric cancer (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.04 to 1.52, p = 0.02, I2 = 64%), compared with active ALDH2 (G/G genotype). Subgroup analysis by alcohol consumption showed that inactive ALDH2 increased risk for gastric cancer in moderate to heavy drinkers (OR = 1.85, 95% CI: 1.52 to 2.25, p < 0.01, I2 = 6%) more than in nondrinkers or mild drinkers (OR = 1.19; 95% CI: 1.05 to 1.36, p < 0.01, I2 = 6%). Moderate/heavy alcohol consumption increased gastric cancer risk in individuals with inactive ALDH2 (OR = 2.23, 95% CI: 1.63 to 3.05, p < 0.01, I2 = 30%) more than those with active ALDH2 (OR = 1.40, 95% CI: 0.98 to 2.01, p = 0.07, I2 = 85%). CONCLUSIONS The ALDH2 polymorphism modifies the risk of gastric cancer. Moderate/heavy drinkers are more susceptible to gastric cancer than non-drinkers or light drinkers with inactive ALDH2.
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Affiliation(s)
- Seung Joo Kang
- From the, Department of Internal Medicine, (SJK), Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea
| | - Cheol Min Shin
- Department of Internal Medicine, (CMS, NK), Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Joohon Sung
- School of Public Health and Institute of Health and Environment, (JS), Seoul National University, Seoul, Korea
| | - Nayoung Kim
- Department of Internal Medicine, (CMS, NK), Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.,Department of Internal Medicine and Liver Research Institute, (NK), Seoul National University College of Medicine, Seoul, Korea
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13
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Kim K, Chang Y, Ahn J, Yang HJ, Ryu S. Low Levels of Alcohol Consumption and Risk of Intestinal Metaplasia: A Cohort Study. Cancer Epidemiol Biomarkers Prev 2020; 29:2633-2641. [PMID: 32928931 DOI: 10.1158/1055-9965.epi-20-0858] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 07/29/2020] [Accepted: 09/09/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The impact of alcohol drinking on gastric precancerous lesions remains unclear. We investigated the relationship of alcohol intake with risk of atrophic gastritis (AG) and intestinal metaplasia (IM). METHODS This study included 202,675 Korean adults free from AG and IM on their initial endoscopy who were followed with repeated endoscopic examinations. A parametric proportional hazards model was used to estimate the adjusted HR (aHR) with 95% confidence interval (CI) for incident AG and IM based on endoscopic diagnosis. RESULTS During a mean follow-up of 4.7 years, 64,853 incident AG cases and 4,536 IM cases were identified. Alcohol consumption including drinking frequency, quantity, and binge drinking were consistently associated with increased risk of both AG and IM in a dose-response manner. After adjustment for confounders, the multivariable aHRs (95% CIs) for incident IM comparing average alcohol intake of <10, 10-<20, 20-<40, and ≥40 g/day with lifetime abstainers were 1.27 (1.02-1.56), 1.34 (1.07-1.66), 1.50 (1.20-1.86), and 1.54 (1.23-1.93), respectively. Former drinkers were also at a higher risk for AG and IM compared with lifetime abstainers. These associations were consistently observed in never smokers and in time-dependent analyses. CONCLUSIONS In a large cohort of Korean individuals, alcohol intake even at low levels was independently associated with increased risk of developing endoscopic AG and IM, supporting a role of alcohol consumption in the pathogenesis of AG and IM, the precursor lesions of stomach cancer. IMPACT Alcohol consumption from low-level drinking may contribute to gastric carcinogenesis.
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Affiliation(s)
- Kyungeun Kim
- Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoosoo Chang
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. .,Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, Korea
| | - Jiin Ahn
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seungho Ryu
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. .,Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, Korea
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14
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Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies. Int J Mol Sci 2020; 21:4012. [PMID: 32512697 PMCID: PMC7312039 DOI: 10.3390/ijms21114012] [Citation(s) in RCA: 805] [Impact Index Per Article: 161.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 05/31/2020] [Accepted: 06/01/2020] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens. Carcinogenesis is a multistage disease process specified by the progressive development of mutations and epigenetic alterations in the expression of various genes, which are responsible for the occurrence of the disease.
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Affiliation(s)
- Julita Machlowska
- Center for Medical Genomics OMICRON, Jagiellonian University Medical College, 31-034 Kraków, Poland;
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
| | - Jacek Baj
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
| | - Monika Sitarz
- Department of Conservative Dentistry with Endodontics, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Ryszard Maciejewski
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
| | - Robert Sitarz
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
- Department of Surgery, Center of Oncology of the Lublin Region St. Jana z Dukli, 20-090 Lublin, Poland
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15
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Choi CK, Kweon SS, Cho SH, Kim HY, Shin MH. Association between ALDH2 Polymorphism and Gastric Cancer Risk in a Korean Population. J Korean Med Sci 2020; 35:e148. [PMID: 32356421 PMCID: PMC7200175 DOI: 10.3346/jkms.2020.35.e148] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 03/26/2020] [Indexed: 12/24/2022] Open
Abstract
The association between alcohol and gastric cancer is stronger in East Asians than in other ethnic groups, presumably due to an aldehyde dehydrogenase 2 (ALDH2) polymorphism. Therefore, we investigated the relationship between the ALDH2 rs671 polymorphism and gastric cancer in a Korean population. This case-control study included 3,245 hospital patients newly diagnosed with gastric cancer and 8,732 population controls. The ALDH2 rs671 genotype was classified as inactive ALDH2 (GG) or active ALDH2 (GA/AA). The risk of gastric cancer was higher in men with the inactive ALDH2 than in those with active ALDH2 (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09-1.39), whereas no significant association was found between ALDH2 genotype and gastric cancer in women (OR, 1.00; 95% CI, 0.99-1.02). In men, the association between ALDH2 genotype and gastric cancer was stronger in current drinkers. Our findings support the previously reported association between inactive ALDH2 and high risk of gastric cancer.
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Affiliation(s)
- Chang Kyun Choi
- Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea
| | - Sun Seog Kweon
- Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea
| | - Sang Hee Cho
- Department of Hemato-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea
| | - Hye Yeon Kim
- Gwangju-Jeonnam Regional Cardiocerebrovascular Center, Chonnam National University Hospital, Gwangju, Korea
| | - Min Ho Shin
- Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea.
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16
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Cornelis MC. Genetic determinants of beverage consumption: Implications for nutrition and health. ADVANCES IN FOOD AND NUTRITION RESEARCH 2019; 89:1-52. [PMID: 31351524 PMCID: PMC7047661 DOI: 10.1016/bs.afnr.2019.03.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Beverages make important contributions to nutritional intake and their role in health has received much attention. This review focuses on the genetic determinants of common beverage consumption and how research in this field is contributing insight to what and how much we consume and why this genetic knowledge matters from a research and public health perspective. The earliest efforts in gene-beverage behavior mapping involved genetic linkage and candidate gene analysis but these approaches have been largely replaced by genome-wide association studies (GWAS). GWAS have identified biologically plausible loci underlying alcohol and coffee drinking behavior. No GWAS has identified variants specifically associated with consumption of tea, juice, soda, wine, beer, milk or any other common beverage. Thus far, GWAS highlight an important behavior-reward component (as opposed to taste) to beverage consumption which may serve as a potential barrier to dietary interventions. Loci identified have been used in Mendelian randomization and gene×beverage interaction analysis of disease but results have been mixed. This research is necessary as it informs the clinical relevance of SNP-beverage associations and thus genotype-based personalized nutrition, which is gaining interest in the commercial and public health sectors.
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Affiliation(s)
- Marilyn C Cornelis
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
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17
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Abstract
Numerous studies have investigated the association between ALDH2 gene rs671G>A polymorphism and various cancer type in Asians. However, the results remain inconclusive.We conducted a comprehensive meta-analysis including 63 articles with 66 studies containing 25,682 cases and 47,455 controls retrieved by searching PubMed and Embase electronic databases up to March 5, 2018.Pooled results indicated that ALDH2 gene rs671 polymorphism was significantly associated with the overall cancer risk in Asians (homozygous model: odds ratio [OR] = 0.85, 95% confidence interval [CI] = 0.72-0.99, P = .042; heterozygous model: OR = 1.32, 95% CI = 1.14-1.52, P < .001; recessive model: OR = 0.73, 95% CI = 0.60-0.88, P = .001; dominant model: OR = 1.32, 95% CI = 1.16-1.51, P < .001; and allele comparison model: OR = 1.11, 95% CI = 1.03-1.19, P = .004), especially in esophageal cancer and among the Chinese and the Japanese.Our results suggest that ALDH2 rs671 polymorphism is associated with the overall cancer risk in Asians. Well-designed prospective studies with more information about gene-environment interaction, such as drinking, should be conducted to validate our findings.
