Epigenome-wide DNA methylation signature of benzo[a]pyrene exposure and their mediation roles in benzo[a]pyrene-associated lung cancer development

Benzo[a]pyrene (B[a]P) is a typical carcinogen associated with increased lung cancer risk, but the underlying mechanisms remain unclear. This study aimed to investigate epigenome-wide DNA methylation associated with B[a]P exposure and their mediation effects on B[a]P-lung cancer association in two lung cancer case-control studies of 462 subjects. Their plasma levels of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) adducts and genome-wide DNA methylations were separately detected in peripheral blood by using enzyme-linked immunosorbent assay (ELISA) and genome-wide methylation arrays. The epigenome-wide meta-analysis was performed to analyze the associations between BPDE-Alb adducts and DNA methylations. Mediation analysis was applied to assess effect of DNA methylation on the B[a]P-lung cancer association. We identified 15 CpGs associated with BPDE-Alb adducts (P−meta