Benzo[a]pyrene exposure and incident risks of digestive system cancers: Insights from nested case-control studies and adverse outcome pathway network analysis

• Published in: Journal of hazardous materials Vol. 487; p. 137159
• Main Authors: Zhao, Hui, Xiao, Yang, Fu, Ye, Guan, Xin, Fu, Ming, Wang, Chenming, Zhou, Yuhan, Hong, Shiru, You, Yingqian, Wang, Yuxi, Chen, Shengli, Zhang, Yichi, Bai, Yansen, Guo, Huan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.04.2025
• Subjects: Adult; Adverse outcome pathway; Adverse Outcome Pathways; Aged; apoptosis; Benzo(a)pyrene - toxicity; Benzo[a]pyrene; carcinogenesis; carcinogenicity; carcinogens; Carcinogens - toxicity; Case-Control Studies; cell proliferation; digestive system; Digestive system cancer; Digestive System Neoplasms - chemically induced; Digestive System Neoplasms - epidemiology; Female; Humans; lung neoplasms; Male; Middle Aged; Nested case-control study; Benzo[a]pyrene; Digestive system cancer; Nested case-control study; Adverse outcome pathway
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2025.137159

Benzo[a]pyrene (B[a]P) is a recognized carcinogen for lung cancer, but its associations with digestive system cancers (DSCs) remain unclear and the common carcinogenic mechanisms are not fully understood. We conducted five nested case-control studies within the Dongfeng-Tongji cohort, including esophageal (EC, n = 58), gastric (GC, n = 103), colorectal (CRC, n = 220), hepatic (HC, n = 117), and pancreatic cancers (PC, n = 45). For each case, two sex and age ( ± 5 years) matched healthy controls were selected. We observed significant J-shaped associations between plasma concentrations of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) adducts and five DSCs (all P for non-linear <0.05). The subjects with high BPDE-Alb exposure exhibited a separate 2.19, 2.14, 1.67, 2.40, and 1.78-fold incident risks of EC, GC, CRC, HC, and PC (95% CI: 1.00–4.83, 1.24–3.67, 1.15–2.43, 1.48–3.90, and 0.71–4.47, respectively) than those with low exposure. Furthermore, the adverse outcome pathway (AOP) network indicated five molecular initiation events and 18 subsequent key events, particularly, the alterations in receptors of AhR, EGFR accompanied by regulations of cell proliferation and apoptosis pathways (e.g., PI3K-Akt, TNF signaling) may facilitate common carcinogenic processes. Our findings revealed the positive associations of B[a]P exposure with five DSCs, and the dysregulation of proliferation and apoptosis may initiate B[a]P-induced cancer development. [Display omitted] •There were non-linear J-shaped associations of B[a]P with five DSCs incident risks.•High levels of B[a]P were associated with elevated incident risks of EC, GC, CRC and HC.•Perturbations of five MIEs and 18 KEs may underly B[a]P-induced carcinogenesis.