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Paiva Prudente T, Mezaiko E, Nunes Pereira Oliva H, Yamamoto-Silva FP, Santos de Freitas Silva B, Oliveira Oliva I, Risch H. Associations between colonization with Helicobacter pylori and risk of gastrointestinal tract cancers: An umbrella review of meta-analyses. Eur J Clin Invest 2025:e14394. [PMID: 39878420 DOI: 10.1111/eci.14394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 01/15/2025] [Indexed: 01/31/2025]
Abstract
BACKGROUND Several studies have investigated the association between Helicobacter pylori colonization and gastrointestinal malignancies. However, inconsistent results have been found, leaving no clear consensus. MATERIALS AND METHODS Umbrella review of meta-analyses of observational studies aiming to understand the association between Helicobacter pylori colonization and gastrointestinal cancers in humans. MEDLINE, the Cochrane Library of Systematic Reviews, EMBASE, Scopus and Google Scholar were searched from their inception to January 2025. Quality assessment was performed with the AMSTAR 2 tool. The study was registered on PROSPERO (CRD42024523832). RESULTS Of 1320 records, 38 meta-analyses were included, investigating biliary tract, colorectal, oesophageal, gastric, liver and pancreatic cancers. After dealing with primary study overlap and updating meta-analyses with over 160 studies, Helicobacter pylori was positively associated with biliary tract [OR 2.67 (1.57-4.52)], colorectal [OR 1.40 (1.23-1.60)], gastric [OR 2.10 (1.34-3.31)], liver [OR 5.13 (3.14-8.38)] and pancreatic [OR 1.24 (1.04-1.48)] cancers, while oesophageal adenocarcinoma (EAC) was inversely associated with it [OR .58 (.46-.72)]. The cytotoxic-associated gene A (CagA) protein was positively associated with biliary [OR 2.19 (1.07-4.50)], colorectal [OR 2.04 (1.47-2.82)], oesophageal squamous cell carcinoma [OR 1.56 (1.30-1.89)] and gastric cancers [OR 2.53 (1.94-3.30)], and inversely associated with EAC [OR .60 (.44-.81)] and pancreatic [OR .85 (.75-.97)] cancers. Our results sprout from mostly critically low-quality meta-analyses and moderate to high quality primary studies. CONCLUSION Exposure to Helicobacter pylori colonization and its proteins is associated with not only gastric cancer, but also other GI tract cancers. Directionally different results may be seen when specific virulence factors/organ sites are investigated.
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Affiliation(s)
| | - Eleazar Mezaiko
- Department of Oral Medicine, Universidade Federal de Goiás, Goiânia, Brazil
| | | | | | | | | | - Harvey Risch
- Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA
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Hao Y, Wang M, Jiang X, Zheng Y, Ran Q, Xu X, Zou B, Wang J, Liu N, Qin B. Non-acid reflux and esophageal dysmotility is associated with early esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 2023; 149:8327-8334. [PMID: 37074455 DOI: 10.1007/s00432-023-04772-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 04/08/2023] [Indexed: 04/20/2023]
Abstract
BACKGROUND Studies have demonstrated that non-acid reflux (NAR) is associated with esophageal squamous cell carcinoma (ESCC). Esophageal dysmotility is associated with NAR but few studies have focused on the esophageal motility of ESCC patients. We explored the relationship between ESCC, NAR and esophageal dysmotility with the aid of multichannel intraluminal impedance and pH (MII-pH) and high-resolution manometry (HRM). METHODS From Jan 2021 to Oct 2022, 20 patients with superficial ESCC were enrolled as the ESCC group, while 20 age and gender matched individuals without gastroesophageal reflux disease (GERD) symptoms and 20 age and gender matched patients with GERD symptoms were recruited as the control groups. Patients received 24 h MII-pH and HRM procedure before endoscopic submucosal dissection (ESD), and the data were then collected to identify the type of reflux and esophageal dysmotility. RESULTS Prevalence of esophageal dysmotility was significantly different among the three groups, 75.0% in the ESCC group, 35.0% in the non-GERD group and 70.0% in the GERD group (P = 0.029). NAR episodes at 15 cm above the lower esophageal sphincter (LES) in the ESCC group were significantly higher than that in the non-GERD group (6.5 (3.5-9.3) vs 1.0 (0.8-4.0), P = 0.001) and were similar with that in the GERD group (6.5 (3.5-9.3) vs 5.5 (3.0-10.5), P > 0.05). NAR episodes at 5 cm above LES was significantly higher in the ESCC group than that in the non-GERD group (38.0 (27.0-60.0) vs 18.0 (11.8-25.8), P = 0.001) and was significantly higher than that in the GERD group (38.0 (27.0-60.0) vs 20.0 (9.8-30.5)), P = 0.010). Prevalence of pathologic non-acid reflux was significantly different among the three groups, 30.0% in the ESCC group, 0.0% in the non-GERD group and 10.0% in the GERD group (P < 0.001). CONCLUSION Our study found NAR and esophageal dysfunction frequently occur in ESCC patients. NAR and esophageal dysmotility may be associated with ESCC. CLINICAL TRIAL REGISTRATION NUMBER ChiCTR2200061456.
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Affiliation(s)
- Yujie Hao
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Mo Wang
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China
| | - Xiaosa Jiang
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Yueqin Zheng
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Qiuju Ran
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Xiaoyu Xu
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Baicang Zou
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Jinhai Wang
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China.
| | - Na Liu
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China.
| | - Bin Qin
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China.
