TY - JOUR
T1 - What role for asbestos in idiopathic pulmonary fibrosis?
T2 - Findings from the IPF job exposures case-control study
AU - Reynolds, Carl J.
AU - Sisodia, Rupa
AU - Barber, Chris
AU - Moffatt, Miriam
AU - Minelli, Cosetta
AU - De Matteis, Sara
AU - Cherrie, John W.
AU - Newman Taylor, Anthony
AU - Cullinan, Paul
N1 - © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/2
Y1 - 2023/2
N2 - BACKGROUND: Asbestos has been hypothesised as the cause of the recent global increase in the incidence of 'idiopathic' pulmonary fibrosis (IPF). Establishing this has important diagnostic and therapeutic implications. The association between occupational asbestos exposure and IPF, and interaction with a common (minor allele frequency of 9% in European populations) genetic variant associated with IPF,
MUC5B rs35705950, is unknown.
METHODS: Multicentre, incident case-control study. Cases (n=494) were men diagnosed with IPF at 21 UK hospitals. Controls (n=466) were age-matched men who attended a hospital clinic in the same period. Asbestos exposure was assessed at interview using a validated job exposure matrix and a source-receptor model. The primary outcome was the association between asbestos exposure and IPF, estimated using logistic regression adjusted for age, smoking and centre. Interaction with
MUC5B rs35705950 was investigated using a genetic dominant model.
RESULTS: 327 (66%) cases and 293 (63%) controls ever had a high or medium asbestos exposure risk job; 8% of both cases and controls had cumulative exposure estimates ≥25 fibre ml⁻¹ years. Occupational asbestos exposure was not associated with IPF, adjusted OR 1.1 (95% CI 0.8 to 1.4; p=0.6) and there was no gene-environment interaction (p=0.3). Ever smoking was associated with IPF, OR 1.4 (95% CI 1 to 1.9; p=0.04) and interacted with occupational asbestos exposure, OR 1.9 (95% CI 1 to 3.6; p=0.04). In a further non-specified analysis, when stratifying for genotype there was significant interaction between smoking and work in an exposed job (p<0.01) for carriers of the minor allele of
MUC5B rs35705950.
CONCLUSION: Occupational asbestos exposure alone, or through interaction with
MUC5B rs35705950 genotype, was not associated with IPF. Exposure to asbestos and smoking interact to increase IPF risk in carriers of a common genetic variant, the minor allele of
MUC5B rs35705950.
TRIAL REGISTRATION NUMBER: NCT03211507.
AB - BACKGROUND: Asbestos has been hypothesised as the cause of the recent global increase in the incidence of 'idiopathic' pulmonary fibrosis (IPF). Establishing this has important diagnostic and therapeutic implications. The association between occupational asbestos exposure and IPF, and interaction with a common (minor allele frequency of 9% in European populations) genetic variant associated with IPF,
MUC5B rs35705950, is unknown.
METHODS: Multicentre, incident case-control study. Cases (n=494) were men diagnosed with IPF at 21 UK hospitals. Controls (n=466) were age-matched men who attended a hospital clinic in the same period. Asbestos exposure was assessed at interview using a validated job exposure matrix and a source-receptor model. The primary outcome was the association between asbestos exposure and IPF, estimated using logistic regression adjusted for age, smoking and centre. Interaction with
MUC5B rs35705950 was investigated using a genetic dominant model.
RESULTS: 327 (66%) cases and 293 (63%) controls ever had a high or medium asbestos exposure risk job; 8% of both cases and controls had cumulative exposure estimates ≥25 fibre ml⁻¹ years. Occupational asbestos exposure was not associated with IPF, adjusted OR 1.1 (95% CI 0.8 to 1.4; p=0.6) and there was no gene-environment interaction (p=0.3). Ever smoking was associated with IPF, OR 1.4 (95% CI 1 to 1.9; p=0.04) and interacted with occupational asbestos exposure, OR 1.9 (95% CI 1 to 3.6; p=0.04). In a further non-specified analysis, when stratifying for genotype there was significant interaction between smoking and work in an exposed job (p<0.01) for carriers of the minor allele of
MUC5B rs35705950.
CONCLUSION: Occupational asbestos exposure alone, or through interaction with
MUC5B rs35705950 genotype, was not associated with IPF. Exposure to asbestos and smoking interact to increase IPF risk in carriers of a common genetic variant, the minor allele of
MUC5B rs35705950.
TRIAL REGISTRATION NUMBER: NCT03211507.
KW - Male
KW - Humans
KW - Female
KW - Case-Control Studies
KW - Idiopathic Pulmonary Fibrosis/etiology
KW - Genotype
KW - Occupational Exposure/adverse effects
KW - Asbestos/adverse effects
U2 - 10.1136/oemed-2022-108404
DO - 10.1136/oemed-2022-108404
M3 - Article
C2 - 36635100
SN - 1351-0711
VL - 80
SP - 97
EP - 103
JO - Occupational and Environmental Medicine
JF - Occupational and Environmental Medicine
IS - 2
ER -