While linkage studies of hereditary syndromes have succeeded in identifying rare but high-penetrant gene mutations, there’s been a recent shift to population or association studies designed to detect common but low-penetrant gene variants. That started with a flurry of studies to identify the risks associated with candidate genes, selected because of their known function and their functional relevance to cancer. Shown here are some gene variants, including those that affect high-risk behaviors such as smoking addiction and pathways to obesity. The metabolism of exogenous or endogenous carcinogens, and molecular mechanisms affecting cancer risks are the adjacent stromal cells in the micro environment. While the studies are designed to evaluate both candidate genes and exposure data in the search for interactions, simply knowing the substrate of the variants may provide inferences into the environmental or host factors that raise or lower the risk of cancer.