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Pan D, Sun GJ, Su M, Wang X, Yan QY, Song G, Wang YY, Xu DF, Wang NN, Wang SK. Inverse relations between Helicobacter pylori infection and risk of esophageal precancerous lesions in drinkers and peanut consumption. World J Gastrointest Oncol 2022; 14:1689-1698. [PMID: 36187387 PMCID: PMC9516658 DOI: 10.4251/wjgo.v14.i9.1689] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 06/16/2022] [Accepted: 08/05/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a Gram-negative bacterium found in the upper digestive tract. Although H. pylori infection is an identified risk factor for gastric cancer, its role in esophageal squamous cell carcinoma (ESCC) remains a topic of much debate. AIM To evaluate the association between H. pylori infection and the risk of precancerous lesions of ESCC, and further explore the association between dietary factors and the risk of H. pylori infection. METHODS Two hundred patients with esophageal precancerous lesions (EPL) aged 63.01 ± 6.08 years and 200 healthy controls aged 62.85 ± 6.03 years were included in this case-control study. Epidemiological data and qualitative food frequency data were investigated. Enzyme-linked immunosorbent assay measuring serum immunoglobulin G antibodies was used to determine H. pylori seropositivity. An unconditional logistic regression model was used to assess the association between H. pylori infection and EPL risk dichotomized by gender, age, and the use of tobacco and alcohol, as well as the association between dietary factors and the risk of H. pylori infection. RESULTS A total of 47 (23.5%) EPL cases and 58 (29.0%) healthy controls had positive H. pylori infection. An inverse relation between H. pylori infection and the risk of EPL was found in the group of drinkers after adjustment for covariates [odds ratio (OR) = 0.32, 95% confidence interval (95%CI): 0.11-0.95]. Additionally, peanut intake was significantly associated with a decreased risk of H. pylori infection (OR = 0.39, 95%CI: 0.20-0.74). CONCLUSION Our study suggested that H. pylori infection may decrease the risk of EPL for drinkers in a rural adult Chinese population, and the consumption of peanut may reduce the risk of H. pylori infection. These findings should be framed as preliminary evidence, and further studies are required to address whether the mechanisms are related to the localization of lesions and alcohol consumption.
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Affiliation(s)
- Da Pan
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene,School of Public Health, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Gui-Ju Sun
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene,School of Public Health, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ming Su
- Department of Chronic Disease, Huai’an District Center for Disease Control and Prevention, Huai’an 223200, Jiangsu Province, China
| | - Xin Wang
- Department of Chronic Disease, Huai’an District Center for Disease Control and Prevention, Huai’an 223200, Jiangsu Province, China
| | - Qing-Yang Yan
- Department of Chronic Disease, Huai’an District Center for Disease Control and Prevention, Huai’an 223200, Jiangsu Province, China
| | - Guang Song
- Department of Chronic Disease, Huai’an District Center for Disease Control and Prevention, Huai’an 223200, Jiangsu Province, China
| | - Yuan-Yuan Wang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene,School of Public Health, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Deng-Feng Xu
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene,School of Public Health, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Nian-Nian Wang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene,School of Public Health, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Shao-Kang Wang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene,School of Public Health, Southeast University, Nanjing 210009, Jiangsu Province, China
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Yang ZX, Yan LB, Xie P, Hu P, Zhao W, Lu Y, Xing X, Liu X. Association of Serum Pepsinogens With Esophageal Squamous Cell Carcinoma Risk: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:928672. [PMID: 35847871 PMCID: PMC9280489 DOI: 10.3389/fonc.2022.928672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 05/27/2022] [Indexed: 12/24/2022] Open
Abstract
Background Serum pepsinogens are serological biomarkers of gastric atrophy, and the latter is a risk factor for esophageal squamous cell carcinoma (ESCC). However, the association of serum pepsinogens with ESCC risk remains unclear. This systematic review and meta-analysis aimed to assess the relationship between serum pepsinogen I (PGI) and pepsinogen I: pepsinogen II ratio (PGR) and ESCC risk. Methods PubMed, Embase, and Web of Science were searched for articles on the effect of serum PGI and PGR on ESCC risk, published up to the end of February 2022. Meta-analysis with a random-effect model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results Five case–control studies and three prospective studies were included. In comparison with the high categories, the low categories of serum PGI (OR: 1.92, 95% CI: 1.45–2.56) and PGR (OR: 1.70, 95% CI: 1.01–2.85) were associated with an increased risk of ESCC, although a substantial heterogeneity was observed in serum PGR (I2 = 60.2%, P = 0.028) rather than in serum PGI (I2 = 46.4%, P = 0.070). In stratified analysis by study quality, the significant risk effect on ESCC was remained for PGI (OR: 2.05, 95% CI: 1.48–2.84) and PGR (OR: 2.07, 95% CI: 1.17–3.75) when only the studies with high quality were pooled. Conclusions Based on the available studies, although limited in number, this systematic review along with meta-analysis suggests that low serum PGI and low PGR may be related to an increased risk of ESCC. This present study provides evidence for using serum pepsinogen biomarkers in predicting ESCC. More delicate well-designed cohort studies with high study quality are needed, and dose–response analysis should be performed.
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Affiliation(s)
- Zhen-Xiao Yang
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China
| | - Lu-Bin Yan
- Department of Pediatric Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Peng Xie
- Department of General Surgery, Xi’an Aerospace General Hospital, Xi’an, China
| | - Peng Hu
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Wenjing Zhao
- School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China
- *Correspondence: Xudong Liu, ; Wenjing Zhao, ; Yi Lu,
| | - Yi Lu
- Health Effects Institute, Boston, MA, United States
- *Correspondence: Xudong Liu, ; Wenjing Zhao, ; Yi Lu,
| | - Xiangbing Xing
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xudong Liu
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China
- *Correspondence: Xudong Liu, ; Wenjing Zhao, ; Yi Lu,
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Systematic Review with Meta-analysis: Association of Helicobacter pylori Infection with Esophageal Cancer. Gastroenterol Res Pract 2019; 2019:1953497. [PMID: 31871444 PMCID: PMC6913313 DOI: 10.1155/2019/1953497] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 10/21/2019] [Accepted: 11/08/2019] [Indexed: 12/13/2022] Open
Abstract
Background Helicobacter pylori is an important carcinogenic factor in gastric cancer. Studies have shown that Helicobacter pylori infection is inversely associated with certain diseases such as esophageal cancer and whose infection appears to have a “protective effect.” At present, the relationship between Helicobacter pylori infection and esophageal cancer remains controversial. This study was designed to investigate the relationship between Helicobacter pylori infection and the risk of esophageal cancer in different regions and ethnicities. Methods Systematic search of the articles on the relationship between Helicobacter pylori infection and esophageal cancer from the database with the duration time up to December 2018. This systematic review was performed under the MOOSE guidelines. Results This meta-analysis included 35 studies with 345,886 patients enrolled. There was no significant correlation between Helicobacter pylori infection and esophageal squamous cell carcinoma in the general population (OR: 0.84; 95% CI: 0.64-1.09/OR: 0.74; 95% CI: 0.54-0.97). However, a significant correlation was found in the Middle East (OR: 0.34; 95% CI: 0.22-0.52/95% CI: 0.26-0.44). There was no significant difference in the prevalence of Helicobacter pylori between the case group and the control group in esophageal adenocarcinoma (8.87% vs. 9.67%). The pooled OR was 0.55 (95% CI: 0.43-0.70) or 0.23 (95% CI: 0.15-0.36). When grouped by match or not, the pooled OR of the nonmatching group and the matching group was 0.48/0.21 (95% CI: 0.36-0.65/95% CI: 0.13-0.36) and 0.73/0.71 (95% CI: 0.57-0.92/95% CI: 0.60-0.84), respectively. Conclusion In the general populations, no significant association was found between Helicobacter pylori infection and the risk of esophageal squamous cell carcinoma. However, lower risk was found in the Middle East. Helicobacter pylori infection may reduce the risk of esophageal adenocarcinoma, but such “protection effect” may be overestimated.
