Could removing arsenic from tobacco smoke significantly reduce smoker risks of lung cancer?
Cox LA. Risk Analysis 29(1): 3-17, 2009. (61 refs.) If a specific biological mechanism could be determined by which a carcinogen increases lung cancer risk, how might this knowledge be used to improve risk assessment ? To explore this issue, we assume (perhaps incorrectly) that arsenic in cigarette smoke increases lung cancer risk by hypermethylating the promoter region of gene p16INK4a, leading to a more rapid entry of altered (initiated) cells into a clonal expansion phase. The potential impact on lung cancer of removing arsenic is then quantified using a three-stage version of a multistage clonal expansion (MSCE) model. This refines the usual two-stage clonal expansion (TSCE) model of carcinogenesis by resolving its intermediate or “initiated” cell compartment into two subcompartments, representing experimentally observed “patch” and “field” cells. This refinement allows p16 methylation effects to be represented as speeding transitions of cells from the patch state to the clonally e
