Helicobacter pylori antibody responses and evolution of precancerous gastric lesions in a Chinese population
Kai-Feng Pan
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Conflict of interest: Nothing to report
Search for more papers by this authorLuca Formichella
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
Search for more papers by this authorLian Zhang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorYang Zhang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorJun-Ling Ma
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorZhe-Xuan Li
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorCong Liu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorYu-Mei Wang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorKurt Ulm
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
Search for more papers by this authorMeinhard Classen
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
Search for more papers by this authorCorresponding Author
Wei-Cheng You
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Correspondence to: Markus Gerhard, MD, Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany, E-mail: [email protected] or Wei-Cheng You, MD, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, People's Republic of China, E-mail: [email protected]Search for more papers by this authorCorresponding Author
Markus Gerhard
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
DZIF German Centre for Infection Research, München, Germany
Correspondence to: Markus Gerhard, MD, Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany, E-mail: [email protected] or Wei-Cheng You, MD, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, People's Republic of China, E-mail: [email protected]Search for more papers by this authorKai-Feng Pan
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Conflict of interest: Nothing to report
Search for more papers by this authorLuca Formichella
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
Search for more papers by this authorLian Zhang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorYang Zhang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorJun-Ling Ma
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorZhe-Xuan Li
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorCong Liu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorYu-Mei Wang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Search for more papers by this authorKurt Ulm
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
Search for more papers by this authorMeinhard Classen
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
Search for more papers by this authorCorresponding Author
Wei-Cheng You
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
Correspondence to: Markus Gerhard, MD, Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany, E-mail: [email protected] or Wei-Cheng You, MD, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, People's Republic of China, E-mail: [email protected]Search for more papers by this authorCorresponding Author
Markus Gerhard
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany
DZIF German Centre for Infection Research, München, Germany
Correspondence to: Markus Gerhard, MD, Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany, E-mail: [email protected] or Wei-Cheng You, MD, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, People's Republic of China, E-mail: [email protected]Search for more papers by this authorAbstract
Helicobacter pylori-specific proteins are involved in gastric carcinogenesis. To investigate the seroprevalence of six H. pylori-specific antibodies in patients with different gastric histology, and the impact of seropositivities on the evolution of precancerous gastric lesions, a follow-up study was conducted in Linqu County, China. The seropositivities for CagA, VacA, GroEL, UreA, HcpC and gGT were assessed by recomLine analysis in 573 H. pylori-positive subjects and correlated with evolution of precancerous gastric lesions. We found that the score of H. pylori recomLine test was significantly increased in subjects with chronic atrophic gastritis (CAG, p < 0.0001) or intestinal metaplasia (IM, p = 0.0125), and CagA was an independent predictor of advanced gastric lesions, adjusted odds ratios (ORs) were 2.54 (95% CI = 1.42–4.55) for IM and 2.38 (95% CI = 1.05–5.37) for dysplasia (DYS). Moreover, seropositivities for CagA and GroEL were identified as independent predictors for progression of gastric lesions in a longitudinal study, and ORs were 2.89 (95% CI = 1.27–6.59) and 2.20 (95% CI = 1.33–3.64), respectively. Furthermore, the risk of progression was more pronounced in subjects with more than three positive antigens (pfor trend = 0.0003). This population-based study revealed that seropositivities for CagA and GroEL might be potential markers to identify patients infected with high-risk H. pylori strains, which are related to the development of GC in a Chinese high-risk population, and recomLine test might serve as a tool for risk stratification.
Abstract
What's new?
The bacteria H. pylori is the strongest known risk factor for gastric cancer, but only a small percentage of those infected ever develop cancer. To help predict who those will be, researchers have identified several markers that associate with gastric cancer. This study sought to expand on earlier data associating the presence of antibodies to these markers with the risk of developing gastric lesions and cancer in a high-risk population. Patients with antibodies for either CagA and GroEL were more likely to have gastric lesions progress to cancer, as were people who had antibodies for more than three markers. These tests could be useful in assessing risk among those with H. pylori infections.
Supporting Information
Additional Supporting Information may be found in the online version of this article
| Filename | Description |
|---|---|
| ijc28560-sup-0001-supptable1.docx18.3 KB | Supporting Information Table 1. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med 2002; 347: 1175-86.
- 2Correa P. A human model of gastric carcinogenesis. Cancer Res 1988; 48: 3554-60.
- 3Peek RM, Blaser M. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer 2002; 2: 28-37.
- 4You WC, Brown LM, Zhang L, et al. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst 2006; 98: 974-83.
- 5Ma JL, Zhang L, Brown LM, et al. Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. J Natl Cancer Inst 2012; 104: 488-92.
- 6Wong BC, Zhang L, Ma JL, et al. Effects of selective COX-2 inhibitor and Helicobacter pylori eradication on precancerous gastric lesions. Gut 2012; 61: 812-18.
- 7Polk DB, Peek RM. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer 2010; 10: 403-14.
- 8Correa P, Houghton J. Carcinogenesis of Helicobacter pylori. Gastroenterology 2007; 133: 659-72.
- 9Blaser MJ. Disappearing microbiota: Helicobacter pylori protection against esophageal adenocarcinoma. Cancer Prev Res (Phila) 2008; 1: 308-11.
