Influence of occupational exposure to endocrine disrupting chemicals on sex-hormone levels.
Background: There are sex-specific differences in the incidence, morbidity and mortality of various cancers. However, the determinants of these disparities are still not understood. Sex hormones, an obvious difference between men and women, have been shown to affect the development of various cancers. Endocrine disrupting chemicals (EDCs) are chemicals that interferes with the proper functioning of sex hormones. We are exposed to these chemicals in the environment and in diet; however, workers in certain sectors are highly exposed to EDCs. The proposed research aims to evaluate the association between occupational exposures to EDCs and sex hormones levels in the UK Biobank.
Methods: A cross-sectional analysis will be nested within the UK Biobank (proposed duration: 2 years). All participants who provided information on their current employment and have measured sex hormone levels (i.e., serum estradiol, testosterone and sex hormone-binding globulin (SHBG)) will be included. Occupational exposure to EDC will be estimated using two job exposure matrices (JEMs): EDC-JEM and CANJEM. The EDC-JEM is proposed as the primary exposure assessment tool and will be used to estimate the exposure for seven groups of substances according to three levels of exposure ("unlikely ever-exposed," "possibly ever-exposed" or "probably ever-exposed"). Using CANJEM, 20 EDCs will be considered; three exposure metrics will be defined including ever, average and cumulative exposure to any of the 20 EDCs of interest.
Multivariable linear regression will be used to assess the association between lifetime occupational EDC exposure and sex hormone levels in separate models while adjusting for potential confounders, in the total study population and separately among men and women. Potential effect modification by sex will be tested via the inclusion of cross products in the models.
Impact: This proposed project is funded as a part of a Chair in Sex and Gender Science in Cancer Research funded by the Canadian Institutes of Health Research. The overall aim of this Chair is to elucidate the role of EDCs in cancer etiology. Currently, using data from the Canadian Partnership for Tomorrow's Health, we are examining the role of occupational exposure to EDCs in colorectal, lung, breast and prostate cancer etiology. Complementary to this work, the proposed research in the UK Biobank will inform on the mechanism in which EDCs may affect cancer risk i.e., via the modification of sex hormone levels and thus, strengthen the evidence in elucidating the role of EDCs in cancer etiology.