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Affiliation(s)
| | | | - Lin Ma
- Department of Respiration
| | | | - Shanggan Zeng
- Department of Thoracic Surgery, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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18
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Yang M, Zhang Y, Ren J. ALDH2 Polymorphism and Ethanol Consumption: A Genetic-Environmental Interaction in Carcinogenesis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1193:229-236. [DOI: 10.1007/978-981-13-6260-6_14] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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19
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Yun KE, Chang Y, Yun SC, Davey Smith G, Ryu S, Cho SI, Chung EC, Shin H, Khang YH. Alcohol and coronary artery calcification: an investigation using alcohol flushing as an instrumental variable. Int J Epidemiol 2018; 46:950-962. [PMID: 28073952 DOI: 10.1093/ije/dyw237] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/27/2016] [Indexed: 01/21/2023] Open
Abstract
Background We examined whether alcohol flushing could be used as an instrumental variable (IV) and investigated the effect of alcohol consumption on coronary calcification using alcohol flushing status as an IV. Methods We analysed cross-sectional data from 24 681 Korean adults (20 696 men and 3985 women) who had been administered a questionnaire assessing alcohol consumption and alcohol flushing, as well as a coronary artery calcium (CAC) measurement. The associations of alcohol flushing status with potential confounders and alcohol consumption were examined. We employed two-stage predictor substitution methodology for the IV analysis. Results The prevalence of alcohol flushing did not differ depending on gender, education, household income, cigarette smoking or physical activity. Balanced levels of confounders were observed between alcohol flushers and non-flushers. Alcohol flushing was closely related to alcohol consumption and levels of liver enzymes. In men, a doubling in alcohol consumption was associated with increased odds of coronary calcification in both the IV analysis [odds ratio (OR) of CAC scores of 1 or over = 1.11; 95% confidence interval (CI) = 1.03-1.20) and the multivariable regression analysis (OR = 1.04; 95% CI = 1.01-1.07). For cardiovascular risk factors, the IV analysis showed a positive association between alcohol consumption and blood pressure and high-density lipoprotein-cholesterol. Conclusions Alcohol flushing can be used as an IV in studies evaluating the health impact of alcohol consumption, especially in East Asian countries. Through such an analysis, we found that increased alcohol consumption was associated with an increased risk of subclinical coronary atherosclerosis.
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Affiliation(s)
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center.,Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sung-Cheol Yun
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - George Davey Smith
- MRC Integrative Epidemiology Unit.,School of Social and Community Medicine, University of Bristol, Bristol, UK
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center.,Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sung-Il Cho
- Department of Epidemiology, Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea
| | | | - Hocheol Shin
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Young-Ho Khang
- Department of Health Policy and Management, Seoul National University College of Medicine, and Institute of Health Policy and Management, Seoul National University Medical Research Center, Seoul, South Korea
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20
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Ishioka K, Masaoka H, Ito H, Oze I, Ito S, Tajika M, Shimizu Y, Niwa Y, Nakamura S, Matsuo K. Association between ALDH2 and ADH1B polymorphisms, alcohol drinking and gastric cancer: a replication and mediation analysis. Gastric Cancer 2018; 21:936-945. [PMID: 29616362 DOI: 10.1007/s10120-018-0823-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 03/29/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde accumulation after alcohol drinking. To date, however, evidence for a significant ALDH2-alcohol drinking interaction and a mediation effect of ALDH2/ADH1B through alcohol drinking on gastric cancer have remained unclear. We conducted two case-control studies to validate the interaction and to estimate the mediation effect on gastric cancer. METHODS We calculated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2/ADH1B genotypes and alcohol drinking using conditional logistic regression models after adjustment for potential confounding in the HERPACC-2 (697 cases and 1372 controls) and HERPACC-3 studies (678 cases and 678 controls). We also conducted a mediation analysis of the combination of the two studies to assess whether the effects of these polymorphisms operated through alcohol drinking or through other pathways. RESULTS ALDH2 Lys alleles had a higher risk with increased alcohol consumption compared with ALDH2 Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04-6.27; P for trend = 0.007), indicating a significant ALDH2-alcohol drinking interaction (Pinteraction = 0.024). The mediation analysis indicated a significant positive direct effect (OR 1.67; 95% CI 1.38-2.03) and a protective indirect effect (OR 0.84; 95% CI 0.76-0.92) of the ALDH2 Lys alleles with the ALDH2-alcohol drinking interaction. No significant association of ADH1B with gastric cancer was observed. CONCLUSION The observed ALDH2-alcohol drinking interaction and the direct effect of ALDH2 Lys alleles may suggest the involvement of acetaldehyde in the development of gastric cancer.
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Affiliation(s)
- Kuka Ishioka
- Department of Pathology and Clinical Laboratories, Nagoya University Graduate School of Medicine, Nagoya, Japan.,Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan
| | - Hiroyuki Masaoka
- Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.,Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hidemi Ito
- Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.,Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Isao Oze
- Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan
| | - Seiji Ito
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Masahiro Tajika
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yasuhiro Shimizu
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yasumasa Niwa
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Shigeo Nakamura
- Department of Pathology and Clinical Laboratories, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Keitaro Matsuo
- Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. .,Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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Wang S, Freedman ND, Loftfield E, Hua X, Abnet CC. Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric noncardia adenocarcinoma: A 16-year prospective analysis from the NIH-AARP diet and health cohort. Int J Cancer 2018; 143:2749-2757. [PMID: 29992560 DOI: 10.1002/ijc.31740] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Revised: 05/30/2018] [Accepted: 06/21/2018] [Indexed: 12/13/2022]
Abstract
The role of alcoholic beverages in the etiology of gastric cancer is unclear. Recent summaries showed a positive association between higher alcohol intake and gastric cancer risk, but the magnitude of association is small, there is moderate heterogeneity among studies, and most cases were from Asian populations. We prospectively investigated the associations of alcohol consumption with gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in 490,605 adults, aged 50-71 years at baseline who participated in the NIH-AARP diet and health study. Alcohol consumption in the past year was assessed at baseline by questionnaire and defined as total grams of ethanol intake per day or as a categorical variable: nondrinker, up to or including one drink per day, one to three drinks per day and greater than three drinks per day. We used multivariable-adjusted Cox proportional hazards regression to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for associations between alcohol intake and risk of gastric adenocarcinomas. Through 2011, 662 incident cases of GCA and 713 of GNCA occurred. We found no association between higher alcohol consumption and GCA or GNCA, when examined as total alcoholic beverage intake or individual beverage types of beer, wine and liquor. Furthermore, we observed no association by stratum of sex, ethnic group, educational level or smoking status. We did, however, observe lower risk of GNCA among participants who drank up to one drink per day (HR = 0.81, 95% CI: 0.67-0.97) compared to nondrinkers. In conclusion, alcohol consumption was not associated with increased risk of GCA or GNCA in this large U.S. cohort.
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Affiliation(s)
- ShaoMing Wang
- National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD
| | - Neal D Freedman
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD
| | - Erikka Loftfield
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD
| | - Xing Hua
- Biostatistics Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD
| | - Christian C Abnet
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD
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22
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Lv Z, Sun L, Xu Q, Gong Y, Jing J, Dong N, Xing C, Yuan Y. SNP interactions of PGC with its neighbor lncRNAs enhance the susceptibility to gastric cancer/atrophic gastritis and influence the expression of involved molecules. Cancer Med 2018; 7:5252-5271. [PMID: 30155999 PMCID: PMC6198214 DOI: 10.1002/cam4.1743] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 07/29/2018] [Accepted: 07/30/2018] [Indexed: 12/11/2022] Open
Abstract
Multidimensional interactions of multiple factors are more important in promoting cancer initiation. Gene-gene interactions between protein-coding genes have been paid great attention, while rare studies refer to the interactions between encoding and noncoding genes. Our research group previously found encoding gene PGC polymorphisms could affect the susceptibility to atrophic gastritis (AG) and gastric cancer (GC). Interestingly, several SNPs in long noncoding RNA (lncRNA) genes, just adjacent to PGC, were found to be associated with AG risk and GC prognosis afterward. This study aims to explore the SNP interactions between PGC and its neighbor lncRNAs on the risk of AG and GC. Genotyping for seven PGC SNPs and seven lncRNA SNPs was conducted using Sequenom MassARRAY platform in a total of 2228 northern Chinese subjects, including 536 GC cases, 810 AG cases, and 882 controls. We found 15 pairwise PGC-lncRNAs SNPs had interactions: Five pairs were associated with AG risk, and ten pairs were associated with GC risk. Moreover, two GC-related interactions PGC rs6939861 with lnc-C6orf-132-1 rs7749023 and rs7747696 survived the Bonferroni correction (Pcorrection = 0.049 and 0.007, respectively). Several combinations showed obvious epistasis and cumulative effects on disease risk. Some three-way interactions of SNPs with smoking and drinking could also be observed. Besides, a few interacting SNPs showed correlations with the expression levels of PGC protein and related lncRNAs in serum. Our study would provide research clues for further screening combination biomarkers uniting both protein-coding and noncoding genes with the potential in prediction of the susceptibility to GC and its precursor.
