IPF risk: two's company, three's a crowd? Asbestos exposure, cigarette smoke, and MUC5B promoter polymorphism rs35705950. Findings from the idiopathic pulmonary fibrosis job exposures study (IPFJES)

Background: We hypothesised that a proportion of cases of Idiopathic Pulmonary Fibrosis (IPF) are due to occult occupational asbestos exposure. Aims and Objectives: To investigate the relationship between occupational asbestos exposure, cigarette smoking, and MUC5B rs35705950 genotype with respect to IPF risk. Methods: Asbestos exposure for 960 participants (494 cases, 466 controls) was assessed using a job exposure matrix (JEM) based on occupational proportional mortality data for pleural mesothelioma and by means of a validated asbestos exposure reconstruction method in a UK multicentre hospital-based case-control study, IPFJES. Results: Table 1: Logistic regression of ever smoking and ever being occupationally asbestos exposed (inferred by job title) stratified by MUC5B rs35705950 genotype. Ever being occupationally asbestos exposed was defined as ever having a job that was medium or high risk for asbestos exposure. 1additive model, adjusted for age and smoking. 2analysis limited to genotyped participants (N=818). 3Genotype of MUC5B rs35705950, T is minor allele. Neither smoking or asbestos exposure were significant alone. Conclusion: In the aetiology of IPF there appears to be an interaction between occupational exposure to asbestos, smoking, and the minor allele of the MUC5B promoter variant rs35705950.