Smoking and lung cancer: the role of inflammation.
Worldwide over 1 million people die due to lung cancer each year. It is estimated that cigarette smoking explains almost 90% of lung cancer risk in men and 70 to 80% in women. Clinically evident lung cancers have multiple genetic and epigenetic abnormalities. These abnormalities may result in activation of oncogenes and inactivation of tumor-suppressor genes. Chronic inflammation, which is known to promote cancer, may result both from smoking and from genetic abnormalities. These mediators in turn may be responsible for increased macrophage recruitment, delayed neutrophil clearance, and increase in reactive oxygen species (ROS). Thus, the pulmonary environment presents a unique milieu in which lung carcinogenesis proceeds in complicity with the host cellular network. The pulmonary diseases that are associated with the greatest risk for lung cancer are characterized by abundant and deregulated inflammation. Pulmonary disorders such as chronic obstructive pulmonary disease (COPD)/emphysema are characterized by profound abnormalities in inflammatory and fibrotic pathways. The cytokines and growth factors aberrantly produced in COPD and the developing tumor microenvironment have been found to have deleterious properties that simultaneously pave the way for both epithelial-mesenchymal transition (EMT) and destruction of specific host cell-mediated immune responses. Full definition of these pathways will afford the opportunity to intervene in specific inflammatory events mediating lung tumorigenesis and resistance to therapy.
Walser
Tonya
T
Lung Cancer Research Program, Division of Pulmonary and Critical Care Medicine, 37-131 CHS, 10833 Le Conte Avenue, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1690, USA.
Cui
Xiaoyan
X
Yanagawa
Jane
J
Lee
Jay M
JM
Heinrich
Eileen
E
Lee
Gina
G
Sharma
Sherven
S
Dubinett
Steven M
SM
D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology*; D008175:Lung Neoplasms / Q000209:etiology*; D008297:Male; D012907:Smoking / Q000009:adverse effects*