Gene-environment interactions in human lung cancer risk

Genetically determined factors that abrogate the effects of environmental carcinogens may explain differences in susceptibility. The challenge in risk assessment is to account for interindividual variation in susceptibility to carcinogens. The main focus in this project is on gene – environment interactions and susceptibility genes. Since the human genome has been sequenced it is now feasible to approach these questions and the identification of genes that contribute to increased sensitivity to xenobioti ca in the environment. We use lung cancer as a model in our studies since the major risk factor is known and less than 20% of long-term smokers develop lung cancer by age 75. The purpose of the project is to investigate candidate genes for susceptibility to chronic lung inflammation since the contribution of chronic inflammation to lung cancer development may be substantial. Oxidative stress seems to be involved in a large number of diseases. We will also examine responses at gene expression level in the lung to tobacco smoke and possible relation to cancer susceptibility and continue our studies on susceptibility in molecular-epidemiological studies in a candidate gene approach.