Diabetes as a pan-cancer risk factor: Triangulated evidence from global burden, longitudinal cohorts, and Mendelian randomization

doi:10.4239/wjd.124123

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Publication Name

World Journal of Diabetes

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1948-9358

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Diabetes. Nov 15, 2026; 17(11): 124123
Published online Nov 15, 2026. doi: 10.4239/wjd.124123

Diabetes as a pan-cancer risk factor: Triangulated evidence from global burden, longitudinal cohorts, and Mendelian randomization

Ye Lu, Mao-Sheng Chai, Qing-Ying Lan, Qing-Mo Yang, Fu-Rong Yang, Ting-Ning Xiao, Xiao-Wen Kong, Pei-Ru Zhou, Hong Hua

Ye Lu, Mao-Sheng Chai, Qing-Ying Lan, Qing-Mo Yang, Fu-Rong Yang, Ting-Ning Xiao, Xiao-Wen Kong, Pei-Ru Zhou, Hong Hua, Department of Oral Medicine, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China

Co-corresponding authors: Pei-Ru Zhou and Hong Hua.

Author contributions: Lu Y curated the data; Lu Y, Chai MS and Lan QY edited the figure legends; Lu Y, Chai MS, Lan QY, Yang QM, Yang FR, Xiao TN and Kong XW drafted the manuscript; Lu Y, Zhou PR and Hua H prepared the tables and figures; Zhou PR and Hua H revised the manuscript, contributed equally through their joint roles in study conception, design, supervision and critical revision of the manuscript, conceived and designed the study as co-corresponding authors; all authors reviewed and approved the final version of the manuscript.

AI contribution statement: AI tools, specifically ChatGPT, were used solely for language polishing and formatting assistance. No AI tools were used to generate research data, interpret results, or formulate conclusions. All AI-assisted content was critically reviewed and revised by the authors, who take full responsibility for the accuracy, originality, and integrity of the manuscript.

Supported by the National Key Research and Development Program of China, No. 2023YFC3605603; the Program of the New Clinical Techniques of Peking University School and Hospital of Stomatology, No. PKUSSNCT-24A10; and the Beijing High-Level Innovative and Entrepreneurship Talent Support Program, Young Backbone Talent Projects, No. G202531217.

Institutional review board statement: Since the Global Burden of Disease database consists of de-identified public data, and the original studies have received ethical approval, no additional ethical review is required for our study.

Informed consent statement: National Health and Nutrition Examination Survey protocols were approved by the Centers for Disease Control and Prevention Ethics Review Board, and all participants provided informed consent.

Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.

STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.

Data sharing statement: All Global Burden of Disease data are publicly available at the https://vizhub.healthdata.org/gbd-results/. Data from National Health and Nutrition Examination Survey are available at https://wwwn.cdc.gov/nchs/nhanes/Default.aspx. The National Death Index data can be downloaded from https://www.cdc.gov/nchs/ndi. China Health and Retirement Longitudinal Study data can be accessed through http://charls.pku.edu.cn/. All datasets used in this study are publicly available and accessible for download from the respective repositories.

Corresponding author: Hong Hua, MD, PhD, Chief Physician, Professor, Department of Oral Medicine, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, No. 22 Zhongguancun South Street, Haidian District, Beijing 100081, China. honghua1968@aliyun.com

Received: June 8, 2026
Revised: July 29, 2026
Accepted: September 21, 2026
Published online: November 15, 2026
Processing time: 151 Days and 21 Hours

Abstract

BACKGROUND

Diabetes has been implicated in cancer initiation and progression; however, its contribution to cancer burden, risk, and survival remains insufficiently defined across populations, geographical regions, and analytical frameworks.

AIM

To systematically evaluate the impact of diabetes on pan-cancer and delineate shared risk patterns across malignancies.

METHODS

We integrated the Global Burden of Disease, National Health and Nutrition Examination Survey (NHANES), the National Death Index mortality data, China Health and Retirement Longitudinal Study, and genome-wide association study datasets. The Global Burden of Disease estimates were used to assess temporal trends. Multivariable logistic regression was used to examine associations between diabetes and cancer prevalence; Kaplan-Meier, Cox proportional hazards, and competing risk analyses were used to evaluate survival outcomes; and Mendelian randomization was used to assess genetic evidence for causality.

RESULTS

The cancer burden attributable to high fasting plasma glucose levels increased steadily from 1990 to 2021. After multivariable adjustment, diabetes was independently associated with higher cancer prevalence in NHANES (odds ratio = 1.64, 95%CI: 1.18-2.28) and China Health and Retirement Longitudinal Study cohort (odds ratio = 2.00, 95%CI: 1.11-3.59), and with poorer survival (hazard ratio = 1.25, 95%CI: 1.03-1.51) in NHANES. Participants with diabetes generally exhibit higher cancer-specific mortality rates. Mendelian randomization further supported a causal association between diabetes and overall cancer risk, while established diabetes-related markers showed dose-response associations with cancer prevalence.

CONCLUSION

These findings identify diabetes as a systemic pan-cancer risk factor associated with increase cancer burden, elevated cancer risk, and poor survival outcomes.

Keywords: Diabetes; Hyperglycemia; Pan-cancer; Cancer burden; Cancer-specific mortality; Risk stratification

Core Tip: Using multiple independent datasets and Mendelian randomization, this study links diabetes to a rising pan-cancer burden, higher cancer prevalence and poorer survival. Longer diabetes duration and higher insulin-resistance markers showed dose-response associations with cancer prevalence, identifying diabetes-related indicators as quantifiable markers of cancer risk. These findings support diabetes-informed cancer risk stratification, targeted prevention and longitudinal surveillance in high-risk populations.