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Liu XB, Gao ZY, Zhang QH, Jin S, Gao B, Yang GL, Li SB. Serum pepsinogen assay is not recommended for the diagnosis of esophageal squamous cell carcinoma: a systematic review and meta-analysis. Cancer Manag Res 2019; 11:5643-5654. [PMID: 31303787 PMCID: PMC6603290 DOI: 10.2147/cmar.s196760] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Accepted: 05/16/2019] [Indexed: 12/24/2022] Open
Abstract
Background: Serum pepsinogen I (PGI) concentration and PGI/PGII ratio (PGR) are often used as serological markers for gastric fundus atrophy (AGA) and gastric carcinoma. However, their diagnostic value in esophageal carcinoma (EC) is inaccurate. Methods: This study evaluated the diagnostic value of PGI and PGR in EC by searching the PubMed, Web of Science, Embase, Cochrane Library and Cochrane Central Register of Controlled Trials databases for literature on the diagnosis of EC with PGI and PGR from January 1, 2000 to October 2, 2018. The included literature were systematically evaluated using QUSDAS-2 software. Meta-analysis was conducted using STATA 15.0 software. The summary receiver operating characteristic curve (SROC) accuracy was plotted, the area under the curve was calculated. Results: A total of 84 papers were selected, and after screening, nine papers on esophageal squamous cell carcinoma (ESCC) were finally included. Results showed low an ESCC-specific diagnostic sensitivity (0.27), high specificity (0.85), and 0.63 AUC of SROC when PGI≤70 ng/mL. When PGR≤3, the ESCC-specific diagnostic sensitivity was low (0.29), the specificity was high (0.83), and the AUC of SROC was 0.63. Conclusion: According to the current research results, PGI≤70 ng/mL or PGR≤3 diagnostic ESCC sensitivity is low, and specificity is high. These findings indicate that neither PGI≤70 ng/mL nor PGR≤3 can be used as an ESCC-screening index.
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Affiliation(s)
- Xiao-Bo Liu
- Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, People's Republic of China
| | - Zi-Ye Gao
- Department of Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, People's Republic of China
| | - Qing-Hui Zhang
- Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, People's Republic of China
| | - Shu Jin
- Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, People's Republic of China
| | - Bo Gao
- Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, People's Republic of China
| | - Gong-Li Yang
- Department of Gastroenterology, Shenzhen University General Hospital, Shenzhen, Guangdong 518000, People's Republic of China
| | - Sheng-Bao Li
- Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, People's Republic of China
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Okada M, Ishimura N, Mikami H, Okimoto E, Oshima N, Miyaoka Y, Fujishiro H, Ishihara S, Kinoshita Y. Circumferential distribution and clinical characteristics of esophageal cancer in lower esophagus: differences related to histological subtype. Esophagus 2019; 16:98-106. [PMID: 30145681 DOI: 10.1007/s10388-018-0639-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 08/21/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Esophageal adenocarcinoma (EAC) is frequently found on the right-anterior wall of the distal esophagus in short-segment Barrett's esophagus (SSBE) patients. However, the endoscopic characteristics of EAC in cases with long-segment BE (LSBE) and squamous cell carcinoma (ESCC) in the lower esophagus remain to be fully evaluated. Here, we determined the circumferential distribution and clinical characteristics of esophageal cancer occurring in the lower esophagus based on histological subtype. METHODS We retrospectively reviewed the medical records of 150 patients with esophageal cancer (ESCC, n = 100; EAC, n = 50) diagnosed at our hospital or a related facility between January 2002 and June 2017, including information regarding endoscopic findings, etiology, and clinical parameters. RESULTS Of the 100 patients with ESCC, 28 lesions were located in the lower esophagus, though characteristic circumferential distribution was not seen regardless of location. Those showed a greater frequency of smoking and drinking habit and gastric mucosal atrophy as compared to patients with EAC. Consistent with the previous reports, EAC in SSBE (n = 41) was frequently located on the right-anterior wall. Likewise, EAC at the esophagogastric junction (EGJ) in LSBE was frequently located on the right-anterior wall, while EAC distant from the EGJ showed no characteristic circumferential distribution. CONCLUSION Our results showed no circumferential predilection for ESCC in the lower esophagus, suggesting that development of this type of lesion may be less affected by gastroesophageal reflux. In addition, EAC at the EGJ was frequently found on the right-anterior wall irrespective of BE length.
