Gene-Environment Interactions: The Case of Asbestosis

Abstract

It is becoming evident that both environmental/lifestyle and genetic factors may influence the development of many diseases. This chapter highlights the importance of considering gene-environment interactions, which is shown on the example of our studies into asbestosis, one of the most frequent asbestos-related diseases. Asbestos fibres induce generation of reactive oxygen and nitric species (ROS and RNS), and it is generally accepted that ROS and RNS are involved in the pathogenesis of asbestos-related diseases. Human tissues contain specific enzymes that metabolise ROS and RNS, such as superoxide dismutases (SODs), catalase (CAT), glutathione-S-transferases (GSTs) and inducible nitric oxide synthase (iNOS). As these enzymes are encoded by polymorphic genes, genetic variability in an individual's capacity to detoxify these reactive species may modify the risk for disease. Our previous studies into asbestosis showed that the associations between the risk of asbestosis and MnSOD Ala-9Val polymorphism and between asbestosis and iNOS genotypes were modified by CAT -262C>T polymorphism. A strong interaction was also found between smoking (lifestyle factor) and GSTM1-null polymorphism, between smoking and iNOS (CCTTT)n polymorphism and between cumulative asbestos exposure (environmental factor) and iNOS (CCTTT)n polymorphism. The findings of our studies and other studies indicate that in addition to environmental and/or occupational exposure to different hazards and lifestyle factors, genetic factors as well as the interactions between different genotypes, between genotypes and lifestyle factors and between genotypes and environmental/occupational exposure to hazards may also have an important role on the development of diseases and should be further investigated.