- 10Wu W, Yang Y, Sun G. Recent insights into antibiotic resistance in Helicobacter pylori eradication. Gastroenterol Res Pract 2012; 2012: 723183.
- 11Hocker M, Hohenberger P. Helicobacter pylori virulence factors—one part of a big picture. Lancet 2003; 362: 1231-3.
- 12Huang JQ, Zheng GF, Sumanac K, et al. Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 2003; 125: 1636-44.
- 13Gao L, Michel A, Weck MN, et al. Helicobacter pylori infection and gastric cancer risk: evaluation of 15 H. pylori proteins determined by novel multiplex serology. Cancer Res 2009; 69: 6164-70.
- 14Gao L, Weck MN, Michel A, et al. Association between chronic atrophic gastritis and serum antibodies to 15 Helicobacter pylori proteins measured by multiplex serology. Cancer Res 2009; 69: 2973-80.
- 15Formichella L, Romberg L, Bolz C, et al. A novel immuno-line assay based on recombinant virulence factors enables highly specific and sensitive serological diagnosis of H. pylori infection. Clin Vaccine Immunol 2013; 20: 1703-1710.
- 16You WC, Blot WJ, Li JY, et al. Precancerous gastric lesions in a population at high risk of stomach cancer. Cancer Res 1993; 53: 1317-21.
- 17Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 1996; 20: 1161-81.
- 18Rugge M, Correa P, Dixon MF, et al. Gastric dysplasia: the Padova international classification. Am J Surg Pathol 2000; 24: 167-76.
- 19Klein PD, Malaty HM, Martin RF, et al. Noninvasive detection of Helicobacter pylori infection in clinical practice: the 13C urea breath test. Am J Gastroenterol 1996; 91: 690-4.
- 20You WC, Zhang L, Gail MH, et al. Helicobacter pylori infection, garlic intake and precancerous lesions in a Chinese population at low risk of gastric cancer. Int J Epidemiol 1998; 27: 941-4.
- 21Ji J, Zhen WS, Ming LX, et al. The modification of 13C-Urea Breath Test. Zhonghuaheyixuezaizhi 1994; 14: 103-5.
- 22Zhang L, Blot WJ, You WC, et al. Helicobacter pylori antibodies in relation to precancerous gastric lesions in a high-risk Chinese population. Cancer Epidemiol Biomarkers Prev 1996; 5: 627-30.
- 23Tu HK, Pan KF, Zhang Y, et al. Manganese superoxide dismutase polymorphism and risk of gastric lesions, and its effects on chemoprevention in a Chinese population. Cancer Epidemiol Biomarkers Prev 2010; 19: 1089-97.
- 24Fock KM, Ang TL. Epidemiology of Helicobacter pylori infection and gastric cancer in Asia. J Gastroenterol Hepatol 2010; 25: 479-86.
- 25Vilaichone RK, Mahachai V, Tumwasorn S, et al. Molecular epidemiology and outcome of Helicobacter pylori infection in Thailand: a cultural cross roads. Helicobacter 2004; 9: 453-9.
- 26Groves FD, Perez-Perez G, Zhang L, et al. Serum antibodies to Helicobacter pylori and the CagA antigen do not explain differences in the prevalence of precancerous gastric lesions in two Chinese populations with contrasting gastric cancer rates. Cancer Epidemiol Biomarkers Prev 2002; 11: 1091-4.
- 27You W-C, Zhang L, Pan K-F, et al. Helicobacter pylori prevalence and CagA status among children in two counties of china with high and low risks of gastric cancer. Ann Epidemiol 2001; 11: 543-6.
- 28Dunn BE, Roop RM, II, Sung CC, et al. Identification and purification of a cpn60 heat shock protein homolog from Helicobacter pylori. Infect Immun 1992; 60: 1946-51.
- 29Vanet A, Labigne A. Evidence for specific secretion rather than autolysis in the release of some Helicobacter pylori proteins. Infect Immun 1998; 66: 1023-7.
- 30Bergonzelli GE, Granato D, Pridmore RD, et al. GroEL of Lactobacillus johnsonii La1 (NCC 533) is cell surface associated: potential role in interactions with the host and the gastric pathogen Helicobacter pylori. Infect Immun 2006; 74: 425-34.
- 31Macchia G, Massone A, Burroni D, et al. The Hsp60 protein of Helicobacter pylori: structure and immune response in patients with gastroduodenal diseases. Mol Microbiol 1993; 9: 645-52.
- 32Kamoshida S, Satoh Y, Kamiya S, et al. Heat shock protein 60 (HSP60) immunoreactivity in gastric epithelium associated with Helicobacter pylori infection: a pitfall in immunohistochemically interpreting HSP60-mediated autoimmune responses. Pathol Int 1999; 49: 88-90.
- 33Yamaguchi H, Osaki T, Kai M, et al. Immune response against a cross-reactive epitope on the heat shock protein 60 homologue of Helicobacter pylori. Infect Immun 2000; 68: 3448-54.
- 34Schmees C, Prinz C, Treptau T, et al. Inhibition of T-cell proliferation by Helicobacter pylori gamma-glutamyl transpeptidase. Gastroenterology 2007; 132: 1820-33.
- 35Gong M, Ling SSM, Lui SY, et al. Helicobacter pylori γ-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease. Gastroenterology 2010; 139: 564-73.
Citing Literature
