Invited Commentary Invited Commentary: Genes, Environment, and Hybrid Vigor

In the 1950s, case-control studies of smoking and lung cancer established a paradigm for epidemiologic studies of risk factors for chronic diseases. Since then, thousands of case-control studies have examined possible asso-ciations of countless risk factors with numerous diseases, rarely finding associations as strong or consistent as that of smoking with lung cancer. Recently, researchers have applied advances in molecular genetics to conduct candidate gene and genome-wide association studies of lung cancer. Skeptics among both epidemiologists and geneticists have argued that genomic research adds little value when most cases of disease can be attributed to a preventable exposure; however, well-conducted studies of gene-environment interactions that draw on data from more than 50 years of research in toxicology, pathophysiology, and behavioral science offer important models for the development of more comprehensive approaches to understanding the etiology of chronic diseases. case-control studies; DNA damage; DNA repair; genetic predisposition to disease; lung neoplasms; oxoguanine glycosylase 1, human; smoking Abbreviations: hOGG1, human 8-oxoguanine DNA N-glycosylase 1; HuGE, human genome epidemiology. The 20th-century spread of cigarette smoking led to a global epidemic of tobacco-related diseases, which in 2000 killed more than 4 million people worldwide (1)