期刊
JOURNAL OF HAZARDOUS MATERIALS
卷 416, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jhazmat.2021.125839
关键词
Benzo[a]pyrene; Plasma BPDE-Alb adducts; DNA methylation; Lung cancer; Mediation effect
资金
- National Natural Science Foundation of China [82073650, 81773398, 81722038]
- National Youth Top Talent Support Program
This study identified 15 CpG sites associated with BPDE-Alb adducts, with methylation levels at 5 sites mediating the association between BPDE-Alb adducts and lung cancer risk. The addition of these CpG sites improved the discrimination for lung cancer compared to traditional factors. These results highlight DNA methylation alterations as potential mediators in lung tumorigenesis induced by B[a]P exposure.
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 < 1.0 x 10-5), among which the methylation levels at five loci (cg06245338, cg24256211, cg15107887, cg02211741, and cg04354393 annotated to UBE2O, SAMD4A, ACBD6, DGKZ, and SLFN13, respectively) mediated a separate 38.5%, 29.2%, 41.5%, 47.7%, 56.5%, and a joint 58.2% of the association between BPDE-Alb adducts and lung cancer risk. Compared to the traditional factors [area under the curve (AUC) = 0.788], addition of these CpGs exerted improved discriminations for lung cancer, with AUC ranging 0.828-0.861. Our results highlight DNA methylation alterations as potential mediators in lung tumorigenesis induced by B[a]P exposure.
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