Raza Y, Mubarak M, Memon MY, Alsulaimi MS. Update on molecular pathogenesis of Helicobacter pylori-induced gastric cancer. World J Gastrointest Pathophysiol 2025; 16(2): 107052 [DOI: 10.4291/wjgp.v16.i2.107052]
Corresponding Author of This Article
Muhammed Mubarak, Professor, Department of Histopathology, Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi 74200, Sindh, Pakistan. drmubaraksiut@yahoo.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Pathophysiol. Jun 22, 2025; 16(2): 107052 Published online Jun 22, 2025. doi: 10.4291/wjgp.v16.i2.107052
Update on molecular pathogenesis of Helicobacter pylori-induced gastric cancer
Yasir Raza, Muhammed Mubarak, Muhammad Yousuf Memon, Mohammed Saud Alsulaimi
Yasir Raza, Department of Microbiology, University of Karachi, Karachi 75270, Sindh, Pakistan
Muhammed Mubarak, Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
Muhammad Yousuf Memon, Mohammed Saud Alsulaimi, Department of Gastroenterology, King Saud Hospital, Unaizah, Unaizah 56437, Al Qassim, Saudi Arabia
Author contributions: Raza Y, Mubarak M, and Memon YM contributed equally to the conception and study design; Raza Y, Mubarak M, and Memon YM performed relevant research and participated in primary and final drafting; Mubarak M and Alsulaimi MS critically reviewed and approved the final manuscript.
Conflict-of-interest statement: All authors have declared that no conflict of interest exists with regard to this work.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Muhammed Mubarak, Professor, Department of Histopathology, Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi 74200, Sindh, Pakistan. drmubaraksiut@yahoo.com
Received: March 14, 2025 Revised: April 9, 2025 Accepted: April 21, 2025 Published online: June 22, 2025 Processing time: 97 Days and 17.8 Hours
Abstract
Helicobacter pylori (H. pylori) infection is one of the most prevalent bacterial infections affecting mankind. About half of the world’s population is infected with it. It causes several upper gastrointestinal diseases, including gastric cancer (GC). It has been identified as a major risk factor for GC. GC is one of the most common cancers affecting humans and the third leading cause of cancer-related deaths worldwide. H. pylori infection causes an inflammatory response that progresses through a series of intermediary stages of precancerous lesions (gastritis, atrophy, intestinal metaplasia, and dysplasia) to the final development of GC. Among infected individuals, approximately 10% develop severe gastric lesions such as peptic ulcer disease, 1%-3% progress to GC, and 0.1% develop mucosa-associated lymphoid tissue followed by the development of lymphoma. The bacterium has many virulence factors, including cytotoxin-associated gene A, vacuolating cytotoxin A, and the different outer membrane proteins that cause cancer by different mechanisms. These virulence factors activate cell signaling pathways such as PI3-kinase/Akt, JAK/STAT, Ras, Raf, and ERK signaling that control cell proliferation. Uncontrolled proliferation can lead to cancer. In addition, the repair of DNA damage may also be impaired by H. pylori infection. Reduced DNA repair in combination with increased DNA damage can result in carcinogenic mutations. The accurate identification of pathogenetic pathways is imperative for the development of targeted diagnostic markers and personalized treatments. This scoping review aims to update the readers on the role of H. pylori in the development of GC. It will focus on the molecular mechanisms underpinning gastric carcinogenesis in H. pylori infection. It will highlight the interaction between bacterial virulence factors and host cellular pathways, providing insights into potential therapeutic targets and preventive strategies.
Core Tip: Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer (GC), the third leading cause of cancer-related deaths. H. pylori triggers chronic inflammation, progressing through precancerous stages (gastritis, atrophy, intestinal metaplasia, dysplasia) to GC. Virulence factors like cytotoxin-associated gene A and vacuolating cytotoxin A activate oncogenic signaling pathways (PI3K/Akt, JAK/STAT, Ras/Raf/ERK), promoting uncontrolled cell proliferation and impairing DNA repair, leading to carcinogenic mutations. While 1%-3% of infected individuals develop GC, understanding these molecular mechanisms is crucial for identifying diagnostic markers and developing targeted therapies. This review explores H. pylori's role in gastric carcinogenesis, emphasizing bacterial-host interactions and potential preventive strategies.
