American Association for Cancer Research
epi-23-0828_supplementary_figure_s3_supps3f.pdf (73.75 kB)

Supplementary Figure S3 from The Influence of Smoking and Occupational Risk Factors on DNA Methylation in the AHRR and F2RL3 Genes

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posted on 2024-02-06, 08:21 authored by Laura Pelland-St-Pierre, Michael C. Pham, Alice Quynh Huong Nguyen, Romain Pasquet, Sherryl A. Taylor, Delphine Bosson-Rieutort, Anita Koushik, Vikki Ho

Supplementary Figure S3 shows, for each graph, the effect estimate and the 95% CI plotted across all 33 CpG sites in the AHRR gene. Multivariable models included adjustment for age, phase of blood sampling, education level, ethnicity, and smoking (CSI - cumulative smoking index). The interpretation of the effect estimate is the difference in mean methylation level relative to those never exposed to each agent (reference group). Categorization of occupational exposures was based on the FWI as never exposed (FWI=0, reference group), Low exposure (>0 and lower than the population median, in blue square) and High exposure (≥population median, in red triangle). * Denotes a p-value < 0.05.


Canadian Institutes of Health Research (IRSC)



AHRR and F2RL3 hypomethylation has been associated with lung cancer. In this study, we investigated the cross-sectional association between smoking and occupational exposures, and AHRR and F2RL3 methylation. A case–control study was nested in CARTaGENE to examine the association between AHRR and F2RL3 methylation and lung cancer risk (200 cases; 400 controls). A secondary analysis was conducted using the data collected from this nested study; namely, baseline information on participants’ smoking behavior and longest-held job was obtained. A cumulative smoking index summarized information on the number of cigarettes smoked, duration of smoking, and time since cessation. Exposure to 13 occupational agents was estimated using the Canadian Job Exposure Matrix. In baseline blood samples, methylation ratios of 40 CpG sites in the AHRR and F2RL3 genes were measured using Sequenom EpiTYPER. Separate least squares regression models were used to estimate the associations between smoking and occupational exposures, and average AHRR and F2RL3 methylation levels, while adjusting for confounders identified from directed acyclic graphs. In both genes, smoking was associated with lower average methylation levels. Occupational exposure to aromatic amines, cadmium, and formaldehyde were associated with lower AHRR methylation while, only benzene was associated with F2RL3 hypomethylation; these associations were stronger among ever smokers. Our findings support that smoking and occupational exposures to some agents are associated with AHRR and F2RL3 hypomethylation. Our results inform on mechanisms underlying environmental exposures in lung cancer etiology; future studies should prioritize studying joint exposures.

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