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While smoking is the major exposure that greatly increases lung cancer risk, the sources of interindividual variability that confer particularly higher risks to some individuals have not yet been elucidated. Refining our knowledge of the genes and pathways that jointly increase lung cancer risk in the context of tobacco smoke or other environmental exposures will provide new insights into the etiology of lung cancer. The potential public health benefits from identifying subgroups of the population at high risk for this lethal disease are large. Our state of the art analytical team will develop novel approaches for identifying individuals at high risk for lung cancer. Identification of genes involved in lung cancer in smokers would contribute identifying individuals at highest risk for lung cancer development who could benefit from screening and may further our understanding of the tobacco carcinogenic process.

Proposal Overview: The scientific scope of the proposal comprises a series of three integrated and interdependent research areas with the unifying theme of identifying, replicating and functionally validating genomic regions associated with lung cancer susceptibility in different ethnic subgroups. To accomplish these goals, we propose to create an infrastructure for the integration of data from multiple genome scans and to promote replication and validation studies of the effects of genetic and environmental factors influencing lung cancer risk. Area 1 is the Discovery arm that aims at identifying novel variants, replicating and pooling original GWA findings, and conducting fine mapping studies. Existing studies have identified genomic regions that contain loci that are excellent candidates to affect lung cancer susceptibility, but the precise mechanisms of action remain unknown and are the focus for biological studies in this proposal in Area 2. Provides novel opportunities for the integration of population science with biological studies to provide a comprehensive assessment of mechanisms and effects on lung cancer etiology of genetic factors. Area 3 will conduct the in depth epidemiologic analyses focusing on gene-environmental interactions and constructing risk assessment models.

by Dr. Radut