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Affiliation(s)
- Zhi Lv
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryChina Medical University First HospitalShenyangChina
- The Key Laboratory of Cancer Etiology and PreventionLiaoning Provincial Education DepartmentChina Medical UniversityShenyangChina
| | - Liping Sun
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryChina Medical University First HospitalShenyangChina
- The Key Laboratory of Cancer Etiology and PreventionLiaoning Provincial Education DepartmentChina Medical UniversityShenyangChina
| | - Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryChina Medical University First HospitalShenyangChina
- The Key Laboratory of Cancer Etiology and PreventionLiaoning Provincial Education DepartmentChina Medical UniversityShenyangChina
| | - Yuehua Gong
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryChina Medical University First HospitalShenyangChina
- The Key Laboratory of Cancer Etiology and PreventionLiaoning Provincial Education DepartmentChina Medical UniversityShenyangChina
| | - Jingjing Jing
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryChina Medical University First HospitalShenyangChina
- The Key Laboratory of Cancer Etiology and PreventionLiaoning Provincial Education DepartmentChina Medical UniversityShenyangChina
| | - Nannan Dong
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryChina Medical University First HospitalShenyangChina
- The Key Laboratory of Cancer Etiology and PreventionLiaoning Provincial Education DepartmentChina Medical UniversityShenyangChina
| | - Chengzhong Xing
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryChina Medical University First HospitalShenyangChina
- The Key Laboratory of Cancer Etiology and PreventionLiaoning Provincial Education DepartmentChina Medical UniversityShenyangChina
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryChina Medical University First HospitalShenyangChina
- The Key Laboratory of Cancer Etiology and PreventionLiaoning Provincial Education DepartmentChina Medical UniversityShenyangChina
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23
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Gastric cancer may share genetic predisposition with esophageal squamous cell carcinoma in Chinese populations. J Hum Genet 2018; 63:1159-1168. [DOI: 10.1038/s10038-018-0501-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 07/15/2018] [Accepted: 07/31/2018] [Indexed: 02/07/2023]
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24
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Zhong Z, Hou J, Li B, Zhang Q, Li C, Liu Z, Yang M, Zhong W, Zhao P. Genetic Polymorphisms of the Mitochondrial Aldehyde Dehydrogenase ALDH2 Gene in a Large Ethnic Hakka Population in Southern China. Med Sci Monit 2018; 24:2038-2044. [PMID: 29623947 PMCID: PMC5903313 DOI: 10.12659/msm.906606] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Human mitochondrial aldehyde dehydrogenase 2 (ALDH2) plays a critical role in the detoxification of the ethanol metabolite acetaldehyde. The ALDH2*2 (rs671) gene variant is mainly absent among Europeans but is prevalent in populations in East Asia. The aim of this study was to investigate ALDH2*2 mutant alleles and genotype frequencies in the Hakka population of China. Material/Methods Between January 2016 and June 2017, 7,966 unrelated individuals were recruited into the study from the Hakka ethnic population residing in the Meizhou area of Guangdong Province, China, who provided venous blood samples. Genotyping of ALDH2 genotypes were determined using a gene chip platform and confirmed by DNA sequencing. Results In the 7,966 individuals from the Hakka population of China in this study, the frequencies of the ALDH2 genotypes *1/*1, *1/*2 and *2/*2 were 52.03%, 39.67%, and 8.30%, respectively; 47.97% of the individuals were found to carry the ALDH2*2 genotype, which was associated with a deficiency in the aldehyde dehydrogenase (ALDH2) enzyme activity. The frequency of the ALDH2*2 allele was lower than that previously reported in the Japanese population but higher than that reported in other Oriental populations. Conclusions The findings of this study have provided new information on the ALDH2 gene polymorphisms in the Hakka ethnic population residing in the Meizhou area of Guangdong Province, China, including an understanding of the origin of the atypical ALDH2*2 allele. Also, the study findings may be relevant to the primary care of patients in China.
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Affiliation(s)
- Zhixiong Zhong
- Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland).,Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland)
| | - Jingyuan Hou
- Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland).,Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland)
| | - Bin Li
- Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland)
| | - Qifeng Zhang
- Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland)
| | - Cunren Li
- Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland)
| | - Zhidong Liu
- Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland)
| | - Min Yang
- Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland)
| | - Wei Zhong
- Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland)
| | - Pingsen Zhao
- Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland).,Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, Guangdong, China (mainland)
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25
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Yang S, Lee J, Choi IJ, Kim YW, Ryu KW, Sung J, Kim J. Effects of alcohol consumption, ALDH2 rs671 polymorphism, and Helicobacter pylori infection on the gastric cancer risk in a Korean population. Oncotarget 2018; 8:6630-6641. [PMID: 28036260 PMCID: PMC5351658 DOI: 10.18632/oncotarget.14250] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 12/05/2016] [Indexed: 12/22/2022] Open
Abstract
The effect of alcohol consumption on the risk of gastric cancer (GC) has not yet been fully elucidated, and an aldehyde dehydrogenase 2 (ALDH2) polymorphism, rs671, is a genetic variant that influences alcohol consumption in East Asians. Additionally, the discrepancy between the Helicobacter pylori (H. pylori) infection prevalence and GC incidence across Asian countries has not been explained. This study evaluated the effects of alcohol consumption and genetic susceptibility to defective acetaldehyde metabolism on the GC risk and their interactions with H. pylori infection. This study included 450 Korean GC cases and 1,050 controls recruited at the National Cancer Center. Data for 795 patients and 4,893 controls were used for further confirmation of the effect of rs671. Increased GC risks were evident for rs671 A allele carriers (odds ratio (OR), 1.23; 95% confidence interval (CI), 1.08-1.41) and H. pylori-infected individuals (OR, 7.07; 95% CI, 4.60-10.86), but no dose-response association with alcohol consumption was observed. Furthermore, the interactions between these factors were not significant. This study has demonstrated that alcohol consumption and rs671 should be considered simultaneously when assessing the GC risk. Additionally, alcohol-related factors were not found to interact with H. pylori infection, and further studies evaluating other environmental factors are required to explain the Asian enigma.
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Affiliation(s)
- Sarah Yang
- Molecular Epidemiology Branch, Division of Cancer Epidemiology and Prevention, National Cancer Center, Goyang, Korea.,Complex Disease & Genome Epidemiology Branch, Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Jeonghee Lee
- Molecular Epidemiology Branch, Division of Cancer Epidemiology and Prevention, National Cancer Center, Goyang, Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea
| | - Young Woo Kim
- Center for Gastric Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea.,Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Keun Won Ryu
- Center for Gastric Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea
| | - Joohon Sung
- Complex Disease & Genome Epidemiology Branch, Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Jeongseon Kim
- Molecular Epidemiology Branch, Division of Cancer Epidemiology and Prevention, National Cancer Center, Goyang, Korea.,Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
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26
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Shin CM, Kim N, Cho SI, Sung J, Lee HJ. Validation of Alcohol Flushing Questionnaires in Determining Inactive Aldehyde Dehydrogenase-2 and Its Clinical Implication in Alcohol-Related Diseases. Alcohol Clin Exp Res 2018; 42:387-396. [PMID: 29205834 DOI: 10.1111/acer.13569] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 11/28/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND Our aim was to validate alcohol flushing questionnaires in detecting inactive ALDH2 (ALDH2*1/*2 or ALDH2*2/*2). METHODS Two study sets were established; in study set 1, 210 healthy male subjects (age 22 to 59 years) were enrolled; in study set 2, 756 subjects were enrolled who received esophagogastroduodenoscopy to evaluate their dyspeptic symptoms or as part of a gastric cancer screening program. Subjects in study sets 1 and 2 completed the modified alcohol flushing questionnaires of Yokoyama and colleagues (, ). Polymerase chain reaction-restriction fragment length polymorphism method was used to determine ALDH2 genotype. RESULTS In study set 1, 29.0% (61 of 210) had inactive ALDH2. The sensitivity and specificity of the modified alcohol flushing questionnaire for detecting inactive ALDH2 were 95.1 and 76.5%, respectively. Drinking problems negatively correlated with positive alcohol flushing response and inactive ALDH2 (all p-values < 0.05). In study set 2, the sensitivity and specificity of the alcohol flushing questionnaire for detecting inactive ALDH2 were 78.9 and 82.1%, respectively. Interestingly, drinking ≥7 units/wk in men or ≥3.5 units/wk in women significantly increased the risk of benign gastric ulcer (BGU) among positive alcohol flushers (odds ratio, 8.97; 95% confidence interval, 1.38 to 58.30), but not among negative alcohol flushers. CONCLUSIONS Simple flushing questionnaires may be administered to the Korean population as a screening tool in detecting individuals who carry inactive ALDH2. Alcohol flushing response negatively correlates with drinking problems and can modify the risk for BGU by alcohol intake.
