The role of Helicobacter in gastric cancer prevention
DOI:
https://doi.org/10.18203/2394-6040.ijcmph20252924Keywords:
Helicobacter pylori, H. pylori, Gastric cancer, Prevention, H. pylori eradication, H. pylori vaccinationAbstract
Gastric cancer is one of the most common cancers worldwide. It is associated with high mortality risk. Helicobacter pylori (H. pylori) is a major significant risk factor for gastric cancer, as its virulence factors significantly contribute to gastric carcinogenesis. H. pylori eradication has been associated with reduced incidence of gastric cancer. H. pylori mechanisms in achieving long-term and sustained cancer prevention remain unclear. The aim of this review is to explore the effectiveness and mechanisms of H. pylori in gastric cancer prevention. H. pylori contribute to gastric cancer by molecular mechanisms, such as activating the NF-κB pathway, and cellular mechanisms, such as oxidative stress. Studies have shown that H. pylori eradication reduced the incidence of gastric cancer in healthy populations and patients with early gastric cancer undergoing endoscopic mucosal resection. H. pylori vaccination can be an effective method in the prevention of H. pylori infection, thus preventing gastric cancer. Future studies should develop an integrated approach combining targeted eradication, microbiome management, and innovative vaccination strategies to prevent the occurrence of gastric cancer.
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Bray F, Laversanne M, Sung H. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Canc J Clin. 2024;74(3):229-63. DOI: https://doi.org/10.3322/caac.21834
Liu Z, Xu H, You W, Pan K, Li W. Helicobacter pylori eradication for primary prevention of gastric cancer: progresses and challenges. J Nat Cancer Center. 2024;4(4):299-310. DOI: https://doi.org/10.1016/j.jncc.2024.06.006
Hooi JKY, Lai WY, Ng WK. Global prevalence of helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017;153(2):420-9. DOI: https://doi.org/10.1053/j.gastro.2017.04.022
Chen YC, Malfertheiner P, Yu HT. Global prevalence of Helicobacter pylori Infection and incidence of gastric cancer between 1980 and 2022. Gastroenterology. 2024;166(4):605-19. DOI: https://doi.org/10.1053/j.gastro.2023.12.022
Tan P, Yeoh KG. Genetics and molecular pathogenesis of gastric adenocarcinoma. Gastroenterology. 2015;149(5):1153-62. DOI: https://doi.org/10.1053/j.gastro.2015.05.059
Gu J, He F, Clifford GM. A systematic review and meta-analysis on the relative and attributable risk of Helicobacter pylori infection and cardia and non-cardia gastric cancer. Expert Rev Molec Diagnos. 2023;23(12):1251-61. DOI: https://doi.org/10.1080/14737159.2023.2277377
Gu Y, Xu Y, Wang P, Zhao Y, Wan C. Research progress on molecular mechanism of pyroptosis caused by Helicobacter pylori in gastric cancer. Ann Med Surg. 2024;86(4):2016-22. DOI: https://doi.org/10.1097/MS9.0000000000001802
You WC, Zhang L, Gail MH, et al. Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors. J National Canc Institute. 2000;92(19):1607-12. DOI: https://doi.org/10.1093/jnci/92.19.1607
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process. First American cancer society award lecture on cancer epidemiology and prevention. Cancer Res. 1992;52(24):6735-40.
IARC. Schistosomes, liver flukes and Helicobacter pylori. IARC monographs on the evaluation of carcinogenic risks to humans. IARC Monog Eval Carci Risks Humans. 1994;61:218-21.
