POS1033 CHILDHOOD EXPOSURES AND RISK OF RHEUMATOID ARTHRITIS IN E3N FRENCH WOMEN COHORT

Abstract

BackgroundRheumatoid arthritis (RA) results from a gene-environment interaction and is characterized by a preclinical, or asymptomatic, phase during which autoantibodies appear, in particular anti-citrullinated protein antibodies (ACPA) [1].This gene-environment interaction, occurs many years before the diagnosis of RA, possibly during childhood. Only smoking, in genetically predisposed patients (carriers of the shared HLA-DRB1 epitope), has been shown to be a reproducible risk factor for developing seropositive RA [2,3]. Other inhaled substances may play a role as many non-smokers develop RA, inducing inflammation of the lung mucosa and a systemic immune response, such as occupational exposure to silica, possibly pesticides and air pollution [4]. Early life exposures may play a major role in the pathophysiology of RA. All these elements lead us to study the impact of exposure to environmental factors in childhood on the risk of RA in adulthood, mainly airborne exposure.ObjectivesTo assess the relationships between exposure to a rural lifestyle during childhood and the risk of RA in women involved in the E3N cohort.MethodsE3N is an ongoing French prospective cohort that included 98,995 women aged 40-65 years. Women completed, every 2-3 years, mailed questionnaires on their lifestyle and health-related information. In 2002 a questionnaire on their childhood environment was assessed, including passive smoking, educational level, smoking during pregnancy and World War II deprivation scores, exposures to cats and dogs at home, whether women had lived on a farm for at least 3 successive months during childhood, and if so, the type of animals they were exposed to and their age at first pet or farm animal exposure. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident RA were estimated using multi-adjusted Cox proportional hazards regression models with age as the time scale.ResultsA total of 698 incident RA cases, among whom 77,754 non RA women were ascertained. Farming lifestyle was not associated with the risk of RA. In contrast, in a multivariable-adjusted Cox regression model including known risk factors of RA (age, active and/or passive smoking during adulthood, BMI, educational level), exposure to cats and/or dog between 1 and 2 years old was associated with a decrease risk of incident RA compared to children without pets: HR = 0.55 (95% CI 0.3-0.9), p= 0.031). Furthermore, as previously described, passive smoking in childhood [HR=1.24 (1.0-1.5) p=0.044] and high educational level ([HR=0.78 (0.6-0.9) p=0.037]; [HR=0.772 (0.6-0.9) p=0.0426] for up to 2 years and ≥3 years of university education, respectively versus no education) were shown to be associated with RA in the multi-adjusted model.ConclusionMore than farming lifestyle or the type of pet, the very early exposition to cats and/or dog (1-2 years) seems to reduce the incidence of RA while passive smoking in childhood increases it. This supports the idea that the lung and thus airborne exposures in early childhood play an important role in the genesis of RA occurring in adulthood.