An Overview of Disease and Health Research Vol. 12

Microsomal epoxide hydrolase (mEH), encoded by the EPHX1 gene, represents a critical enzyme in xenobiotic metabolism, functioning at the interface between detoxification and metabolic activation of environmental carcinogens. In addition to its role in metabolising environmental xenobiotics, mEH regulates endogenous epoxide-containing compounds involved in various physiological processes. This review aims to discuss the role of microsomal epoxide hydrolase in lung cancer. mEH plays a pivotal role in the pulmonary metabolism of carcinogenic compounds derived from tobacco smoke and environmental pollutants. By converting reactive epoxide intermediates into more stable dihydrodiols, the enzyme contributes to cellular protection; however, it may also facilitate the formation of highly reactive dihydrodiol-epoxides, thereby promoting carcinogenesis. Thus, mEH activity reflects a complex balance between detoxification and bioactivation pathways. Accumulating epidemiological and molecular evidence indicates that genetic polymorphisms within the EPHX1 gene significantly influence individual susceptibility to lung cancer. Functional variants such as Tyr113His and His139Arg alter enzyme activity and affect the metabolic processing of carcinogenic compounds. The relationship between EPHX1 polymorphisms and lung cancer risk also appears to vary according to ethnic background and tumour histology. Reduced microsomal epoxide hydrolase activity has been proposed as an important factor influencing susceptibility to carcinogen-induced lung damage, and given the central role of xenobiotic metabolism in lung carcinogenesis, preventive strategies that reduce exposure to environmental carcinogens are the most effective approach to lowering disease risk. Electronic databases such as PubMed, Scopus, and Google Scholar were systematically searched to compile the information, but current evidence is restricted by small, ethnically homogeneous cohorts and inconsistent experimental designs. Advances in molecular genetics and multi-omics approaches, including genomics, transcriptomics, proteomics, and metabolomics, offer new opportunities to better understand xenobiotic metabolic networks and identify individuals at increased risk. Such insights may support the development of targeted prevention strategies, early screening programs, and personalised interventions to reduce lung cancer incidence.