|
1
|
Zhao SQ, Zheng HL, Zhong XT, Wang ZY, Su Y, Shi YY. Effects and mechanisms of Helicobacter pylori infection on the occurrence of extra-gastric tumors. World J Gastroenterol 2024; 30:4090-4103. [DOI: 10.3748/wjg.v30.i37.4090] [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] [Received: 04/09/2024] [Revised: 08/23/2024] [Accepted: 09/12/2024] [Indexed: 09/26/2024] Open
Abstract
Helicobacter pylori (H. pylori) colonizes the human stomach and many studies have discussed the mechanisms of H. pylori infection leading to gastric diseases, including gastric cancer. Additionally, increasing data have shown that the infection of H. pylori may contribute to the development of extra-gastric diseases and tumors. Inflammation, systemic immune responses, microbiome disorders, and hypergastrinemia caused by H. pylori infection are associated with many extra-gastric malignancies. This review highlights recent discoveries; discusses the relationship between H. pylori and various extra-gastric tumors, such as colorectal cancer, lung cancer, cholangiocarcinoma, and gallbladder carcinoma; and explores the mechanisms of extra-gastric carcinogenesis by H. pylori. Overall, these findings refine our understanding of the pathogenic processes of H. pylori, provide guidance for the clinical treatment and management of H. pylori-related extra-gastric tumors, and help improve prognosis.
Collapse
Affiliation(s)
- Shi-Qing Zhao
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Hui-Ling Zheng
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Xiao-Tian Zhong
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Zi-Ye Wang
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Yi Su
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Yan-Yan Shi
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
| |
Collapse
|
|
2
|
Luo F, Zhou P, Ran X, Gu M, Zhou S. No evident causal association between Helicobacter pylori infection and colorectal cancer: a bidirectional mendelian randomization study. Sci Rep 2023; 13:18544. [PMID: 37899462 PMCID: PMC10613620 DOI: 10.1038/s41598-023-45545-x] [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: 09/30/2023] [Accepted: 10/20/2023] [Indexed: 10/31/2023] Open
Abstract
Observational studies have reported a correlation between Helicobacter pylori infection and colorectal cancer (CRC); however, the underlying cause has remained unclear. This research was aimed at determining whether there is a correlation between H. pylori infection and CRC by measuring the prevalence of H. pylori CagA antibodies and VacA antibodies. Using data from many genome-wide association studies (GWAS), we conducted a Mendelian randomization (MR) study with two sample GWAS. Then, we used bidirectional MR to evaluate the association between H. pylori infection and CRC for identifying causation. The most common method of analysis was the inverse variance-weighted technique. In addition, we performed supplementary analyses using the weighted median technique and MR-Egger regression. Horizontal pleiotropic outliers were identified and corrected using the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) method. Genetically predicted anti-H. pylori IgG seropositivity was not causally associated with CRC [odds ratio (OR): 1.12; 95% confidence interval (CI): 0.98-1.27, P = 0.08] and neither were H. pylori VacA antibody levels (OR = 0.96, 95% CI: 0.90-1.02, P = 0.25) or H. pylori CagA antibody levels (OR = 1.00, 95% CI: 0.93-1.07, P = 0.92). Furthermore, reverse MR analysis did not reveal evidence for a causal effect of CRC on H. pylori infection. The weighted median, the MR-Egger method, and MR-PRESSO yielded identical results. Using genetic data, MR analysis showed there was no evidence for a causal association between seroprevalence of H. pylori infection and CRC. The relationship between H. pylori infection and CRC requires further research.
