Long-term exposure to ambient benzene and incident type 2 diabetes mellitus in a national cohort: The modifying effect of genetic susceptibility

Zhi-Hao Xiao; Qian Li; Xinwei Guo; Guangfeng Long; Zitong Meng; Cheng Xu

doi:10.1016/j.envres.2025.122197

Long-term exposure to ambient benzene and incident type 2 diabetes mellitus in a national cohort: The modifying effect of genetic susceptibility

Environ Res. 2025 Jun 19:284:122197. doi: 10.1016/j.envres.2025.122197. Online ahead of print.

Authors

Zhi-Hao Xiao¹, Qian Li¹, Xinwei Guo², Guangfeng Long³, Zitong Meng⁴, Cheng Xu⁵

Affiliations

¹ School of Public Health, Nanjing Medical University, Nanjing, 210000, China.
² School of Public Health, Guangxi Medical University, Nanning, 530021, China.
³ Department of Clinical Laboratory, Children's Hospital of Nanjing Medical University, Guangzhou Road #72, Nanjing, 210008, China.
⁴ Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China. Electronic address: mzt19951103@163.com.
⁵ Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China; Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention, No.6 Shuangyong Road, Nanning, 530021, Guangxi, China; Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, No.6 Shuangyong Road, Nanning, 530021, Guangxi, China. Electronic address: chengxunjmu@163.com.

PMID: 40541909
DOI: 10.1016/j.envres.2025.122197

Abstract

Background: Epidemiological evidence on the link between long-term ambient benzene exposure and type 2 diabetes mellitus (T2DM) risk is insufficient.

Methods: We analyzed 329,210 participants from the UK Biobank (2006-2010) using spatiotemporal modeling to evaluate benzene concentrations. We employed Cox proportional hazards models to explore the relationship between benzene exposure and T2DM onset. Causal relationships were examined using negative control outcomes. Moreover, we assessed interaction effects using relative excess risk due to interaction (RERI) and attributable proportion (AP) to understand genetic susceptibility's role in benzene exposure-related T2DM risk.

Results: Over a median 11.8-year follow-up, 11,552 T2DM cases were recorded. The Cox model revealed a hazard ratio of 1.30 (95 % CI: 1.27, 1.33) per IQR (interquartile range) increase in benzene. Genetic factors significantly modified impact of benzene on T2DM risk, with those high genetically predisposed and the highest benzene exposure showing the highest risk and calculated RERI and AP were 1.23 and 0.20, respectively.

Conclusion: Our study evidences a causal link between benzene exposure and increased T2DM risk, exacerbated by genetic susceptibility. These insights suggest that reducing air pollution might mitigate T2DM development.

Keywords: Additive interaction; Ambient benzene; Genetic predisposition; Type 2 diabetes mellitus; UK biobank.