Epidemiological and other scientific investigations have clearly implicated tobacco smoking as the primary cause of lung cancer, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. Many lines of evidence consistently support a hereditary influence on lung cancer risk, with polygenic mechanisms and complex interactions, including epistatic relationships [3]. Over 100 studies have examined individual candidate genes in relation to lung cancer during the last decade. Despite this body of literature, no clear consensus exists on the role these factors play in influencing lung cancer susceptibility. The vast majority of published studies in this field have been underpowered in relation to the realistic main and interactive effects suggested by recent metanalyses [4-6]. In addition, they have been focused only on a few genes or few risk factors, whereas many genes and interactions between genes and other risk factors are likely important for lung carcinogenesis.
