Ecotoxicology and Environmental Safety (Feb 2024)

Mediation of association between benzo[a]pyrene exposure and lung cancer risk by plasma microRNAs: A Chinese case-control study

  • Yang Xiao,
  • Chenliang Liu,
  • Ye Fu,
  • Guorong Zhong,
  • Xin Guan,
  • Wending Li,
  • Chenming Wang,
  • Shiru Hong,
  • Ming Fu,
  • Yuhan Zhou,
  • Yingqian You,
  • Tianhao Wu,
  • Xiaomin Zhang,
  • Meian He,
  • Yangkai Li,
  • Huan Guo

Journal volume & issue
Vol. 271
p. 115980

Abstract

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Epidemiologic studies have reported the positive relationship of benzo[a]pyrene (BaP) exposure with the risk of lung cancer. However, the mechanisms underlying the relationship is still unclear. Plasma microRNA (miRNA) is a typical epigenetic biomarker that was linked to environment exposure and lung cancer development. We aimed to reveal the mediation effect of plasma miRNAs on BaP-related lung cancer. We designed a lung cancer case-control study including 136 lung cancer patients and 136 controls, and measured the adducts of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) and sequenced miRNA profiles in plasma. The relationships between BPDE-Alb adducts, normalized miRNA levels and the risk of lung cancer were assessed by linear regression models. The mediation effects of miRNAs on BaP-related lung cancer were investigated. A total of 190 plasma miRNAs were significantly related to lung cancer status at Bonferroni adjusted P 2 between plasma samples before and after tumor resection surgery at Bonferroni adjusted P < 0.05. Especially, among the 57 lung cancer-associated miRNAs, BPDE-Alb adducts were significantly related to miR-17–3p, miR-20a-3p, miR-135a-5p, miR-374a-5p, miR-374b-5p, miR-423–5p and miR-664a-5p, which could in turn mediate a separate 42.2%, 33.0%, 57.5%, 36.4%, 48.8%, 32.5% and 38.2% of the relationship of BPDE-Alb adducts with the risk of lung cancer. Our results provide non-invasion biomarker candidates for lung cancer, and highlight miRNAs dysregulation as a potential intermediate mechanism by which BaP exposure lead to lung tumorigenesis.

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