Reactive oxygen species (ROS)--induced genetic and epigenetic alterations in human carcinogenesis.

Cancer is a multistage and complex process characterized by molecular alterations that underlie all three phases of its development: (i) initiation, (ii) promotion and (iii) progression. Some of these molecular events include alterations in gene expression that are regulated by both genetic and epigenetic mechanisms. On the other hand, "oxidative stress" implies a cellular state where ROS production exceeds the cell's ability to metabolize them resulting in excessive accumulation of ROS that overwhelms cellular defenses. Such state has been shown to regulate both genetic and epigenetic cascades underlying altered gene expression in human disease including cancer. Throughout this manuscript, we review the current state of knowledge on the role of ROS-induced oxidative stress in altering the genetic and epigenetic involvement during human carcinogenesis. 2011 Elsevier B.V. All rights reserved.