Collapse
Affiliation(s)
- Fang Luo
- Department of Gastroenterology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021, China
| | - Peipei Zhou
- Department of Gastroenterology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021, China
| | - Xiong Ran
- Department of Radiology, Chongqing General Hospital, No.118, Xingguang Avenue, Liangjiang New District, Chongqing, 400014, China
| | - Ming Gu
- Department of Radiology, Chongqing General Hospital, No.118, Xingguang Avenue, Liangjiang New District, Chongqing, 400014, China.
| | - Shaoquan Zhou
- Department of Radiology, Chongqing General Hospital, No.118, Xingguang Avenue, Liangjiang New District, Chongqing, 400014, China.
| |
Collapse
|
|
3
|
Wu X, Peng B, Qian K, Zhang W, Min J, Zhang M, Zeng F, Wang Z. The combination of methylenehydrofolate reductase C677T polymorphism screening and gastrointestinal tumor markers detection may be an early screening method for gastrointestinal cancer related to helicobacter pylori infection. Genes Dis 2021; 8:931-938. [PMID: 34522719 PMCID: PMC8427234 DOI: 10.1016/j.gendis.2021.02.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 02/20/2021] [Accepted: 02/21/2021] [Indexed: 01/12/2023] Open
Abstract
Methyltetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism, and its single nucleotide polymorphism (SNP) site C677T may be associated with gastrointestinal cancer. However, the relationship between MTHFR C677T polymorphism and gastrointestinal tumor markers carcinoma embryonic antigen (CEA), carbohydrate antigen 199 (CA199) and carbohydrate antigen 724 (CA724) in Helicobacter pylori (H. pylori) infection is not specified. This study aims to identify the association between MTHFR C677T polymorphism and gastrointestinal tumor markers (CEA, CA199 and CA724) in H. pylori infection. The relationship between MTHFR C677T polymorphism and gastrointestinal tumor markers in 58 patients with H. pylori infection and 94 non-infected patients was studied. We found that TT genotype was a susceptibility factor of H. pylori infection, which was also associated with increased CEA and CA724 levels. Moreover, there was a negative additive interaction between MTHFR gene C677T polymorphism and CEA levels in H.pylori infection. Meanwhile, there were significant differences in CEA levels between MTHFR C677T polymorphism and H.pylori infection. The presence of T allele led to a decrease in CEA levels when 13C urea breath test (13C-UBT) was positive, while the presence of T allele led to an increase in CEA levels when 13C-UBT was negative. Therefore, we suggest that healthy people should take MTHFR C677T polymorphism screening, combined with 13C-UBT and gastrointestinal tumor markers detection, which can screen out the susceptible population of H. pylori, and help to detect gastrointestinal cancer in the early stage.
Collapse
Affiliation(s)
- Xiaoxing Wu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China
| | - Bin Peng
- School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, PR China
| | - Kun Qian
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China
| | - Wei Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China
| | - Jiang Min
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China
| | - Mingjun Zhang
- Health Management Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China
| | - Fanling Zeng
- Health Management Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China
| | - Ziwei Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China
| |
Collapse
|
|
4
|
Chen QF, Zhou XD, Fang DH, Zhang EG, Lin CJ, Feng XZ, Wang N, Wu JS, Wang D, Lin WH. Helicobacter pylori infection with atrophic gastritis: An independent risk factor for colorectal adenomas. World J Gastroenterol 2020; 26:5682-5692. [PMID: 33088161 PMCID: PMC7545385 DOI: 10.3748/wjg.v26.i37.5682] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 05/29/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The significance of Helicobacter pylori (H. pylori) infection and atrophic gastritis (AG) in the prevalence of colorectal adenomas has been examined in a limited number of studies. However, these studies reported disputed conclusions.
AIM To investigate whether H. pylori infection, AG, and H. pylori-related AG increase the risk of colorectal adenomas.
METHODS This retrospective cross-sectional study included 6018 health-check individuals. The relevant data for physical examination, laboratory testing, 13C-urea breath testing, gastroscopy, colonoscopy and histopathological examination of gastric and colorectal biopsies were recorded. Univariate and multivariate logistic regression analyses were performed to determine the association between H. pylori-related AG and colorectal adenomas.