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Affiliation(s)
- Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sung-Il Cho
- School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, Korea
| | - Joohon Sung
- School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, Korea
| | - Hee-Jung Lee
- Incheon Research Institute of Public Health and Environment , Incheon, Korea
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27
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Ghosh S, Bankura B, Ghosh S, Saha ML, Pattanayak AK, Ghatak S, Guha M, Nachimuthu SK, Panda CK, Maji S, Chakraborty S, Maity B, Das M. Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India. BMC Cancer 2017; 17:782. [PMID: 29166882 PMCID: PMC5700676 DOI: 10.1186/s12885-017-3713-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 10/30/2017] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most frequently diagnosed digestive tract cancers and carries a high risk of mortality. Acetaldehyde (AA), a carcinogenic intermediate of ethanol metabolism contributes to the risk of GC. The accumulation of AA largely depends on the activity of the major metabolic enzymes, alcohol dehydrogenase and aldehyde dehydrogenase encoded by the ADH (ADH1 gene cluster: ADH1A, ADH1B and ADH1C) and ALDH2 genes, respectively. This study aimed to evaluate the association between genetic variants in these genes and GC risk in West Bengal, India. METHODS We enrolled 105 GC patients (cases), and their corresponding sex, age and ethnicity was matched to 108 normal individuals (controls). Genotyping for ADH1A (rs1230025), ADH1B (rs3811802, rs1229982, rs1229984, rs6413413, rs4147536, rs2066702 and rs17033), ADH1C (rs698) and ALDH2 (rs886205, rs968529, rs16941667 and rs671) was performed using DNA sequencing and RFLP. RESULTS Genotype and allele frequency analysis of these SNPs revealed that G allele of rs17033 is a risk allele (A vs G: OR = 3.67, 95% CI = 1.54-8.75, p = 0.002) for GC. Significant association was also observed between rs671 and incidence of GC (p = 0.003). Moreover, smokers having the Lys allele of rs671 had a 7-fold increased risk of acquiring the disease (OR = 7.58, 95% CI = 1.34-42.78, p = 0.009). CONCLUSION In conclusion, rs17033 of ADH1B and rs671 of ALDH2 SNPs were associated with GC risk and smoking habit may further modify the effect of rs671. Conversely, rs4147536 of ADH1B might have a protective role in our study population. Additional studies with a larger patient population are needed to confirm our results.
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Affiliation(s)
- Sudakshina Ghosh
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, West Bengal 700019 India
| | - Biswabandhu Bankura
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, West Bengal 700019 India
| | - Soumee Ghosh
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, West Bengal 700019 India
| | - Makhan Lal Saha
- Department of Surgery, Institute of Post Graduate Medical Education & Research, 244 A.J.C Bose Road, Kolkata, West Bengal 700 020 India
| | - Arup Kumar Pattanayak
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, West Bengal 700019 India
| | - Souvik Ghatak
- Department of Biotechnology, Mizoram University, Tanhril, P.O Box No. 190, Aizawl, Mizoram India
| | - Manalee Guha
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, West Bengal 700019 India
| | - Senthil Kumar Nachimuthu
- Department of Biotechnology, Mizoram University, Tanhril, P.O Box No. 190, Aizawl, Mizoram India
| | - Chinmoy Kumar Panda
- Department of Oncogene Regulation and Viral Associated Human Cancer, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata, West Bengal 700026 India
| | - Suvendu Maji
- Department of Surgery, Institute of Post Graduate Medical Education & Research, 244 A.J.C Bose Road, Kolkata, West Bengal 700 020 India
| | - Subrata Chakraborty
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, West Bengal 700019 India
| | - Biswanath Maity
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, West Bengal 700019 India
| | - Madhusudan Das
- Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, West Bengal 700019 India
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28
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Jiang Y, Zhang J, Wu Y, Wang J, Li L. Association between ALDH2 rs671 G>A polymorphism and gastric cancer susceptibility in Eastern Asia. Oncotarget 2017; 8:102401-102412. [PMID: 29254255 PMCID: PMC5731965 DOI: 10.18632/oncotarget.22060] [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: 08/18/2017] [Accepted: 09/20/2017] [Indexed: 12/20/2022] Open
Abstract
To date, the relationship between the aldehyde dehydrogenases-2 (ALDH2) rs671 G>A (Glu504Lys) polymorphism and gastric cancer (GC) risk has not been thoroughly elucidated. To derive a more precise estimation of the effect of the ALDH2 rs671 G>A polymorphism on GC, we conducted this meta-analysis. We searched for qualified studies in the Embase, PubMed, Wang Fan and China National Knowledge Infrastructure databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association. A total of 6,421 GC patients and 8,832 control subjects were included in the present study. The pooled results indicated no significant relationship between the ALDH2 rs671 G>A polymorphism and GC susceptibility in all genetic models. A stratified analysis by country showed that the ALDH2 rs671 G>A polymorphism might be a risk factor for GC in Japan (Allele model: Punadjusted = 0.034; Dominant model: Punadjusted = 0.040); however, the result was nonsignificant when the Bonferroni correction and false discovery rate (FDR) were applied. In subgroup analyses by drinking status in the dominant model, our study revealed that the ALDH2 rs671 G>A polymorphism significantly increased the risk of GC for drinkers (dominant model: P < 0.001). No relationship between the ALDH2 rs671 G>A polymorphism and GC risk was observed in any other subgroup. Our present study indicated no association between the ALDH2 rs671 G>A polymorphism and GC risk in Eastern Asian populations. However, the ALDH2 rs671 G>A polymorphism can significantly increase GC risk for drinkers.
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Affiliation(s)
- You Jiang
- Department of General Surgery, Hefei Second People's Hospital, Anhui Medical University, Hefei, Anhui, 230011, China
| | - Jun Zhang
- Department of General Surgery, Hefei Second People's Hospital, Anhui Medical University, Hefei, Anhui, 230011, China
| | - Yuee Wu
- Department of Electrocardiogram Diagnosis, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230060, China
| | - Jian Wang
- Department of Pathology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, China
| | - Liang Li
- Department of General Surgery, Hefei Second People's Hospital, Anhui Medical University, Hefei, Anhui, 230011, China
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29
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Rota M, Pelucchi C, Bertuccio P, Matsuo K, Zhang ZF, Ito H, Hu J, Johnson KC, Palli D, Ferraroni M, Yu GP, Muscat J, Lunet N, Peleteiro B, Ye W, Song H, Zaridze D, Maximovitch D, Guevara M, Fernández-Villa T, Vioque J, Navarrete-Muñoz EM, Wolk A, Orsini N, Bellavia A, Håkansson N, Mu L, Persiani R, Kurtz RC, Lagiou A, Lagiou P, Galeone C, Bonzi R, Boffetta P, Boccia S, Negri E, La Vecchia C. Alcohol consumption and gastric cancer risk-A pooled analysis within the StoP project consortium. Int J Cancer 2017; 141:1950-1962. [PMID: 28718913 DOI: 10.1002/ijc.30891] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Revised: 05/22/2017] [Accepted: 05/29/2017] [Indexed: 01/11/2023]
Abstract
An association between heavy alcohol drinking and gastric cancer risk has been recently reported, but the issue is still open to discussion and quantification. We investigated the role of alcohol drinking on gastric cancer risk in the "Stomach cancer Pooling (StoP) Project," a consortium of epidemiological studies. A total of 9,669 cases and 25,336 controls from 20 studies from Europe, Asia and North America were included. We estimated summary odds-ratios (ORs) and the corresponding 95% confidence intervals (CIs) by pooling study-specific ORs using random-effects meta-regression models. Compared with abstainers, drinkers of up to 4 drinks/day of alcohol had no increase in gastric cancer risk, while the ORs were 1.26 (95% CI, 1.08-1.48) for heavy (>4 to 6 drinks/day) and 1.48 (95% CI 1.29-1.70) for very heavy (>6 drinks/day) drinkers. The risk for drinkers of >4 drinks/day was higher in never smokers (OR 1.87, 95% CI 1.35-2.58) as compared with current smokers (OR 1.14, 95% CI 0.93-1.40). Somewhat stronger associations emerged with heavy drinking in cardia (OR 1.61, 95% CI 1.11-2.34) than in non-cardia (OR 1.28, 95% CI 1.13-1.45) gastric cancers, and in intestinal-type (OR 1.54, 95% CI 1.20-1.97) than in diffuse-type (OR 1.29, 95% CI 1.05-1.58) cancers. The association was similar in strata of H. pylori infected (OR = 1.52, 95% CI 1.16-2.00) and noninfected subjects (OR = 1.69, 95% CI 0.95-3.01). Our collaborative pooled-analysis provides definite, more precise quantitative evidence than previously available of an association between heavy alcohol drinking and gastric cancer risk.