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Affiliation(s)
- Mayumi Okada
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Norihisa Ishimura
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.
| | - Hironobu Mikami
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Eiko Okimoto
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Naoki Oshima
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Youichi Miyaoka
- Division of Endoscopy, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Hirofumi Fujishiro
- Division of Gastroenterology, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Shunji Ishihara
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Yoshikazu Kinoshita
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
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Key role of local acetaldehyde in upper GI tract carcinogenesis. Best Pract Res Clin Gastroenterol 2017; 31:491-499. [PMID: 29195668 DOI: 10.1016/j.bpg.2017.09.016] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Revised: 09/11/2017] [Accepted: 09/22/2017] [Indexed: 01/31/2023]
Abstract
Ethanol is neither genotoxic nor mutagenic. Its first metabolite acetaldehyde, however, is a powerful local carcinogen. Point mutation in ALDH2 gene proves the causal relationship between acetaldehyde and upper digestive tract cancer in humans. Salivary acetaldehyde concentration and exposure time are the two major and quantifiable factors regulating the degree of local acetaldehyde exposure in the ideal target organ, oropharynx. Instant microbial acetaldehyde formation from alcohol represents >70% of total ethanol associated acetaldehyde exposure in the mouth. In the oropharynx and achlorhydric stomach acetaldehyde is not metabolized to safe products, instead in the presence of alcohol it accumulates in saliva and gastric juice in mutagenic concentrations. A common denominator in alcohol, tobacco and food associated upper digestive tract carcinogenesis is acetaldehyde. Epidemiological studies on upper GI tract cancer are biased, since they miss information on acetaldehyde exposure derived from alcohol and acetaldehyde present in 'non-alcoholic' beverages and food.
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Iijima K, Koike T, Abe Y, Ohara S, Nakaya N, Shimosegawa T. Time series analysis of gastric acid secretion over a 20-year period in normal Japanese men. J Gastroenterol 2015; 50:853-61. [PMID: 25528645 DOI: 10.1007/s00535-014-1031-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Accepted: 12/07/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND The gastric acid secretion level is an important determinant for the manifestation of the gastroesophageal reflux disease spectrum, finally leading to the development of esophageal adenocarcinoma (EAC). Although the incidence of EAC has remained low in Asia, understanding the recent trend in gastric acid secretion should be helpful in estimating future incidences of EAC in that area. We investigated the latest chronological change (1995-2014) in gastric acid secretion in normal Japanese patients. METHODS A total of 307 asymptomatic Japanese men who attended the clinic for annual endoscopic checkups from 1995 to 2014 were enrolled in this analysis. Gastrin-stimulated gastric acid secretion was estimated with the endoscopic gastrin test. The association between gastric acid secretion and chronological period was assessed with a multivariate linear regression analysis. RESULTS Overall gastric acid secretion gradually increased over the 20-year period in the entire cohort in the unadjusted analysis (p < 0.05). However, the apparent increase was largely related to the relative decreasing rate of H. pylori infection, which profoundly inhibited gastric acid secretion. Gastric acid secretion did not change over the 20-year period in H. pylori-negative subjects, and it showed only a mild increase during this period in H. pylori-positive subjects. CONCLUSIONS Considering that gastric acid secretion remained unchanged in H. pylori-negative Japanese men over a 20-year period at a level much lower than that in Occidental subjects, upper gastrointestinal disease profiles in the Japanese population will differ from those in Western countries in the post-H. pylori era.
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Affiliation(s)
- Katsunori Iijima
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan,
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24-Hour Measurement of Gastric pH in Rural South Africa. Gastroenterol Res Pract 2015; 2015:658106. [PMID: 25861260 PMCID: PMC4377471 DOI: 10.1155/2015/658106] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Revised: 02/20/2015] [Accepted: 02/28/2015] [Indexed: 11/25/2022] Open
Abstract
Background. Previous studies have established norms of 24-hour gastric pH profiles for western countries. This study was designed to establish the pattern for a rural African population with a high incidence of oesophageal cancer. Methods. After lower oesophageal manometry a probe was placed 10 cm distal to the lower oesophageal sphincter. We carried out 24-hour ambulatory monitoring of gastric pH on 59 healthy subjects. This was satisfactorily completed on 26 female and 18 male (age 21–64, median 35) subjects in the Transkei region of South Africa. Results. The mean 24 hour gastric pH was 2.84 and the mean night-time pH was 3.7. 40 volunteers recorded a night-time pH reaching over 4. 33 volunteers recorded a night-time pH over 7. Night-time alkalinisation was present for 136.4 minutes (25th centile 22.8, 75th centile 208.1) at pH4 or over, and 79.3 (2.5, 122.7) minutes at pH7 or over. Episodes of rapid alkaline rise were 17 (10, 47). 21.1% of these occurred while supine. 35 of 36 tested subjects were positive for H. pylori IgG. Conclusion. Gastric alkalinisation is common in Transkei, at a higher pH than that reported in other studies, and is sustained longer. Nighttime alkalinisation is frequent. This suggests a high level of duodenogastric reflux.
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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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Mandal U, Ali KM, Chatterjee K, De D, Biswas A, Ghosh D. Management of experimental hypochlorhydria with iron deficiency by the composite extract of Fumaria vaillantii L. and Benincasa hispida T. in rat. J Nat Sci Biol Med 2014; 5:397-403. [PMID: 25097423 PMCID: PMC4121923 DOI: 10.4103/0976-9668.136202] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
The aim of the present study was to search the effective ratio of whole plant of Fumaria vaillantii Loisel (Fumaria vaillantii L.) and fruit of Benincasa hispida Thunb. (Benincasa hispida T.) in composite form, namely “FVBH” for the management of hypochlorhydria along with iron deficiency in male albino rats. Hypochlorhydria refers to suppression of hydrochloric acid secretion by the stomach. Hypochlorhydria was induced by ranitidine in this study. We used four composite extracts of the mentioned plant and fruit with different ratios (1:1, 1:2, 2:1, and 3:2) for searching the most effective composite extract for the correction of hypochlorhydria. Gastric acidity is an important factor for iron absorption. Thus, hypochlorhydria causes iron deficiency in rat and it was prevented significantly by the extract treatment at the ratio of 1:1 of the said plant and fruit. The correction of iron deficiency by the composite extract was compared with iron supplementation to hypochlorhydric rat. It was found that preadministration followed by coadministration of FVBH-1 (1:1) able to prevent the ranitidine-induced hypochlorhydria and iron deficiency. The composite extract, FVBH-1 (1:1) significantly (P<0.05) increased the pepsin concentration, chloride level in gastric juice, iron levels in serum and liver along with blood hemoglobin level than other ratios used here. Hence, it can be concluded that FVBH-1 (1:1) is an effective herbal formulation for the management of hypochlorhydria and related iron deficiency.