Pan KF, Li WQ, Zhang L. Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial. Nature Med. 2024;30(11):3250-60. DOI: https://doi.org/10.1038/s41591-024-03153-w
Correa P, Fontham ET, Bravo JC. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. J National Can Inst. 2000;92(23):1881-8. DOI: https://doi.org/10.1093/jnci/92.23.1881
Choi IJ, Kim CG, Lee JY. Family History of Gastric Cancer and Helicobacter pylori Treatment. The New England J Med. 2020;382(5):427-36. DOI: https://doi.org/10.1056/NEJMoa1909666
Fukase K, Kato M, Kikuchi S. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet (London, England). 2008;372(9636):392-7. DOI: https://doi.org/10.1016/S0140-6736(08)61159-9
Choi JM, Kim SG, Choi J. Effects of Helicobacter pylori eradication for metachronous gastric cancer prevention: a randomized controlled trial. Gastrointestinal Endos. 2018;88(3):475-85. DOI: https://doi.org/10.1016/j.gie.2018.05.009
Duan Y, Xu Y, Dou Y, Xu D. Helicobacter pylori and gastric cancer: mechanisms and new perspectives. J Hematol Oncol. 2025;18(1):10. DOI: https://doi.org/10.1186/s13045-024-01654-2
Cury B, Megid T, Farooq AR, Wang X, Elimova E. Gastric Cancer: Molecular Mechanisms, Novel Targets, and Immunotherapies: From Bench to Clinical Therapeutics. Cancers. 2023;15(20):587. DOI: https://doi.org/10.3390/cancers15205075
Kitamura H, Ohno Y, Toyoshima Y. Interleukin-6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy. Cancer Sci. 2017;108(10):1947-52. DOI: https://doi.org/10.1111/cas.13332
Jackson CB, Judd LM, Menheniott TR. Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression. J Pathol. 2007;213(2):140-51. DOI: https://doi.org/10.1002/path.2218
Bronte-Tinkew DM, Terebiznik M, Franco A. Helicobacter pylori cytotoxin-associated gene A activates the signal transducer and activator of transcription 3 pathway in vitro and in vivo. Cancer Res. 2009;69(2):632-9. DOI: https://doi.org/10.1158/0008-5472.CAN-08-1191
Tye H, Jenkins BJ. Tying the knot between cytokine and toll-like receptor signaling in gastrointestinal tract cancers. Cancer science. 2013;104(9):1139-45. DOI: https://doi.org/10.1111/cas.12205
Guo Q, Jin Y, Chen X. NF-κB in biology and targeted therapy: new insights and translational implications. Signal transduction and targeted therapy. 2024;9(1):53. DOI: https://doi.org/10.1038/s41392-024-01757-9
Lamb A, Chen LF. Role of the Helicobacter pylori-induced inflammatory response in the development of gastric cancer. J Cell Biochem. 2013;114(3):491-7. DOI: https://doi.org/10.1002/jcb.24389
Brandt S, Kwok T, Hartig R, König W, Backert S. NF-kappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(26):9300-5. DOI: https://doi.org/10.1073/pnas.0409873102
Cao L, Zhu S, Lu H. Helicobacter pylori-induced RASAL2 Through Activation of Nuclear Factor-κB Promotes Gastric Tumorigenesis via β-catenin Signaling Axis. Gastroenterology. 2022;162(6):1716-31. DOI: https://doi.org/10.1053/j.gastro.2022.01.046
Karin M. Nuclear factor-kappaB in cancer development and progression. Nature. 2006;441(7092):431-6. DOI: https://doi.org/10.1038/nature04870
Liu J, Xiao Q, Xiao J. Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal transduction and targeted therapy. 2022;7(1):3. DOI: https://doi.org/10.1038/s41392-021-00762-6
Wu S, Chen Y, Chen Z. Reactive oxygen species and gastric carcinogenesis: The complex interaction between Helicobacter pylori and host. Helicobacter. 2023;28(6):e13024. DOI: https://doi.org/10.1111/hel.13024