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Affiliation(s)
- Matteo Rota
- Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.,Department of Biomedical and Clinical Sciences, University of Milan, Italy
| | - Claudio Pelucchi
- Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.,Department of Clinical Sciences and Community Health, University of Milan, Italy
| | - Paola Bertuccio
- Department of Clinical Sciences and Community Health, University of Milan, Italy
| | - Keitaro Matsuo
- Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Zuo-Feng Zhang
- Department of Epidemiology, UCLA Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, CA
| | - Hidemi Ito
- Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Jinfu Hu
- Department of Epidemiology, Harbin Medical University, Harbin, China
| | - Kenneth C Johnson
- School of Epidemiology, Public Health and Preventive Medicine (SEPHPM), University of Ottawa, ON, Canada
| | - Domenico Palli
- Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-Istituto per lo Studio e la Prevenzione Oncologica (ISPO), Florence, Italy
| | - Monica Ferraroni
- Department of Clinical Sciences and Community Health, University of Milan, Italy
| | - Guo-Pei Yu
- Medical Informatics Center, Peking University, Peking, China
| | - Joshua Muscat
- Department of Public Health Sciences, Tobacco Center of Regulatory Science, Penn Sylvania State University College of Medicine, Hershey, PA
| | - Nuno Lunet
- ISPUP-EPIUnit, Universidade do Porto, Porto, Portugal.,Departamento de Epidemiologia Clínica, Medicina Preditiva e Saúde Pública, Faculdade de Medicina, Universidade do Porto, Portugal
| | - Bárbara Peleteiro
- ISPUP-EPIUnit, Universidade do Porto, Porto, Portugal.,Departamento de Epidemiologia Clínica, Medicina Preditiva e Saúde Pública, Faculdade de Medicina, Universidade do Porto, Portugal
| | - Weimin Ye
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Huan Song
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - David Zaridze
- Department of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Center, Moscow, Russia
| | - Dmitry Maximovitch
- Department of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Center, Moscow, Russia
| | - Marcela Guevara
- Public Health Institute of Navarra, IdiSNA, Pamplona, Spain.,CIBER de Epidemiología y Salud Pública (CIBERESP), Pamplona, Spain
| | - Tania Fernández-Villa
- Research Group on Gene-Environment Interactions (GIGAS), University of Leòn, Leòn, Spain
| | - Jesus Vioque
- CIBER de Epidemiología y Salud Pública (CIBERESP), Pamplona, Spain.,Department of Public Health, Miguel Hernandez University, Campus San Juan, Alicante, Spain
| | - Eva M Navarrete-Muñoz
- CIBER de Epidemiología y Salud Pública (CIBERESP), Pamplona, Spain.,Department of Public Health, Miguel Hernandez University, Campus San Juan, Alicante, Spain
| | - Alicja Wolk
- Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Nicola Orsini
- Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Andrea Bellavia
- Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Niclas Håkansson
- Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Lina Mu
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, NY
| | - Roberto Persiani
- Department of Surgical Sciences, Division of General Surgery, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario "Agostino Gemelli", Rome, Italy
| | - Robert C Kurtz
- Department of Medicine, Memorial Sloan Kettering Cancer Centre, NY
| | - Areti Lagiou
- Department of Public Health and Community Health, School of Health Professions, Athens Technological Educational Institute, Athens, Greece
| | - Pagona Lagiou
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Carlotta Galeone
- Department of Clinical Sciences and Community Health, University of Milan, Italy
| | - Rossella Bonzi
- Department of Clinical Sciences and Community Health, University of Milan, Italy
| | - Paolo Boffetta
- The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, NY
| | - Stefania Boccia
- Section of Hygiene - Institute of Public Health, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario "Agostino Gemelli,", Rome, Italy
| | - Eva Negri
- Department of Biomedical and Clinical Sciences, University of Milan, Italy
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, University of Milan, Italy
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30
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Bae JM, Kim EH. Helicobacter pylori Infection and Risk of Gastric Cancer in Korea: A Quantitative Systematic Review. J Prev Med Public Health 2017; 49:197-204. [PMID: 27499162 PMCID: PMC4977768 DOI: 10.3961/jpmph.16.024] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 07/07/2016] [Indexed: 12/14/2022] Open
Abstract
Objectives: In the context of the global decrease in mortality due to gastric cancer, previous studies have reported that the effect of chronic Helicobacter pylori (H. pylori) infection on the incidence of gastric cancer varies among regions. This systematic review was conducted to investigate H. pylori as a risk factor for gastric cancer in Korea, where the incidence of gastric cancer is among the highest in the world. Methods: A search strategy was established to identify articles published in Korean as well as in English. Ultimately, we included observational studies conducted among Korean patients that designed with an age-matched and sex-matched control group that reported the odds ratio associated with H. pylori. Gastric cancer cases were subdivided into overall (OGC), cardia (CGC), non-cardia (NGC), early (EGC), advanced, intestinal (IGC), and diffuse forms of gastric cancer. Summary odds ratios (SORs) with 95% confidence intervals (CIs) were calculated in the meta-analysis using a random-effect model. Results: Eleven case-control studies were ultimately selected. H. pylori was associated with an SOR of 1.81 (95% CI, 1.29 to 2.54) for OGC. Additionally, statistically significant risks were observed for CGC, NGC, EGC, and IGC. Conclusions: Chronic H. pylori infection was found to raise the risk of gastric cancer among Koreans, with the highest risk observed for CGC and EGC (SOR=2.88 for both). Follow-up clinical epidemiologic studies are needed to assess the effects of current treatments aimed at eradicating H. pylori infections.
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Affiliation(s)
- Jong-Myon Bae
- Department of Preventive Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Eun Hee Kim
- Department of Preventive Medicine, Jeju National University School of Medicine, Jeju, Korea
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Ma K, Baloch Z, He TT, Xia X. Alcohol Consumption and Gastric Cancer Risk: A Meta-Analysis. Med Sci Monit 2017; 23:238-246. [PMID: 28087989 PMCID: PMC5256369 DOI: 10.12659/msm.899423] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 05/18/2016] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND We sought to determine by meta-analysis the relationship between drinking alcohol and the risk of gastric cancer. MATERIAL AND METHODS A systematic Medline search was performed to identify all published reports of drinking alcohol and the associated risk of gastric cancer. Initially we retrieved 2,494 studies, but after applying inclusion and exclusion criteria, only ten studies were found to be eligible for our meta-analysis. RESULTS Our meta-analysis showed that alcohol consumption elevated the risk of gastric cancer with an odds ratio (OR) of 1.39 (95% CI 1.20-1.61). Additionally, subgroup analysis showed that only a nested case-control report from Sweden did not support this observation. Subgroup analysis of moderate drinking and heavy drinking also confirmed that drinking alcohol increased the risk of gastric cancer. Publication bias analysis (Begg's and Egger's tests) showed p values were more than 0.05, suggesting that the 10 articles included in our analysis did not have a publication bias. CONCLUSIONS The results from this meta-analysis support the hypothesis that alcohol consumption can increase the risk of gastric cancer; suggesting that effective moderation of alcohol drinking may reduce the risk of gastric cancer.
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Affiliation(s)
- Ke Ma
- Department of Pharmacology, Medical College of Qingdao University, Qingdao, Shandong, P.R. China
| | - Zulqarnain Baloch
- Viral Gene Lab, College of Veterinary Medicine, South China Agriculture University, Guangzhou, Guangdong, P.R. China
| | - Ting-Ting He
- Department of Pharmacology, Medical College of Qingdao University, Qingdao, Shandong, P.R. China
| | - Xueshan Xia
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China
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32
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Kim HJ, Kim N, Yoon H, Choi YJ, Lee JY, Kwon YH, Yoon K, Jo HJ, Shin CM, Park YS, Park DJ, Kim HH, Lee HS, Lee DH. Comparison between Resectable Helicobacter pylori-Negative and -Positive Gastric Cancers. Gut Liver 2016; 10:212-9. [PMID: 26087794 PMCID: PMC4780450 DOI: 10.5009/gnl14416] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/AIMS Controversy exists regarding the characteristics of Helicobacter pylori infection-negative gastric cancer (HPIN-GC). The aim of this study was to evaluate clinicopathologic features of HPIN-GC compared to H. pylori infection-positive gastric cancer (HPIP-GC) using a comprehensive analysis that included genetic and environmental factors. METHODS H. pylori infection status of 705 resectable gastric cancer patients was determined by the rapid urease test, testing for anti-H. pylori antibodies, histologic analysis and culture of gastric cancer tissue samples, and history of H. pylori eradication. HPIN-GC was defined as gastric cancer that was negative for H. pylori infection based on all five methods and that had no evidence of atrophy in histology or serology. RESULTS The prevalence of HPIN-GC was 4% (28/705). No significant differences with respect to age, sex, smoking, drinking, family history of gastric cancer or obesity were observed between the two groups. HPIN-GC tumors were marginally more likely to involve the cardia (14.3% for HPIN-GC vs 5.3% for HPIP-GC, p=0.068). The Lauren classification, histology, and TNM stage did not differ according to H. pylori infection status. Microsatellite instability was not different between the two groups, but p53 overexpression in HPIN-GC was marginally higher than in HPIP-GC (56.0% for HPIN-GC vs 37.0% for HPIP-GC, p=0.055). CONCLUSIONS The prevalence of HPIN-GC was extremely low, and its clinicopathologic characteristics were similar to HPIP-GC.
