Reproductive factors, hormone use, and endocrine disruptors in the etiology of lymphoid neoplasms = Factors reproductius, ús d’hormones i disruptors endocrins en l’etiologia de les neoplàsies limfoides

Abstract

Lymphoid neoplasms are a heterogeneous group of cancers characterized by the neoplastic or clonal proliferation of lymphoid cells in different stages of differentiation. The incidence rate of these neoplasms has seen a rise in some western countries since the 1970s and it seems to have reached a plateau during the last decade. Incidence rates are higher in men than in women for most lymphoma subtypes; however, the causes explaining these differences by sex are unknown. We hypothetised that hormonal factors could have a role in lymphoma etiology.

The general aim of this thesis was to assess the risk of lymphoid neoplasms in relation to reproductive factors and occupational exposure to endocrine disruptors. We used different studies and populations to evaluate our hypothesis: the EpiLymph study, the InterLymph consortium, the International Multiple Myeloma Consortium, and a systematic review. As well, we developed a new tool to estimate occupational exposures to a specific type of endocrine disruptors.

We observed contradictory findings across studies and lymphoma subtypes concerning the association between lymphoma and parity, as well as hormonal contraceptives. We observed inverse associations between postmenopausal hormone therapy and lymphoma, although we noticed in our systematic review that cohort studies usually found null associations. We observed associations with lymphoma and prolonged (≥30 years) occupational exposure to endocrine disrupting chemicals, in particular for multiple myeloma and chronic lymphocytic leukemia. Associations were observed between lymphoma and prolonged occupational exposures to organic solvents, pesticides, brominated flame retardants, alkylphenolic compounds, and metals. To further explore the associations with alkylphenolic compounds, we developed a job-exposure matrix on these compounds considering relevant changes in use over time.

In conclusion, our results indicate that reproductive factors and exogenous hormone use are unlikely to play a role in lymphomagenesis. The associations between occupational exposure to endocrine disrupting chemicals and lymphoma need to be further explored in studies using a more detailed exposure assessment.