Ding SZ, Minohara Y, Fan XJ. Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells. Infect Imm. 2007;75(8):4030-9. DOI: https://doi.org/10.1128/IAI.00172-07
Hartog G, Chattopadhyay R, Ablack A. Regulation of Rac1 and Reactive Oxygen Species Production in Response to Infection of Gastrointestinal Epithelia. PLoS Pathog. 2016;12(1):1005382. DOI: https://doi.org/10.1371/journal.ppat.1005382
Fujii Y, Murata-Kamiya N, Hatakeyama M. Helicobacter pylori CagA oncoprotein interacts with SHIP2 to increase its delivery into gastric epithelial cells. Cancer Sci. 2020;111(5):1596-606. DOI: https://doi.org/10.1111/cas.14391
Ji X, Sun Z, Wu H. More powerful dysregulation of Helicobacter pylori East Asian-type CagA on intracellular signalings. BMC Microbiol. 2024;24(1):467. DOI: https://doi.org/10.1186/s12866-024-03619-4
Soutto M, Zhang X, Bhat N. Fibroblast growth factor receptor-4 mediates activation of Nuclear Factor Erythroid 2-Related Factor-2 in gastric tumorigenesis. Redox Biol. 2024;69:102998. DOI: https://doi.org/10.1016/j.redox.2023.102998
Ye Y, Bin B, Chen P. Advances in the study of the role of gastric microbiota in the progression of gastric cancer. Microb Pathog. 2025;199:107240. DOI: https://doi.org/10.1016/j.micpath.2024.107240
Salvatori S, Marafini I, Laudisi F, Monteleone G, Stolfi C. Helicobacter pylori and Gastric Cancer: Pathogenetic Mechanisms. Int J Mol Sci. 2023;24(3):87. DOI: https://doi.org/10.3390/ijms24032895
36. Noto JM, Piazuelo MB, Shah SC. Iron deficiency linked to altered bile acid metabolism promotes Helicobacter pylori-induced inflammation-driven gastric carcinogenesis. J Clin Invest. 2022;132(10):57. DOI: https://doi.org/10.1172/JCI147822
Viala J, Chaput C, Boneca IG. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nature Immunol. 2004;5(11):1166-1174. DOI: https://doi.org/10.1038/ni1131
Palrasu M, Zaika E, Paulrasu K. Helicobacter pylori pathogen inhibits cellular responses to oncogenic stress and apoptosis. PLoS Pathogens. 2022;18(6):1010628. DOI: https://doi.org/10.1371/journal.ppat.1010628
Xu Z, Li B, Du Y. Helicobacter pylori regulates ILK to influence autophagy through Rac1 and RhoA signaling pathways in gastric epithelial cells. Microbial Pathogen. 2021;158:105054. DOI: https://doi.org/10.1016/j.micpath.2021.105054
Ma JL, Zhang L, Brown LM, et al. Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. J National Cancer Institute. 2012;104(6):488-92. DOI: https://doi.org/10.1093/jnci/djs003
Li WQ, Zhang JY, Ma JL. Effects of Helicobacter pylori treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial. BMJ (Clinical research ed). 2019;366:l5016. DOI: https://doi.org/10.1136/bmj.l5016
Yan L, Chen Y, Chen F. Effect of Helicobacter pylori eradication on gastric cancer prevention: updated report from a randomized controlled trial with 26.5 Years of Follow-up. Gastroenterology. 2022;163(1):154-62. DOI: https://doi.org/10.1053/j.gastro.2022.03.039
Leung WK, Wong IOL, Cheung KS. Effects of Helicobacter pylori Treatment on Incidence of Gastric Cancer in Older Individuals. Gastroenterology. 2018;155(1):67-75. DOI: https://doi.org/10.1053/j.gastro.2018.03.028
Chiang TH, Chang WJ, Chen SL. Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and mortality: a long-term cohort study on Matsu Islands. Gut. 2021;70(2):243-50. DOI: https://doi.org/10.1136/gutjnl-2020-322200
