Background/Purpose: Silica exposure has been associated with an increased risk of developing ACPA+ (anti-citrullinated protein antibody) RA, especially among smokers (1). These findings were based on a Caucasian population. In this study we aimed at examining the association between silica exposure (and its interaction with smoking) and the risk of ACPA+ RA in an Asian population. In addition, we examined possible interaction between silica exposure and the major genetic risk factor for ACPA+ RA, i.e. the HLA-DRB1 shared epitope (SE) alleles, in both a Caucasian and an Asian population.

Methods: Data from the Malaysian EIRA (MyEIRA) and its sister study, the Swedish EIRA study were used. In total, 149 incident cases and 213 controls from MyEIRA  and 823 incident cases and 1161 controls from EIRA, all men, were included. Self-reported silica exposure, defined as exposure to stone dust, rock drilling or stone crushing were taken into consideration. Smoking was defined as ever/never cigarette smokers. We examined the association between exposure to silica with the risk of ACPA+ RA, by calculating odds ratios (OR) with 95% confidence intervals (CI), using logistic regression. All analyses were adjusted for age and residential place. Interaction was evaluated by calculating the attributable proportion (AP) due to interaction and its 95% confidence interval (CI).

Results: In MyEIRA, an increased risk of ACPA+ RA (OR=2.88, 95%CI 1.02-8.14) was observed among those exposed to silica. Ever smokers exposed to silica had a particularly high risk of ACPA+ RA (OR= 8.27, 95%CI 1.64-41.44), compared with never smokers not exposed to silica. No association was found regarding ACPA- RA. When data from both studies were combined, we found that silica-exposed individuals with SE alleles had almost eleven times higher risk of ACPA+RA however the interaction was insignificant (AP=0.27, 95%CI -0.09-0.64).

Conclusion: Silica exposure in combination with smoking among men increased the risk of ACPA+ RA in an Asian population. These data extend previous results based on a Caucasian population reported from the Swedish EIRA study (1). In the combined analyses of these studies, there was an indication of interaction between silica and SE, though it was insignificant. We believe that this finding strengthen the hypothesis of modifiable lung exposure and risk for ACPA+ RA.

Reference:

1. Patrik et al., Silica exposure among male current smokers is associated with a high risk of developing ACPA-positive rheumatoid arthritis. Ann Rheum Dis, 2010. 69: p.1072-1076.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-association-between-silica-and-the-risk-of-anti-citrullinated-protein-antibody-positive-ra-in-the-malaysian-and-swedish-epidemiological-investigation-of-rheumatoid-arthritis-studies/