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Affiliation(s)
- Hee Jin Kim
- Department of Internal Medicine, Myongji Hospital, Goyang, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ju Yup Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yong Hwan Kwon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kichul Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyun Jin Jo
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyung Ho Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Significant association between decreased ALDH2 activity and increased sensitivity to genotoxic effects in workers occupationally exposed to styrene. Oncotarget 2016; 7:38224-38234. [PMID: 27224914 PMCID: PMC5122384 DOI: 10.18632/oncotarget.9502] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Accepted: 05/01/2016] [Indexed: 12/15/2022] Open
Abstract
ALDH2 is involved in the metabolism of styrene, a widely used industrial material, but no data are available regarding the influence of this enzyme on the metabolic fate as well as toxic effects of this chemical. In this study, we recruited 329 workers occupationally exposed to styrene and 152 unexposed controls. DNA strand breaks, DNA-base oxidation in leukocytes and urinary 8-hydroxydeoxyguanosine (8-OH-dG) were assayed as biomarkers to measure genotoxic effects. Meanwhile, we examined the genetic polymorphisms, including ALDH2, EXPH1, GSTM1, GSTT1 and CYP2E1, and also analyzed the levels of styrene exposure through detecting urinary styrene metabolites and styrene concentration in air. In terms of DNA damage, the three genotoxic biomarkers were significantly increased in exposed workers as compared with controls. And the styrene-exposed workers with inactive ALDH2 *2 allele were subjected to genotoxicity in a higher degree than those with ALDH2 *1/*1 genotype. Also, lower levels of urinary styrene metabolites (MA + PGA) were observed in styrene-exposed workers carrying ALDH2 *2 allele, suggesting slower metabolism of styrene. The polymorphisms of other enzymes showed less effect. These results suggested that styrene metabolism and styrene-induced genotoxicity could be particularly modified by ALDH2 polymorphisms. The important role of ALDH2 indicated that the accumulation of styrene glycoaldehyde, a possible genotoxic intermediate of styrene, could account for the genotoxicity observed, and should be taken as an increased risk of cancer.
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Choi YJ, Kim N, Jang W, Seo B, Oh S, Shin CM, Lee DH, Jung HC. Familial Clustering of Gastric Cancer: A Retrospective Study Based on the Number of First-Degree Relatives. Medicine (Baltimore) 2016; 95:e3606. [PMID: 27196462 PMCID: PMC4902404 DOI: 10.1097/md.0000000000003606] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
This comprehensive cross-sectional study aimed to identify factors contributing to familial aggregation of gastric cancer (GC). A total of 1058 GC patients and 1268 controls were analyzed separately according to the presence or absence of a first-degree relative of GC (GC-relative). Logistic regression analysis adjusted for age, gender, residence during childhood, smoking, alcohol intake, monthly income, spicy food ingestion, Helicobacter pylori status and host cytokine polymorphisms was performed. Cytotoxin-associated gene A (cagA) positivity was a distinctive risk factor for GC in the family history (FH)-positive group (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.42-4.00), while current/ex-smoker, moderate to strong spicy food ingestion, and non-B blood types were more closely associated with GC in the FH-negative group. Among the FH-positive group, alcohol consumption showed a synergistic carcinogenic effect in the at least 2 GC-relatives group compared to the 1 GC-relative group (1.71 vs. 9.58, P for interaction = 0.026), and this was dose-dependent. In the subjects with ≥2 GC-relatives, TGFB1-509T/T was a risk factor for GC (OR 23.74; 95% CI 1.37-410.91), as were rural residency in childhood, alcohol consumption, spicy food ingestion, and cagA positivity. These results suggest that subjects with FH may be a heterogeneous group in terms of gastric cancer susceptibility. Especially, subjects with ≥2 GC-relatives should undergo risk stratification including TGFB1-509T/T and alcohol consumption.
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Affiliation(s)
- Yoon Jin Choi
- From the Department of Internal Medicine (YJC, NK, CMS and DHL), Seoul National University Bundang Hospital, Seongnam; Department of Internal Medicine and Liver Research Institute (NK, SO, DHL and HCJ), Seoul National University College of Medicine; and Department of Statistics (WJ, BS), College of Science, Seoul National University, Seoul, South Korea
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Li R, Zhao Z, Sun M, Luo J, Xiao Y. ALDH2 gene polymorphism in different types of cancers and its clinical significance. Life Sci 2016; 147:59-66. [PMID: 26804999 DOI: 10.1016/j.lfs.2016.01.028] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 01/08/2016] [Accepted: 01/15/2016] [Indexed: 12/22/2022]
Abstract
Aldehyde dehydrogenase 2 (ALDH2), an important mitochondrial enzyme governing ethanol metabolism, displays polymorphism in human. Recent evidence suggested that genetic polymorphism in ALDH2 gene may be significantly correlated with the susceptibility to cancer, such as colorectal cancer, esophageal cancer, and liver cancer. To investigate the correlation between ALDH2 mutant gene and the risk of a certain cancer, many studies have been done by testing the ALDH2 genotype in patients with cancers. Here, we summarized 84 ALDH2 gene single nucleotide polymorphism (SNP) sites in human cancer, which focus primarily on the rs671 SNP site. As a novel biological marker, ALDH2 displays a very attractive prospect in the screening, diagnosis and evaluation of the prognosis of many diseases. Moreover, much attention has been attracted to the studies of the biological functions and potential value of ALDH2 in the human cancer treatment. This review will provide an overview about the clinical prospects of ALDH2 based on the available information.
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Affiliation(s)
- Rui Li
- Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Jilin University, Changchun, China; Department of Radiology, School of Public Health, Jilin University, Changchun, China
| | - Zihan Zhao
- School of Clinical Medicine, Jilin University, Changchun, China
| | - Mingyang Sun
- School of Clinical Medicine, Jilin University, Changchun, China
| | - Jiachi Luo
- College of Letters and Science, University of California, Berkeley, Berkeley, CA, USA
| | - Yechen Xiao
- Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Jilin University, Changchun, China.
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Alcohol intake and cardiovascular risk factors: A Mendelian randomisation study. Sci Rep 2015; 5:18422. [PMID: 26687910 PMCID: PMC4685310 DOI: 10.1038/srep18422] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Accepted: 10/26/2015] [Indexed: 11/08/2022] Open
Abstract
Mendelian randomisation studies from Asia suggest detrimental influences of alcohol on cardiovascular risk factors, but such associations are observed mainly in men. The absence of associations of genetic variants (e.g. rs671 in ALDH2) with such risk factors in women – who drank little in these populations – provides evidence that the observations are not due to genetic pleiotropy. Here, we present a Mendelian randomisation study in a South Korean population (3,365 men and 3,787 women) that 1) provides robust evidence that alcohol consumption adversely affects several cardiovascular disease risk factors, including blood pressure, waist to hip ratio, fasting blood glucose and triglyceride levels. Alcohol also increases HDL cholesterol and lowers LDL cholesterol. Our study also 2) replicates sex differences in associations which suggests pleiotropy does not underlie the associations, 3) provides further evidence that association is not due to pleiotropy by showing null effects in male non-drinkers, and 4) illustrates a way to measure population-level association where alcohol intake is stratified by sex. In conclusion, population-level instrumental variable estimation (utilizing interaction of rs671 in ALDH2 and sex as an instrument) strengthens causal inference regarding the largely adverse influence of alcohol intake on cardiovascular health in an Asian population.
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37
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Sun Y, Huang XJ, Chen L. New progress in study of risk factors for gastric cancer. Shijie Huaren Xiaohua Zazhi 2015; 23:4831-4837. [DOI: 10.11569/wcjd.v23.i30.4831] [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 the most common malignant tumors, and its etiology is not clear yet. Numerous studies show that the development of gastric cancer is a complex process related with many factors, such as demographic, lifestyle and diet, infectious, hereditary, socioeconomic, and mental factors. Early prevention can effectively reduce the incidence of gastric cancer. Here we make a review of the new progress in research of risk factors for gastric cancer.
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Abstract
Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval.
