Mechanisms for nicotine in the development and progression of gastrointestinal cancers

Abstract

Long-term smoking is major risk factor for a variety of cancers, including those of the gastrointestinal (GI) tract. Historically, nicotine and its derivatives are well known for their role in addiction, and have more recently been documented for their carcinogenic role in a number of human cancers. The cellular and molecular pathways activated by nicotine mimic physiological and environmental carcinogenesis in cancers throughout the GI tract potentiating cancer growth and/or inducing the formation of cancer on their own. Thus, it is important to unlock the carcinogenic mechanisms induced by nicotine in these systems, and underscore nicotine's potential as an environmental hazard. This review outlines the specific pathways demonstrated to mediate nicotine's carcinogenic mechanism in the GI tract. The abundance of cell and animal evidence calls for increased epidemiologic and case-control evaluation of nicotine's role in cancer.

Figure 1

Overview of the major mechanisms nicotine enhances cancer in the GI tract. Nicotine stimulation through the α7-nAChR induces a change in the expression of surface receptors, release of growth factors, and directly invokes transduction of growth pathways. This leads to an increase in mediators of cell proliferation, angiogenesis, and metastasis, and a decrease in apoptosis.