Chang H, Perez-Losada J, Mao JH. Emerging multifaceted roles of the microbiome in cancer susceptibility. World J Clin Oncol 2025; 16(9): 111379 [PMID: 41024841 DOI: 10.5306/wjco.v16.i9.111379]
Corresponding Author of This Article
Jian-Hua Mao, Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, United States. jhmao@lbl.gov
Research Domain of This Article
Oncology
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 Clin Oncol. Sep 24, 2025; 16(9): 111379 Published online Sep 24, 2025. doi: 10.5306/wjco.v16.i9.111379
Emerging multifaceted roles of the microbiome in cancer susceptibility
Hang Chang, Jesus Perez-Losada, Jian-Hua Mao
Hang Chang, Jian-Hua Mao, Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States
Jesus Perez-Losada, Instituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Universidad de Salamanca, Salamanca 37007, Spain
Jesus Perez-Losada, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca 37007, Spain
Author contributions: Mao JH planned the outline of the manuscript; Chang H, Perez-Losada J and Mao JH wrote and edited the manuscript; all authors have read and approved the final manuscript.
Supported by The United States Department of Defense Breast Cancer Research Program, No. BC190820; and the National Institutes of Health, No. R01ES031322.
Conflict-of-interest statement: The authors declare no competing interests.
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: Jian-Hua Mao, Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, United States. jhmao@lbl.gov
Received: June 30, 2025 Revised: July 14, 2025 Accepted: August 21, 2025 Published online: September 24, 2025 Processing time: 87 Days and 11.9 Hours
Abstract
Identifying the factors that contribute to individual susceptibility to cancer is essential for both prevention and treatment. The advancement of biotechnologies, particularly next-generation sequencing, has accelerated the discovery of genetic variants linked to cancer susceptibility. While hundreds of cancer-susceptibility genes have been identified, they only explain a small fraction of the overall cancer risk, a phenomenon known as "missing heritability". Despite progress, even considering factors such as epistasis, epigenetics, and gene-environment interactions, the missing heritability remains unresolved. Recent research has revealed that an individual's microbiome composition plays a significant role in cancer susceptibility through several mechanisms, such as modulating immune cell activity and influencing the presence or removal of environmental carcinogens. In this review, we examine the multifaceted roles of the microbiome in cancer risk and explore gene-microbiome and environment-microbiome interactions that may contribute to cancer susceptibility. Additionally, we highlight the importance of experimental models, such as collaborative cross mice, and advanced analytical tools, like artificial intelligence, in identifying microbial factors associated with cancer risk. Understanding these microbial determinants can open new avenues for interventions aimed at reducing cancer risk and guide the development of more effective cancer treatments.
Core Tip: Understanding individual susceptibility to cancer is critical for effective prevention and treatment strategies. While genetic studies have identified numerous cancer-susceptibility genes, much of the heritable risk remains unexplained. Emerging evidence indicates the microbiome as a key contributor to this "missing heritability". Microbiomes influence cancer risk through immune modulation, metabolic activity, and interaction with environmental exposures. This review discusses the complex gene-microbiome-environment interplay in cancer susceptibility and emphasizes the value of integrative models and tools, such as collaborative cross mice and artificial intelligence, for uncovering microbial determinants of cancer risk.