Su XQ, Yin ZY, Jin QY. Allium vegetable intake associated with the risk of incident gastric cancer: a continuous follow-up study of a randomized intervention trial. The American journal of clinical nutrition. 2023;117(1):22-32. DOI: https://doi.org/10.1016/j.ajcnut.2022.10.017
Choi IJ, Kook MC, Kim YI. Helicobacter pylori Therapy for the Prevention of Metachronous Gastric Cancer. The New England J Med. 2018;378(12):1085-95. DOI: https://doi.org/10.1056/NEJMoa1708423
Yoo HW, Hong SJ, Kim SH. Helicobacter pylori treatment and gastric cancer risk after endoscopic resection of dysplasia: a nationwide cohort study. Gastroenterology. 2024;166(2):313-22. DOI: https://doi.org/10.1053/j.gastro.2023.10.013
Jiang X, Peng L, Zhang L. Gastric microbiota and its role in gastric carcinogenesis. Malig Spect. 2024;1(1):2-14. DOI: https://doi.org/10.1002/msp2.15
Guo Y, Zhang Y, Gerhard M. Effect of Helicobacter pylori on gastrointestinal microbiota: a population-based study in Linqu, a high-risk area of gastric cancer. Gut. 2020;69(9):1598-607. DOI: https://doi.org/10.1136/gutjnl-2019-319696
Chen L, Xu W, Lee A. The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial. EBioMedicine. 2018;35:87-96. DOI: https://doi.org/10.1016/j.ebiom.2018.08.028
Chen CC, Liou JM, Lee YC, Hong TC, El-Omar EM, Wu MS. The interplay between Helicobacter pylori and gastrointestinal microbiota. Gut microbes. 2021;13(1):1-22. DOI: https://doi.org/10.1080/19490976.2021.1909459
Jakobsson HE, Jernberg C, Andersson AF, Sjölund-Karlsson M, Jansson JK, Engstrand L. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PloS One. 2010;5(3):9836. DOI: https://doi.org/10.1371/journal.pone.0009836
He C, Peng C, Wang H. The eradication of Helicobacter pylori restores rather than disturbs the gastrointestinal microbiota in asymptomatic young adults. Helicobacter. 2019;24(4):12590. DOI: https://doi.org/10.1111/hel.12590
Martin-Nuñez GM, Cornejo-Pareja I, Clemente-Postigo M, Tinahones FJ. Gut Microbiota: The Missing Link Between Helicobacter pylori Infection and Metabolic Disorders. Front Endocrinol. 2021;12:639856. DOI: https://doi.org/10.3389/fendo.2021.639856
Peek RM, Jr., Crabtree JE. Helicobacter infection and gastric neoplasia. J Pathol. 2006;208(2):233-48. DOI: https://doi.org/10.1002/path.1868
Mauer J, Chaurasia B, Goldau J, et al. Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nature Immunol. 2014;15(5):423-30. DOI: https://doi.org/10.1038/ni.2865
Fang LJ, Lin XC, Huang DS. (1)H NMR-based metabolomics analyses in children with Helicobacter pylori infection and the alteration of serum metabolites after treatment. Microb Pathogen. 2020;147:104292. DOI: https://doi.org/10.1016/j.micpath.2020.104292
Tu Z, Wang Y, Liang J, Liu J. Helicobacter pylori-targeted AI-driven vaccines: a paradigm shift in gastric cancer prevention. Frontiers in immunology. 2024;15:1500921. DOI: https://doi.org/10.3389/fimmu.2024.1500921
Malfertheiner P, Selgrad M, Wex T. Efficacy, immunogenicity, and safety of a parenteral vaccine against Helicobacter pylori in healthy volunteers challenged with a Cag-positive strain: a randomised, placebo-controlled phase 1/2 study. Lancet Gastroenterol Hepatol. 2018;3(10):698-707. DOI: https://doi.org/10.1016/S2468-1253(18)30125-0
Zhang F, Ni L, Zhang Z. Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection. Microbial cell factories. 2024;23(1):61. DOI: https://doi.org/10.1186/s12934-024-02321-4
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