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Affiliation(s)
- Upanandan Mandal
- Andrology, Endocrinology and Molecular Medicine Laboratory, Department of Bio-Medical Laboratory Science and Management (UGC Innovative Department), Vidyasagar University, Midnapore, West Bengal, India
| | - Kazi Monjur Ali
- Andrology, Endocrinology and Molecular Medicine Laboratory, Department of Bio-Medical Laboratory Science and Management (UGC Innovative Department), Vidyasagar University, Midnapore, West Bengal, India
| | - Kausik Chatterjee
- Andrology, Endocrinology and Molecular Medicine Laboratory, Department of Bio-Medical Laboratory Science and Management (UGC Innovative Department), Vidyasagar University, Midnapore, West Bengal, India
| | - Debasis De
- Andrology, Endocrinology and Molecular Medicine Laboratory, Department of Bio-Medical Laboratory Science and Management (UGC Innovative Department), Vidyasagar University, Midnapore, West Bengal, India
| | - Anjan Biswas
- Department of Physiology, Presidency University, Kolkata, West Bengal, India
| | - Debidas Ghosh
- Andrology, Endocrinology and Molecular Medicine Laboratory, Department of Bio-Medical Laboratory Science and Management (UGC Innovative Department), Vidyasagar University, Midnapore, West Bengal, India
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Huang L, Xu AM, Li TJ, Han WX, Xu J. Should peri-gastrectomy gastric acidity be our focus among gastric cancer patients? World J Gastroenterol 2014; 20:6981-6988. [PMID: 24944492 PMCID: PMC4051941 DOI: 10.3748/wjg.v20.i22.6981] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 03/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the necessity and correctness of acid suppression pre- and post-gastrectomy among gastric carcinoma (GC) patients.
METHODS: From June 2011 to April 2013, 99 patients who were diagnosed with GC or adenocarcinoma of the gastroesophageal junction (type II or III) and needed surgical management were enrolled. They all underwent gastrectomy by the same operators [35 undergoing total gastrectomy (TG) plus Roux-en-Y reconstruction, 34 distal gastrectomy (DG) plus Billroth I reconstruction, and 30 proximal gastrectomy (PG) plus gastroesophagostomy]. We collected and analyzed their gastrointestinal juice and tissues from the pre-operational day to the 5th day post-operation, and 6 mo post-surgery. Gastric pH was detected with a precise acidity meter. Gastric juice contents including potassium, sodium and bicarbonate ions, urea nitrogen, direct and indirect bilirubin, and bile acid were detected using Automatic Biochemical Analyzer. Data regarding tumor size, histological type, tumor penetration and tumor-node-metastasis (TNM) stage were obtained from the pathological records. Reflux symptoms pre- and 6 mo post-gastrectomy were evaluated by reflux disease questionnaire (RDQ) and gastroesophageal reflux disease questionnaire (GERD-Q). SPSS 16.0 was applied to analyze the data.
RESULTS: Before surgery, gastric pH was higher than the threshold of hypoacidity (4.25 ± 1.45 vs 3.5, P = 0.000), and significantly affected by age, tumor size and differentiation grade, and potassium and bicarbonate ions; advanced malignancies were accompanied with higher pH compared with early ones (4.49 ± 1.31 vs 3.66 ± 1.61, P = 0.008). After operation, gastric pH in all groups was of weak-acidity and significantly higher than that pre-gastrectomy; on days 3-5, comparisons of gastric pH were similar between the 3 groups. Six months later, gastric pH was comparable to that on days 3-5; older patients were accompanied with higher total bilirubin level, indicating more serious reflux (r = 0.238, P = 0.018); the TG and PG groups had higher RDQ (TG vs DG: 15.80 ± 5.06 vs 12.26 ± 2.14, P = 0.000; PG vs DG: 15.37 ± 3.49 vs 12.26 ± 2.14, P = 0.000) and GERD-Q scores (TG vs DG: 10.54 ± 3.16 vs 9.15 ± 2.27, P = 0.039; PG vs DG: 11.00 ± 2.07 vs 9.15 ± 2.27, P = 0.001) compared with the DG group; all gastric juice contents except potassium ion significantly rose; reflux symptom was significantly associated with patient’s body mass index, direct and indirect bilirubin, and total bile acid, while pH played no role.
CONCLUSION: Acidity is not an important factor causing unfitness among GC patients. There is no need to further alkalify gastrointestinal juice both pre- and post-gastrectomy.
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Lin Y, Totsuka Y, He Y, Kikuchi S, Qiao Y, Ueda J, Wei W, Inoue M, Tanaka H. Epidemiology of esophageal cancer in Japan and China. J Epidemiol 2013; 23:233-42. [PMID: 23629646 PMCID: PMC3709543 DOI: 10.2188/jea.je20120162] [Citation(s) in RCA: 427] [Impact Index Per Article: 35.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
In preparation for a collaborative multidisciplinary study of the pathogenesis of esophageal cancer, the authors reviewed the published literature to identify similarities and differences between Japan and China in esophageal cancer epidemiology. Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type, while the incidence of esophageal adenocarcinoma remains extremely low in both countries. Numerous epidemiologic studies in both countries show that alcohol consumption and cigarette smoking are contributing risk factors for ESCC. There are differences, however, in many aspects of esophageal cancer between Japan and China, including cancer burden, patterns of incidence and mortality, sex ratio of mortality, risk factor profiles, and genetic variants. Overall incidence and mortality rates are higher in China than in Japan, and variation in mortality and incidence patterns is greater in China than in Japan. During the study period (1987–2000), the decline in age-adjusted mortality rates was more apparent in China than in Japan. Risk factor profiles differed between high- and low-incidence areas within China, but not in Japan. The association of smoking and drinking with ESCC risk appears to be weaker in China than in Japan. Genome-wide association studies in China showed that variants in several chromosome regions conferred increased risk, but only genetic variants in alcohol-metabolizing genes were significantly associated with ESCC risk in Japan. A well-designed multidisciplinary epidemiologic study is needed to examine the role of diet and eating habits in ESCC risk.
