Inflammation as Cause for Scar Cancers of the Lung

Abstract

The molecular and cellular basis of inflammation has become a topic of great interest of late because of the association between mechanisms of inflammation and risk for cancer. Inflammatory-mediated events, such as the production of reactive oxygen species (ROS), the activation of growth factors (for wound repair), and the altering of signal-transduction processes to activate cell-proliferation (to replace necrotic/apoptotic tissue cells), events that also can occur independently of inflammation, are all considered to be components of risk for a variety of cancers. Using scar cancer of the lung as an example, mechanisms of inflammation associated with recurring infections with Mycobacterium tuberculosis are discussed in the context that they may, in fact, be the major or sole cause of a cancer. Production of ROS, prostaglandins, leukotrienes, and cytokines in pulmonary tissues is greatly enhanced due to a cell-mediated immune response against macrophages infected with M. tuberculosis . These responses lead to the extensive fibrosis associated with recurring infections, possibly leading to decreased clearance of lymph and lymph-associated particles from the infected region. They also will enhance rates of cell division by inhibiting synthesis of P21, leading to enhanced progression from G0 arrest to G1 phase, from G1 to Sphase, and from G2 to M phase of the cell cycle. By increasing rates of oxidative DNA damage and inhibiting apoptosis by enhancing synthesis of BCL-2, mutagenesis of progeny cells is enhanced, and these effects coupled with enhanced angiogenesis stimulated by COX-2 products lead to an environment that is highly conducive to tumorigenesis. Based on the evidence, it appears that but for an inflammatory response to recurring infections, some cases of scar cancer would not exist. By making appropriate lifestyle and dietary changes, a variety of anti-inflammatory effects can be produced, which should attenuate inflammation-induced risk for cancer.