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Affiliation(s)
- Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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39
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Maejima R, Iijima K, Kaihovaara P, Hatta W, Koike T, Imatani A, Shimosegawa T, Salaspuro M. Effects of ALDH2 genotype, PPI treatment and L-cysteine on carcinogenic acetaldehyde in gastric juice and saliva after intragastric alcohol administration. PLoS One 2015; 10:e0120397. [PMID: 25831092 PMCID: PMC4382225 DOI: 10.1371/journal.pone.0120397] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 01/21/2015] [Indexed: 12/12/2022] Open
Abstract
Acetaldehyde (ACH) associated with alcoholic beverages is Group 1 carcinogen to humans (IARC/WHO). Aldehyde dehydrogenase (ALDH2), a major ACH eliminating enzyme, is genetically deficient in 30-50% of Eastern Asians. In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer. However, there is only a limited evidence for stomach cancer. In this study we demonstrated for the first time that ALDH2 deficiency results in markedly increased exposure of the gastric mucosa to acetaldehyde after intragastric administration of alcohol. Our finding provides concrete evidence for a causal relationship between acetaldehyde and gastric carcinogenesis. A plausible explanation is the gastric first pass metabolism of ethanol. The gastric mucosa expresses alcohol dehydrogenase (ADH) enzymes catalyzing the oxidation of ethanol to acetaldehyde, especially at the high ethanol concentrations prevailing in the stomach after the consumption of alcoholic beverages. The gastric mucosa also possesses the acetaldehyde-eliminating ALDH2 enzyme. Due to decreased mucosal ALDH2 activity, the elimination of ethanol-derived acetaldehyde is decreased, which results in its accumulation in the gastric juice. We also demonstrate that ALDH2 deficiency, proton pump inhibitor (PPI) treatment, and L-cysteine cause independent changes in gastric juice and salivary acetaldehyde levels, indicating that intragastric acetaldehyde is locally regulated by gastric mucosal ADH and ALDH2 enzymes, and by oral microbes colonizing an achlorhydric stomach. Markedly elevated acetaldehyde levels were also found at low intragastric ethanol concentrations corresponding to the ethanol levels of many foodstuffs, beverages, and dairy products produced by fermentation. A capsule that slowly releases L-cysteine effectively eliminated acetaldehyde from the gastric juice of PPI-treated ALDH2-active and ALDH2-deficient subjects. These results provide entirely novel perspectives for the prevention of gastric cancer, especially in established risk groups.
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Affiliation(s)
- Ryuhei Maejima
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Katsunori Iijima
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Pertti Kaihovaara
- Research Unit on Acetaldehyde and Cancer, University of Helsinki, Helsinki, Finland
| | - Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Akira Imatani
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tooru Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Mikko Salaspuro
- Research Unit on Acetaldehyde and Cancer, University of Helsinki, Helsinki, Finland
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Cai Q, Wu J, Cai Q, Chen EZ, Jiang ZY. Association between Glu504Lys polymorphism of ALDH2 gene and cancer risk: a meta-analysis. PLoS One 2015; 10:e0117173. [PMID: 25680115 PMCID: PMC4334541 DOI: 10.1371/journal.pone.0117173] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2014] [Accepted: 12/18/2014] [Indexed: 01/17/2023] Open
Abstract
Background The association of the aldehyde dehydrogenases-2 (ALDH2) Glu504Lys polymorphism (also named Glu487Lys, or rs671) and cancers has been investigated. This meta-analysis aims to comprehensively assess the influence of this polymorphism on the overall cancer risk. Methods Eligible publications were retrieved according to inclusion/exclusion criteria and the data were analyzed using the Review Manager software (V5.2). Results A meta-analysis based on 51 case-control studies consisting of 16774 cases and 32060 controls was performed to evaluate the association between the ALDH2 Glu504Lys polymorphism and cancer risk. The comparison of genotypes Lys+ (Lys/Lys and Lys/Glu) with Glu/Glu yielded a significant 20% increased cancer risk (OR = 1.20, 95%CI: 1.03–1.39, P = 0.02, I2 = 92%). Subgroup analysis by cancer type indicated a significantly increased UADT cancer risk (OR = 1.39, 95%CI: 1.11–1.73, P = 0.004, I2 = 94%) in individuals with the Lys+ genotypes. Subgroup analysis by country indicated that individuals from Japan with the Lys+ genotypes had a significant 38% increased cancer risk (OR = 1.38, 95%CI: 1.12–1.71, P = 0.003, I2 = 93%). Conclusions Our results indicated that the ALDH2 Glu504Lys polymorphism is a susceptible loci associated with overall cancers, especially esophageal cancer and among Japanese population.
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Affiliation(s)
- Qiang Cai
- Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Jian Wu
- Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Qu Cai
- Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Er-Zhen Chen
- Department of Emergency, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Zhao-Yan Jiang
- Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
- * E-mail:
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Hidaka A, Sasazuki S, Matsuo K, Ito H, Sawada N, Shimazu T, Yamaji T, Iwasaki M, Inoue M, Tsugane S. Genetic polymorphisms of ADH1B, ADH1C and ALDH2, alcohol consumption, and the risk of gastric cancer: the Japan Public Health Center-based prospective study. Carcinogenesis 2015; 36:223-231. [PMID: 25524923 DOI: 10.1093/carcin/bgu244] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The association between alcohol consumption, genetic polymorphisms of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) and gastric cancer risk is not completely understood. We investigated the association between ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms, alcohol consumption and the risk of gastric cancer among Japanese subjects in a population-based, nested, case-control study (1990-2004). Among 36 745 subjects who answered the baseline questionnaire and provided blood samples, 457 new gastric cancer cases matched to 457 controls were used in the analysis. The odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated using logistic regression models. No association was observed between alcohol consumption, ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms and gastric cancer risk. However, considering gene-environmental interaction, ADH1C G allele carriers who drink ≥150 g/week of ethanol had a 2.5-fold increased risk of gastric cancer (OR = 2.54, 95% CI = 1.05-6.17) relative to AA genotype carriers who drink 0 to <150 g/week (P for interaction = 0.02). ALDH2 A allele carriers who drink ≥150 g/week also had an increased risk (OR = 2.08, 95% CI = 1.05-4.12) relative to GG genotype carriers who drink 0 to < 150 g/week (P for interaction = 0.08). To find the relation between alcohol consumption and gastric cancer risk, it is important to consider both alcohol consumption level and ADH1C and ALDH2 polymorphisms.
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Affiliation(s)
- Akihisa Hidaka
- Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan
| | - Shizuka Sasazuki
- Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan,
| | - Keitaro Matsuo
- Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka 812-8582, Japan
| | - Hidemi Ito
- Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan, and
| | - Norie Sawada
- Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan
| | - Taichi Shimazu
- Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan
| | - Taiki Yamaji
- Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan
| | - Motoki Iwasaki
- Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan
| | - Manami Inoue
- Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan
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Song M, Lee HW, Kang D. Epidemiology and screening of gastric cancer in Korea. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2015. [DOI: 10.5124/jkma.2015.58.3.183] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Minkyo Song
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hwi-Won Lee
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Daehee Kang
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
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Eriksson CJP. Genetic–Epidemiological Evidence for the Role of Acetaldehyde in Cancers Related to Alcohol Drinking. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2014; 815:41-58. [DOI: 10.1007/978-3-319-09614-8_3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Kim J, Cho YA, Choi WJ, Jeong SH. Gene-diet interactions in gastric cancer risk: A systematic review. World J Gastroenterol 2014; 20:9600-9610. [PMID: 25071358 PMCID: PMC4110595 DOI: 10.3748/wjg.v20.i28.9600] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [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: 02/17/2014] [Accepted: 05/26/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To conduct a systematic review of the published epidemiological studies investigating the association of the interactions between gene variants and dietary intake with gastric cancer risk.
METHODS: A literature search was conducted in PubMed, EMBASE, and MEDLINE for articles published between January 2000 and July 2013, and 38 studies were identified. Previous studies included various dietary factors (e.g., fruits and vegetables, soybean products, salt, meat, and alcohol) and genetic variants that are involved in various metabolic pathways.
RESULTS: Studies suggest that individuals who carry high-risk genetic variants and demonstrate particular dietary habits may have an increased risk of gastric cancer compared with those who do not carry high-risk genetic variants. Distinctive dietary patterns and variations in the frequency of genetic variants may explain the higher incidence of gastric cancer in a particular region. However, most previous studies have limitations, such as a small sample size and a retrospective case-control design. In addition, past studies have been unable to elucidate the specific mechanism in gene-diet interaction associated with gastric carcinogenesis.
CONCLUSION: Additional large prospective epidemiological and experimental studies are required to identify the gene-diet metabolic pathways related to gastric cancer susceptibility.
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Wang HL, Zhou PY, Liu P, Zhang Y. ALDH2 and ADH1 genetic polymorphisms may contribute to the risk of gastric cancer: a meta-analysis. PLoS One 2014; 9:e88779. [PMID: 24633362 PMCID: PMC3954547 DOI: 10.1371/journal.pone.0088779] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2013] [Accepted: 01/13/2014] [Indexed: 01/11/2023] Open
Abstract
AIM We conducted a meta-analysis of case-control studies to determine whether ALDH2, ADH1 and ADH2 genetic polymorphisms contribute to the pathogenesis of gastric cancer. METHODS The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before November 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. We calculated crude odds ratios (ORs) with their 95% confidence intervals (95%CI) to evaluate their relationships under five genetic models. Seven case-control studies with a total of 2,563 gastric cancer patients and 4,192 healthy controls met the inclusion criteria. Nine common polymorphisms were evaluated, including rs671, rs16941667 and rs886205 in the ALDH2 gene, rs1230025, rs13123099, rs698 and rs1693482 in the ADH1 gene, and rs1229984 and rs17033 in the ADH2 gene. RESULTS The results of our meta-analysis suggested that ALDH2 genetic polymorphisms might be strongly correlated with an increased risk of gastric cancer (allele model: OR = 1.21, 95%CI: 1.11 ∼ 1.32, P<0.001; dominant model: OR = 1.23, 95%CI: 1.09 ∼ 1.39, P = 0.001; respectively), especially for rs671 polymorphism. Furthermore, we observed significant associations between ADH1 genetic polymorphisms and an increased risk of gastric cancer (allele model: OR = 1.21, 95%CI: 1.08 ∼ 1.36, P = 0.001; dominant model: OR = 10.52, 95%CI: 3.04 ∼ 36.41, P<0.001; respectively), especially for rs1230025 polymorphism. Nevertheless, no positive relationships were found between ADH2 genetic polymorphisms and gastric cancer risk (all P>0.05). CONCLUSION The current meta-analysis suggests that ALDH2 and ADH1 genetic polymorphisms may play crucial roles in the pathogenesis of gastric cancer. However, ADH2 genetic polymorphisms may not be important dominants of susceptibility to gastric cancer.
