Population structure, ancestry, and environmental predictors of lung and bladder cancer in New Hampshire

Complex diseases such as lung cancer are most commonly the result of environmental variables acting on an individual's genetic background. Those environmental variables may be found in the external environment, such as exposures to carcinogenic materials at work or the result of personal behaviors such as smoking or nutrition. The interaction between genetics, personal and external environment constitute the triangle of human ecology. In this work, bladder and lung cancer are examined using genetic data as well as multiple types of environmental data within two different New Hampshire (NH) sample populations. Initially, a review of spatial methods that may be employed in investigations of gene-environment interaction is presented including the call for a new paradigm of study called "ecogeographic genetic epidemiology". Subsequently, an analysis of genetic substructure in NH showing six distinct subpopulations also shows that eastern European populations are still genetically discernible within this ancestrally mixed Caucasian population. These results are further explored with an association analysis of ancestry and genetic markers in relation to bladder cancer. Environmental variables are then explored spatially using lung cancer data from Vermont and New Hampshire, and finally combined with air pollution maps to investigate spatial variation in models of gene-environment interaction. Conclusions suggest that the ecogeographic genetic epidemiology approach can give more in-depth perspectives into complex disease etiology than traditional approaches.