Abstract

BackgroundRheumatoid arthritis (RA) is an inflammatory rheumatic disease of multifactorial aetiology, which preferentially affects women. To date, active personal smoking has been the most reproducibly reported risk factor for anti-citrullinated protein antibodies (ACPA) positive RA. Fish consumption has been thought to reduce the risk of rheumatoid arthritis (RA), but reported data were conflicting.ObjectivesTo assess the association between fish consumption (overall, lean fish, and oily fish) and the risk of RA.MethodsThe E3N study (Etude Epidémiologique auprès des femmes de la Mutuelle générale de l’Education Nationale) is a French prospective cohort investigating environmental factors associated with chronic diseases. It follows 98,995 healthy French women since 1990 covered by a national health insurance primarily involving teachers. RA cases have been previously identified with specific questionnaires and medication reimbursement database. Dietary data were collected via a validated food-frequency questionnaire in 1993. Cox proportional hazards models were used to calculate HRs and 95% CIs for incident RA depending on the tertiles of consumption of overall, lean and oily fish. Models were adjusted for age and for the main potential confounders. Stratified analyses were conducted depending on the active smoking status (never or ever-smoker).ResultsAmong 62,629 women, 480 incident cases of RA were identified. In the overall population, we did not find a linear association between overall fish consumption and RA risk (p for trend 0.65), but a moderate consumption of fish (16.7−31.1 g/day, roughly corresponding to 1 to 2 servings a week) was associated with a decreased risk of RA (HR 0.74; 95% CI 0.59—0.94 for tertile 2 compared with tertile 1), especially among ever smoking women (HR 0.61; 95% CI 0.44—0.85). Although not statistically significant, a trend towards an inverse association was only found with oily fish consumption (HR 0.81; 95% CI 0.65—1.02 for tertile 2), but not with lean fish.ConclusionIn our large population-based cohort study of French women, there was a U-shaped relationship between overall fish consumption and the risk of RA, with a reduced RA risk only in moderate consumers. The inverse association was restricted to ever-smokers. When separately considering oily and lean fish, the second tertile of oily fish consumption was inversely associated with the risk of RA only in never-smokers, while there was no association with lean fish.Table 1.Hazard ratios (95% confidence intervals) for the risk of rheumatoid arthritis (RA) by tertiles of fish consumption (N = 62,629)Fish consumptionNon-cases N (%)RA N (%)Model 1 HR (95% CI)Model 2 HR (95% CI)All populationN=62,149N=480 Tertile 1 (0−16.7 g/day)20,509 (33.00)172 (35.83)ReferenceReference Tertile 2 (16.7−31.1 g/day)19,628 (31.58)121 (25.21)0.74 [0.58; 0.93]0.74 [0.59; 0.94] Tertile 3 (31.1−261 g/day)22,012 (35.42)187 (38.96)0.99 [0.80; 1.22]0.99 [0.80; 1.22] Ptrend0.630.65Never smokersN=33,314N=244 Tertile 1 (0−16.7 g/day)11,322 (33.99)79 (32.38)ReferenceReference Tertile 2 (16.7−31.1 g/day)10,556 (31.69)66 (27.05)0.89 [0.64; 1.24]0.90 [0.65; 1.25] Tertile 3 (31.1−261 g/day)11,436 (34.33)99 (40.57)1.19 [0.88; 1.60]1.21 [0.90; 1.64] Ptrend0.150.12Ever smokersN=28,835N=236 Tertile 1 (0−16.7 g/day)9,187 (31.86)93 (39.41)ReferenceReference Tertile 2 (16.7−31.1 g/day)9,072 (31.46)55 (23.31)0.60 [0.43; 0.84]0.61 [0.44;0.85] Tertile 3 (31.1−261 g/day)10,576 (36.68)88 (37.29)0.81 [0.60; 1.09]0.81 [0.60; 1.08] Ptrend0.390.36M1: Adjusted for total daily intake and ageM2: M1+ body mass index (kg/m2), smoking status (current smoker, non-smoker, former smoker, except for stratified analyses), passive smoking in childhood (no, yes), gastrointestinal transit (normal, diarrhoea, constipation, alternating diarrhoea/constipation), educational level (< High School, up to 2-level university, 3-4 level university), and physical activity (in quartiles)Disclosure of InterestsNone declared

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