8291448 Association between occupational agricultural exposures and epigenetic modifications in DNA from granulocytes in a French agricultural worker population

<h3>Objective</h3> Occupational agricultural exposures have already been associated with numerous diseases in epidemiological studies involving large cohorts. More precisely, cancers such as prostate cancer and non-Hodgkin lymphomas are strongly linked to pesticides use, particularly in agricultural environments. However, although these exposures have been studied epidemiologically, the biological plausibility of the link between such exposures and cancer development has not been firmly established. One of the mechanisms proposed by the French national institute of health and medical research to explain cancer onset associated with occupational agricultural exposures involves epigenetic modifications. These modifications are also usually associated with other diseases and are known to be influenced by environmental exposures. The objective of this project was therefore to investigate the biological plausibility of the association between occupational agricultural exposures and cancer onset by evaluating the effect of these exposures on epigenetic modifications of DNA derived from granulocytes. <h3>Material and Methods</h3> A quantification method for 5-methylcytidine (5mC) and 5-hydroxymethylcytidine (5hmC) by liquid chromatography coupled with tandem mass spectrometry was developed. This method allows the quantification of global scale DNA methylation and hydroxymethylation by quantifying 5-methyl-cytidine and 5-hydroxymethyl-cytidine. It was then applied to 539 samples from a French agricultural biobank. Accompanying questionnaires provided information on health determinants, psychosocial parameters, and agricultural exposures for each individual. Univariate analyses were performed on each parameter, followed by the construction of multivariate models. <h3>Results</h3> These models revealed the impact of various exposures on DNA methylation. Health determinants, psychosocial parameters and agricultural exposures both showed an impact on DNA global methylation. Concerning agricultural activities, pesticide use, agricultural equipment maintenance, milking, rodenticide use, and hormone use were shown affect global epigenetic modifications in individuals within the final multivariate models. <h3>Conclusion</h3> The highlighted occupational agricultural tasks were associated with an increased cancer risk in epidemiological studies, particularly AGRICAN.