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Affiliation(s)
- He-Ling Wang
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, P. R. China
- * E-mail:
| | - Ping-Yi Zhou
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, P. R. China
| | - Peng Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, P. R. China
| | - Yu Zhang
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, P. R. China
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Song Q, Hu P, Wang J, Jia Y, Zhang G, Lv L, Liu Y, Cheng Y. Association between gastric cardia adenocarcinoma risk and alcohol flushing response, but not alcohol consumption. Med Oncol 2014; 31:858. [DOI: 10.1007/s12032-014-0858-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Accepted: 01/22/2014] [Indexed: 01/20/2023]
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Fan YF, Wu YM, Liu H, Yu Y, Jiang YY, Xue YZ, Liu ZL, Wei MX. TLR4 polymorphisms associated with developing gastric pre-cancer lesions in a Chinese Han population. Hum Immunol 2013; 75:176-81. [PMID: 24269697 DOI: 10.1016/j.humimm.2013.11.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2013] [Revised: 10/08/2013] [Accepted: 11/11/2013] [Indexed: 12/20/2022]
Abstract
Helicobacter pylori infection is a risk factor for gastric cancer. In addition, toll-like receptor 4 (TLR4) plays a fundamental role in pathogen recognition and activation of innate immunity. This study investigated the association of TLR4 polymorphisms with a risk of intestinal metaplasia (IM) and intraepithelial neoplasia (IN) in a Chinese Han population. This study analyzed TLR4 gene polymorphisms in 333 patients (IM, 193 cases; IN, 140 cases) and 312 atypia-free controls in a Chinese Han population using a Taqman allelic discrimination assay. The TLR4 single nucleotide polymorphisms +896A/G and +1196C/T were not associated with the risk of IM or IN. However, the single-locus analysis showed that the C allele of TLR4+2856T/C had significantly reduced risk of IM and IN [adjusted odds ratio (OR)=0.42; 95%CI=0.29-0.62 and OR=0.62; 95%CI=0.41-0.93, respectively] compared with the wild-type homozygote (TT). The frequencies of TLR4+2856T/C TC and T carrier were significantly lower in patients with Sydney's slight IM and low grade IN (P<0.01 and P=0.01, respectively), while the TC genotype showed a lower risk of moderate IM compared to healthy controls (P=0.045). In addition, the data revealed that H. pylori infection, heavy alcohol consumption and high salt uptake were associated with a higher susceptibility for developing this neoplasm. TLR4 rs10759932 TC and C carriers were associated with a lower risk in developing precancerous lesions in the stomach in a Chinese Han population.
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Affiliation(s)
- Yao-fu Fan
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Yan-min Wu
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; Department of Gastroenterology, The Third People's Hospital of Wuxi, Wuxi 214041, Jiangsu, China
| | - Hao Liu
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Yuan Yu
- Public Health Clinical Center Affiliated to Fudan University, Shanghai 201508, China
| | - Yang-yang Jiang
- Department of General Surgery, Wuxi Higher Health Vocational Technology School, Wuxi 214028, China
| | - Yu-zheng Xue
- Department of Gastroenterology, The Third People's Hospital of Wuxi, Wuxi 214041, Jiangsu, China
| | - Zong-liang Liu
- Department of Gastroenterology, The Third People's Hospital of Wuxi, Wuxi 214041, Jiangsu, China
| | - Mu-Xin Wei
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
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Shu L, Wang XQ, Wang SF, Wang S, Mu M, Zhao Y, Sheng J, Tao FB. Dietary patterns and stomach cancer: a meta-analysis. Nutr Cancer 2013; 65:1105-15. [PMID: 24168194 DOI: 10.1080/01635581.2013.828086] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Investigation of the relationship between dietary patterns and some chronic diseases becomes appealing in nutrition epidemiology. Many studies reported potential associations between different dietary patterns and the risk of stomach cancer, however, a consistent perspective hasn't been established to date. Herein, we carried this meta-analysis to identify the associations between different dietary patterns and the risk of stomach cancer. A total of 23 studies met the inclusion criteria and were included in this meta-analysis. A decreased risk of stomach cancer was shown for the highest compared with the lowest category of a "healthy" dietary pattern [odds ratio (OR) = 0.69; confidence interval (CI): 0.53, 0.89; P = 0.005). There were evidence of the increased risk of stomach cancer in the highest compared with the lowest categories of Western-style pattern (OR = 1.59; CI: 1.25, 2.04; P = 0.0002) and alcohol-drinking pattern (OR = 1.37; CI: 1.11, 1.70; P = 0.004). The results of this meta-analysis indicate that healthy dietary pattern may decrease the risk of stomach cancer, whereas Western-style and alcohol-drinking dietary patterns may increase the risk of stomach cancer.
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Affiliation(s)
- Long Shu
- a School of Public Health, Anhui Medical University , Hefei , 230032 , Anhui , China
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Time characteristics of the effect of alcohol cessation on the risk of stomach cancer--a meta-analysis. BMC Public Health 2013; 13:600. [PMID: 23786883 PMCID: PMC3695890 DOI: 10.1186/1471-2458-13-600] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2012] [Accepted: 06/12/2013] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND In the Bagnardi et al. (2001) meta-analysis, it was found that alcohol consumption increases the risk of stomach cancer (OR = 1.32 for heavy drinkers). However, it is unknown if drinking cessation reverses this alcohol-elevated risk. METHODS A systematic literature review was performed to provide the information for a meta-analysis where the dose-risk trend was estimated for years since drinking cessation and the risk of stomach cancer. A random effect generalised least squares model for trend estimation was used, employing study characteristics to control for heterogeneity. RESULTS Nineteen observational studies were identified in the literature review, of which five studies quantified duration of cessation and risk of stomach cancer, giving a total of 1947 cancer cases. No significant effect of drinking cessation on the risk of stomach cancer could be found (OR = 0.99 CI: 0.97-1.02). CONCLUSIONS This result should be interpreted with caution due to the limited number of studies in this area. Recent findings suggest a link between heavy drinking and stomach cancer, especially gastric noncardia, but not for moderate drinking. Since all but one of the included studies in this meta-analysis failed to control for consumption level, the current study could not test if the risk decline following drinking cessation differs between moderate and high consumers.
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Matsuo K, Oze I, Hosono S, Ito H, Watanabe M, Ishioka K, Ito S, Tajika M, Yatabe Y, Niwa Y, Yamao K, Nakamura S, Tajima K, Tanaka H. The aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism interacts with alcohol drinking in the risk of stomach cancer. Carcinogenesis 2013; 34:1510-5. [PMID: 23455379 DOI: 10.1093/carcin/bgt080] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The impact of alcohol on the risk of stomach cancer is controversial. Although aldehyde dehydrogenase 2 (ALDH2) Glu504Lys (rs671) polymorphism has a strong effect on acetaldehyde metabolism, little is known about its impact on stomach cancer risk when combined with alcohol drinking. This case-control study included a total of 697 incident stomach cancer case subjects and 1372 non-cancer control subjects who visited Aichi Cancer Center between 2001 and 2005. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2 genotypes and alcohol consumption using logistic regression models after adjustment for potential confounders, including Helicobacter pylori infection. The ALDH2 504Lys allele was associated with the risk of stomach cancer, with adjusted ORs of 1.40 (95% CI, 1.11-1.76) for Glu/Lys and 1.73 (1.12-2.68) for Lys/Lys compared with Glu/Glu. Heavy drinking was associated with risk (OR 1.72, 1.17-2.52) after adjustment for ALDH2 genotype and other confounders. Moreover, ORs for heavy drinking were 1.28 (0.77-2.12) for those with ALDH2 Glu/Glu and 3.93 (1.99-5.79) for those with the ALDH2 Lys allele relative to non-drinkers with the Glu/Glu genotype (P for interaction = 0.0054). In conclusion, ALDH2 and alcohol drinking showed interaction for risk factors of stomach cancer, indicating that acetaldehyde plays a role in stomach carcinogenesis.
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Affiliation(s)
- Keitaro Matsuo
- Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
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