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Affiliation(s)
- Yingsong Lin
- Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
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15
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Almodova EDC, Oliveira WKD, Machado LFA, Grejo JR, Cunha TRD, Colaiacovo W, Ortolan EVP. Atrophic gastritis: Risk factor for esophageal squamous cell carcinoma in a Latin-American population. World J Gastroenterol 2013; 19:2060-2064. [PMID: 23599625 PMCID: PMC3623983 DOI: 10.3748/wjg.v19.i13.2060] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2012] [Revised: 01/04/2013] [Accepted: 01/24/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the association between atrophic gastritis (AG) and esophageal squamous cell carcinoma (ESCC) in a Latin-America population.
METHODS: A case-control study was performed at two reference Brazilian hospitals including patients diagnosed with advanced ESCC and dyspeptic patients who had been subjected to upper gastrointestinal endoscopy, with biopsies of the gastric antrum and body. All cases with ESCC were reviewed by a single pathologist, who applied standard criteria for the diagnosis of mucosal atrophy, intestinal metaplasia, and dysplasia, all classified as AG. The data on the patients’ age, sex, smoking status, and alcohol consumption were collected from clinical records, and any missing information was completed by telephone interview. The association between AG and ESCC was assessed by means of univariate and multiple conditional logistic regressions.
RESULTS: Most patients were male, and the median age was 59 years (range: 37-79 years) in both the ESCC and control groups. Univariate analysis showed that an intake of ethanol greater than 32 g/d was an independent risk factor that increased the odds of ESCC 7.57 times (P = 0.014); upon multiple analysis, alcohol intake of ethanol greater than 32 g/d exhibited a risk of 4.54 (P = 0.081), as adjusted for AG and smoking. Smoking was shown to be an independent risk factor that increased the odds of ESCC 14.55 times (P = 0.011) for individuals who smoked 0 to 51 packs/year and 21.40 times (P = 0.006) for those who smoked more than 51 packs/year. Upon multiple analyses, those who smoked up to 51 packs/year exhibited a risk of 7.85 (P = 0.058), and those who smoked more than 51 packs/ year had a risk 11.57 times higher (P = 0.04), as adjusted for AG and alcohol consumption. AG proved to be a risk factor that increased the odds of ESCC 5.33 times (95%CI: 1.55-18.30, P = 0.008) according to the results of univariate conditional logistic regression.
CONCLUSION: There was an association by univariate conditional logistic regression between AG and ECSS in this sample of Latin-American population.
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Iwai W, Abe Y, Iijima K, Koike T, Uno K, Asano N, Imatani A, Shimosegawa T. Gastric hypochlorhydria is associated with an exacerbation of dyspeptic symptoms in female patients. J Gastroenterol 2013; 48:214-221. [PMID: 22829345 DOI: 10.1007/s00535-012-0634-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2011] [Accepted: 06/18/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gender and gastric acid have been suggested to be independently involved in the pathophysiology of functional dyspepsia, but the interrelationship among gender, dyspeptic symptoms, and gastric acid secretion remains to be evaluated. We sought to explore this issue in dyspeptic patients. METHODS A total of 89 outpatients (male, 36; mean age, 55.6 years) with dyspeptic symptoms were analyzed. The degree of dyspeptic symptoms was evaluated and scored using a symptom questionnaire consisting of 3 subcategories: dysmotility-related symptoms, reflux-related symptoms, and epigastric pain-related symptoms. Stimulated gastric acid secretion was directly measured using an endoscopic gastrin test. RESULTS The total symptom scores and the epigastric pain-related symptom scores were significantly higher in female patients than in male patients. The dysmotility-related and reflux-related symptom scores were also higher, but not significantly, in the female patients. Multiple regression analysis of age, gender, habitual drinking, smoking, Helicobacter pylori infection, and gastric acid secretion revealed that gender and gastric hypochlorhydria, defined as less than 2.1 mEq/10 min in the endoscopic gastrin test, were significantly associated with higher dyspeptic symptom scores. The total scores and the dysmotility-related scores were significantly higher in the patients with gastric hypochlorhydria than in those with gastric non-hypochlorhydria, and this difference was found to be present only in females. CONCLUSIONS Gastric hypochlorhydria in female dyspeptic patients may be involved in the exacerbation of dyspeptic symptoms. Differences in the responsiveness to gastric hypochlorhydria between males and females may be partly responsible for the gender differences in the prevalence and severity of dyspeptic symptoms.
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Affiliation(s)
- Wataru Iwai
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
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17
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Non-acid reflux: the missing link between gastric atrophy and esophageal squamous cell carcinoma? Am J Gastroenterol 2011; 106:1930-2. [PMID: 22056574 DOI: 10.1038/ajg.2011.288] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Esophageal cancer is the eighth most common incident cancer in the world and, due to the poor survival rate it confers, ranks sixth among all cancers in mortality. In developed countries of the western world, the incidence of esophageal squamous cell carcinoma (ESCC) has undergone a decline and adenocarcinoma now constitutes approximately half of all esophageal cancers. In these relatively low-risk areas, tobacco smoking and alcohol consumption account for ~90% of ESCC cases. Eastern countries have much higher incidences of ESCC and epidemiologic evidence would suggest that there are additional unknown causal mechanisms. Gastric atrophy has consistently been associated with ESCC, but its causal relevance has been questioned. In this issue of the American Journal of Gastroenterology, Uno et al. offer evidence that a causal link between these two entities is non-acid reflux.
