Interactions of Environmental Risk Factors and Genetic Variations: Association with Susceptibility to Cancer

The biological mechanisms of cancer development involve both environmental and genetic factors. Among the environmental factors, tobacco and alcohol have been established as one of the most potent causative factors in promoting carcinogenesis while genetic variations in phase I and phase II xenobiotic metabolizing enzymes (XMEs) play an important role in determining the outcome of exposure to environmental carcinogens. The genes that contribute to cancer development fall into three broad categories, namely tumor suppressor genes, oncogenes, and DNA repair genes though several other genes are also involved. Cytochrome P450s (CYPs) are the most important super family of phase I XMEs while phase II Glutathione S-transferases (GSTs) conjugate a wide range of electrophilic substrates with the abundant cellular nucleophile-glutathione (GSH) promoting their metabolism, detoxification, and excretion. There has been a lot of interest in unravelling gene–environment interactions, i.e. whether the risk of cancer associated with a particular environmental exposure such as tobacco and alcohol differs with respect to functionally different polymorphisms of these genes. A large number of studies have been conducted involving several genes and many cancers and the results, though sometimes inconsistent, help in advancing the etiological understanding of cancer. Study of gene–environment interaction is important for improving accuracy and precision in the assessment of both genetic and environmental influences in promoting cancer. Gene–environment interaction also has important implications for public health as it helps in predicting cancer rates and provides a basis for appropriate recommendations for cancer prevention.