RESULTS Overall, 1012 subjects (16.8%) were diagnosed with colorectal adenomas, of whom 143 (2.4%) had advanced adenomas. Among the enrolled patients, the prevalence of H. pylori infection and AG was observed as 49.5% (2981/6018) and 10.0% (602/6018), respectively. Subjects with H. pylori infection had an elevated risk of colorectal adenomas (adjusted odds ratio [OR] of 1.220, 95% confidence interval (CI): 1.053-1.413, P = 0.008) but no increased risk of advance adenomas (adjusted OR = 1.303, 95%CI: 0.922-1.842, P = 0.134). AG was significantly correlated to an increased risk of colorectal adenomas (unadjusted OR = 1.668, 95%CI: 1.352-2.059, P < 0.001; adjusted OR = 1.237, 95%CI: 0.988-1.549, P = 0.064). H. pylori infection accompanied by AG was significantly associated with an increased risk of adenomas (adjusted OR = 1.491, 95%CI: 1.103-2.015, P = 0.009) and advanced adenomas (adjusted OR = 1.910, 95%CI: 1.022-3.572, P = 0.043).
CONCLUSION H. pylori-related AG was associated with a high risk of colorectal adenomas and advanced adenomas in Chinese individuals.
Collapse
Affiliation(s)
- Qin-Fen Chen
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Xiao-Dong Zhou
- Department of Cardiovascular Medicine, The Key Laboratory of Cardiovascular Diseases of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Dan-Hong Fang
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - En-Guang Zhang
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Chun-Jing Lin
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Xiao-Zhen Feng
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Na Wang
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Jian-Sheng Wu
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Dan Wang
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Wei-Hong Lin
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| |
Collapse
|
|
5
|
Wang M, Kong WJ, Zhang JZ, Lu JJ, Hui WJ, Liu WD, Kang XJ, Gao F. Association of Helicobacter pylori infection with colorectal polyps and malignancy in China. World J Gastrointest Oncol 2020; 12:582-591. [PMID: 32461789 PMCID: PMC7235179 DOI: 10.4251/wjgo.v12.i5.582] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 03/13/2020] [Accepted: 03/24/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Gastric Helicobacter pylori (H. pylori) infection is related to chronic gastritis, gastroduodenal ulcer, and gastric malignancies; whether this infection is related to colorectal polyps and colorectal cancer (CRC), remains debatable. AIM To investigate the relationship between gastric H. pylori infection and the risk of colorectal polyps and CRC. METHODS We retrospectively analyzed 3872 patients with colorectal polyps who underwent colonoscopy and pathological diagnosis. We also analyzed 304 patients with primary CRC. The characteristics of these patients were compared with those of the control group, which included 2362 patients with the normal intestinal mucosa. All subjects completed a 14C-urea breath test, bidirectional gastrointestinal endoscopy, and a biopsy on the same day. Data on the number, size, location, and pathology of the polyps, the location, and pathology of the CRC, the detection of H. pylori, and the incidence of H. pylori-associated atrophic gastritis or intestinal metaplasia were obtained. A logistic regression model was used to analyze the relationship between gastric infection due to H. pylori, and the incidence of colorectal polyps and CRC. RESULTS The prevalence of H. pylori infection was higher in the multiple polyps group than in the solitary polyp group and the control group [95% confidence interval (CI) = 1.02-1.31, P = 0.03; 95%CI: 2.12-2.74, P < 0.001]. The patients with adenomatous polyps had a higher incidence of H. pylori infection than patients with non-adenomatous polyps [59.95% vs 51.75%, adjusted odds ratio (OR) = 1.41, 95%CI: 1.24-1.60, P < 0.01]. Patients with H. pylori-associated atrophic gastritis or intestinal metaplasia were at high risk of CRC (adjusted OR = 3.46, 95%CI: 2.63-4.55, P < 0.01; adjusted OR = 4.86, 95%CI: 3.22-7.34, P < 0.01, respectively). The size and location of the polyps, the histopathological characteristics and the location of CRC were not related to H. pylori infection. CONCLUSION Our study demonstrates that the incidence of gastric H. pylori infection and H. pylori-associated atrophic gastritis or intestinal metaplasia elevates the risk of colorectal polyps and CRC.
Collapse
Affiliation(s)
- Man Wang
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Wen-Jie Kong
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Jing-Zhan Zhang
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Jia-Jie Lu
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Wen-Jia Hui
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Wei-Dong Liu
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Xiao-Jing Kang
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Feng Gao
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| |
Collapse
|