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18
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Uno K, Iijima K, Hatta W, Koike T, Abe Y, Asano N, Kusaka G, Shimosegawa T. Direct measurement of gastroesophageal reflux episodes in patients with squamous cell carcinoma by 24-h pH-impedance monitoring. Am J Gastroenterol 2011; 106:1923-1929. [PMID: 21931379 DOI: 10.1038/ajg.2011.282] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Recent studies have consistently reported a significant association between gastric atrophy and esophageal squamous cell carcinomas (ESCCs). However, causative factors responsible for the linkage remain to be clarified. Multichannel intraluminal impedance monitoring in conjunction with a pH sensor (MII-pH) is a reliable technique to evaluate gastroesophageal reflux (GER) episodes, independent of the acidity. We investigated the potential roles of GER in the pathogenesis of ESCC with MII-pH. METHODS From August 2008 to May 2010, 14 consecutive inpatients with superficial ESCCs (ESCC group) and 14 age- and sex-matched inpatients without any esophageal dysplastic lesions (non-ESCC group) were enrolled. Twenty-four hour portable MII-pH monitoring was performed under standard hospitalized conditions. The data of MII-pH were used to identify acid reflux (AR: pH drop below 4.0 during a reflux episode) and non-AR (NAR: pH drop above 4.0 during a reflux episode). RESULTS The median intragastric pH of the ESCC group was 4.7 (2.3-6.4), implying hypochlorhydria in this patient group. The numbers of total reflux and NAR episodes in the ESCC group were significantly higher than those in the non-ESCC group (56 (43-87) vs. 35.5 (18-47), P=0.016 for total reflux and 46.5 (32-84) vs. 24.5 (8-37), P=0.012 for NAR), whereas the numbers of AR were similar in both groups. In addition, there was significance in the category of percentage time of bolus reflux episodes. CONCLUSIONS Using MII-pH monitoring, we revealed the clinical significance of GER, especially NAR, in ESCCs. NAR may be a key factor in the link between gastric atrophy and ESCCs.
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Affiliation(s)
- Kaname Uno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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Lochhead P, Frank B, Hold GL, Rabkin CS, Ng MTH, Vaughan TL, Risch HA, Gammon MD, Lissowska J, Weck MN, Raum E, Müller H, Illig T, Klopp N, Dawson A, McColl KE, Brenner H, Chow WH, El-Omar EM. Genetic variation in the prostate stem cell antigen gene and upper gastrointestinal cancer in white individuals. Gastroenterology 2011; 140:435-41. [PMID: 21070776 PMCID: PMC3031760 DOI: 10.1053/j.gastro.2010.11.001] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2010] [Revised: 10/22/2010] [Accepted: 11/03/2010] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS An association between gastric cancer and the rs2294008 (C>T) polymorphism in the prostate stem cell antigen (PSCA) gene has been reported for several Asian populations. We set out to determine whether such an association exists in white individuals. METHODS We genotyped 166 relatives of gastric cancer patients, including 43 Helicobacter pylori-infected subjects with hypochlorhydria and gastric atrophy, 65 infected subjects without these abnormalities, 58 H pylori-negative relatives, and 100 population controls. Additionally, a population-based study of chronic atrophic gastritis provided 533 cases and 1054 controls. We then genotyped 2 population-based, case-control studies of upper gastrointestinal cancer: the first included 312 gastric cancer cases and 383 controls; the second included 309 gastric cancer cases, 159 esophageal cancer cases, and 211 controls. Odds ratios were computed from logistic models and adjusted for confounding variables. RESULTS Carriage of the risk allele (T) of rs2294008 in PSCA was associated with chronic atrophic gastritis (adjusted odds ratio [OR], 1.5; 95% confidence interval [CI]: 1.1-1.9) and noncardia gastric cancer (OR, 1.9; 95% CI: 1.3-2.8). The association was strongest for the diffuse histologic type (OR, 3.2; 95% CI: 1.2-10.7). An inverse association was observed between carriage of the risk allele and gastric cardia cancer (OR, 0.5; 95% CI: 0.3-0.9), esophageal adenocarcinoma (OR, 0.5; 95% CI: 0.3-0.9), and esophageal squamous cell carcinoma (OR, 0.4; 95% CI: 0.2-0.9). CONCLUSIONS The rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers.
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Affiliation(s)
- Paul Lochhead
- Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Scotland
| | - Bernd Frank
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Georgina L. Hold
- Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Scotland
| | - Charles S. Rabkin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Michael T. H. Ng
- Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Scotland
| | - Thomas L. Vaughan
- Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, and Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington
| | - Harvey A. Risch
- Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut
| | - Marilie D. Gammon
- Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina
| | - Jolanta Lissowska
- Division of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Melanie N. Weck
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Elke Raum
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Heiko Müller
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Thomas Illig
- Institute of Epidemiology, Research Centre for Environment and Health, Neuherberg, Germany
| | - Norman Klopp
- Institute of Epidemiology, Research Centre for Environment and Health, Neuherberg, Germany
| | - Alan Dawson
- Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Scotland
| | - Kenneth E. McColl
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Wong-Ho Chow
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Emad M. El-Omar
- Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Scotland
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Abstract
PURPOSE OF REVIEW This review summarizes the past year's literature regarding the regulation of gastric exocrine and endocrine secretion at the central, peripheral, and cellular levels. RECENT FINDINGS Gastric acid secretion is an intricate and dynamic process that is regulated by neural (efferent and afferent), hormonal (e.g., gastrin), and paracrine (e.g., histamine, ghrelin, somatostatin) pathways as well as mechanical (e.g., distension) and chemical (e.g., protein, glutamate, coffee, and ethanol) stimuli. Secretion of hydrochloric acid by the parietal cell involves recruitment and fusion of HK-adenosine triphosphatase (HK-ATPase)-containing cytoplasmic tubulovesicles with the apical membrane with subsequent electroneutral transport of hydronium ions in exchange for potassium; the source of the latter is the potassium channel, KCNQ1. Concomitantly, chloride exits via the cystic fibrosis transmembrane regulator. Inhibition of the HK-ATPase by proton pump inhibitors leads to a compensatory hypergastrinemia which, if prolonged, results in parietal and enterochromaffin-like cell hyperplasia. The clinical consequence is rebound acid secretion which may induce dyspeptic symptoms in healthy individuals and exacerbate reflux symptoms in patients with gastroesophageal reflux disease. SUMMARY We continue to make progress in our understanding of the regulation of gastric acid secretion in health and disease. A better understanding of the pathways and mechanisms regulating acid secretion should lead to improved management of patients with acid-induced disorders as well as those who secrete too little acid.
