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This study investigated the influence of gene-gene and gene-environment interactions on the risk of developing asbestosis. The study comprised 262 cases with asbestosis and 265 controls with no asbestos-related disease previously studied for  MnSOD ,  ECSOD ,  CAT ,  GSTT1 ,  GSTM1 ,  GSTP1 , and  iNOS  polymorphisms. Data on cumulative asbestos and smoking were available for all subjects. To assess gene-gene and gene-environmental interactions, logistic regression was used. The associations between  MnSOD  Ala −9Val polymorphism and the risk of asbestosis and between  iNOS  genotypes and asbestosis were modified by  CAT  –262 C > T polymorphism ( P  = 0.038;  P  = 0.031). A strong interaction was found between  GSTM1 -null polymorphism and smoking ( P  = 0.007),  iNOS  (CCTTT)  n   polymorphism and smoking ( P  = 0.054), and between  iNOS  (CCTTT)  n   polymorphism and cumulative asbestos exposure ( P  = 0.037). The findings of this study suggest that the interactions between different genotypes, genotypes and smoking, and between genotypes and asbestos exposure have an important influence on the development of asbestosis and should be seriously considered in future research on occupational/environmental asbestos-related diseases.

The Influence of Gene-Gene and Gene-Environment Interactions on the Risk of Asbestosis