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Oikawa T, Iijima K, Koike T, Uno K, Horii T, Iwai W, Abe Y, Asano N, Imatani A, Shimosegawa T. Deficient aldehyde dehydrogenase 2 is associated with increased risk for esophageal squamous cell carcinoma in the presence of gastric hypochlorhydria. Scand J Gastroenterol 2010; 45:1338-1344. [PMID: 20521872 DOI: 10.3109/00365521.2010.495419] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE In Orientals, deficient aldehyde dehydrogenase 2 (ALDH2) is associated with an increased risk for esophageal squamous cell carcinoma (ESCC). The local metabolism of carcinogenic acetaldehyde in the upper gastrointestinal tract could be involved in the association, but the underlying mechanism has not been fully elucidated. Since an anacidic stomach can promote bacteria-catalyzed local acetaldehyde production, the gastric acid level could also affect acetaldehyde metabolism. This study investigated whether ALDH2-related susceptibility to ESCC differs depending on the gastric secretion level. MATERIAL AND METHODS Sixty-two patients with ESCC and sex- and age-matched normal controls were enrolled in this study. ALDH2 polymorphism was analyzed by polymerase chain-restriction fragment length polymorphism, and those with an inactive allele (ALDH2-1/2-2 or ALDH2-2/2-2) were defined as ALDH2 deficient. Gastrin-stimulated acid output was assessed by endoscopic gastrin test and hypochlorhydria was defined as 0.6 mEq/10 min or lower. Multiple logistic regression analyses were used to adjust for other potential confounders. RESULTS ALDH2 deficiency or hypochlorhydria was more prevalent in ESCC compared with controls and both showed increased independent associations with ESCC in multivariate analysis. Stratified analysis by the gastric acid secretion level revealed that the associations between the ALDH2 genotype and ESCC differed according to the individual gastric acid secretion levels and that ALDH2 deficiency was a significant risk factor for ESCC exclusively in individuals with hypochlorhydria with an odds ratio (95% confidence interval): 5.0 (1.2-21.2). CONCLUSION Microbial production of carcinogen acetaldehyde in the presence of gastric hypochlorhydria is most probably involved in the mechanism of ALDH2-related susceptibility to ESCC.
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Affiliation(s)
- Tomoyuki Oikawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aobaku, Sendai, Japan
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22
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Islami F, Sheikhattari P, Ren JS, Kamangar F. Gastric atrophy and risk of oesophageal cancer and gastric cardia adenocarcinoma--a systematic review and meta-analysis. Ann Oncol 2010; 22:754-760. [PMID: 20860989 DOI: 10.1093/annonc/mdq411] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Several studies have reported an association between gastric atrophy and upper gastrointestinal cancers. Our aim was to summarise the available information and calculate the relative risks (RRs) associated with gastric atrophy for gastric cardia adenocarcinoma (GCA), oesophageal squamous cell carcinoma (OSCC), and oesophageal adenocarcinoma (OAC) by conducting a systematic review and meta-analysis. METHODS We searched the PubMed and ISI-Web of Science databases, as well as the reference lists of the relevant articles. Summary RRs and 95% confidence intervals (95% CI) were calculated using random-effects models for the association between gastric atrophy, defined histologically or by serum pepsinogen markers, and OSCC, OAC, and GCA. RESULTS Eighteen articles were included in the meta-analysis; 13, 7, and 3 studies reported on GCA, OSCC, and OAC, respectively. The overall RRs (95% CI) for the three cancer types were: GCA, 2.89 (2.09-3.98); OSCC, 1.94 (1.48-2.55); OAC, 0.51 (0.19-1.37). Several subgroup analyses showed the robustness of the results. In the majority of the analyses, there was low to moderate heterogeneity. CONCLUSIONS This study found two- to threefold increased risk of OSCC and GCA but a possible reduced risk of OAC in people with gastric atrophy. Further studies are needed to establish the association with OAC and causal association with OSCC, and mechanisms of the increased risk need to be investigated for GCA.
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Affiliation(s)
- F Islami
- Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical sciences, Tehran, Iran; International Agency for Research on Cancer, Lyon, France; King's College London, Thames Cancer Registry, London, UK
| | - P Sheikhattari
- Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, USA
| | - J S Ren
- International Agency for Research on Cancer, Lyon, France
| | - F Kamangar
- Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, USA; Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical sciences, Tehran, Iran.
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Cook MB, Dawsey SM, Diaw L, Blaser MJ, Perez-Perez GI, Abnet CC, Taylor PR, Albanes D, Virtamo J, Kamangar F. Serum pepsinogens and Helicobacter pylori in relation to the risk of esophageal squamous cell carcinoma in the alpha-tocopherol, beta-carotene cancer prevention study. Cancer Epidemiol Biomarkers Prev 2010; 19:1966-75. [PMID: 20647397 DOI: 10.1158/1055-9965.epi-10-0270] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Helicobacter pylori can induce gastric atrophy in humans, which in turn increases gastric cancer risk. Whether H. pylori and gastric atrophy also affect the risk of esophageal squamous cell carcinoma (ESCC), however, remains unresolved. METHODS We performed a nested case-control study within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to assess these relationships. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study is composed of 29,133 Finnish male smokers, ages 50 to 69 years, who were recruited during 1985-1988. Using baseline sera, we assessed H. pylori status (via immunoglobulin G antibodies against whole-cell and CagA antigens) and gastric atrophy status [via the biomarkers pepsinogen I (PGI) and pepsinogen II (PGII)] in 79 ESCC cases and 94 controls. Logistic regression with adjustment for age, date of blood draw, education, cigarette smoking, alcohol, body mass index, and fruit and vegetable intake was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS Gastric atrophy (PGI/PGII <4) was associated with ESCC (OR, 4.58; 95% CI, 2.00-10.48). There was no evidence for an association between H. pylori and ESCC (OR, 0.94; 95% CI, 0.40-2.24). CONCLUSIONS These results could be explained by misclassification of H. pylori status due to serologic amnesia, ESCC risk being dependent on the functional consequences or interactions of H. pylori rather than the infection per se, gastric atrophy having a different histogenesis in ESCC without being primarily dependent on H. pylori acquisition, or a lack of statistical power to detect an effect. IMPACT Validation of these results may warrant mechanistic studies to determine the route of association between gastric atrophy and ESCC.
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Affiliation(s)
- Michael B Cook
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, 6120 Executive Boulevard, Bethesda, MD 20852-7234, USA.
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