The development of cancer in various organs is often associated with chronic inflammation, imposing a very strong relationship between inflammation and carcinogenesis. Abnormal cellular alterations involved in inflammation including oxidative stress, gene mutations, epigenetic changes, and inflammatory cytokine induced cell proliferation have been shared with carcinogenic process, leading to seek for a critical pathway connecting inflammation and cancer in order to develop a powerful tool for preventing cancer development through bio-regulating inflammatory process. In this review article, a summary of GI cancers linked to chronic inflammation is presented. Transforming growth factor (TGF)-Ղ₁ is a potent growth inhibitor with tumor suppressing activity. Cancers are often refractory to this growth inhibition either because of genetic loss of TGF-Ղ signaling molecules or because of downstream perturbation of TGF-Ղ adaptors. On the other hand, carcinomas often secrete excess TGF-Ղ₁ and respond to it by enhanced invasion, immune surveillance, and metastasis. Therefore, subtle modification of therapeutic approaches should be seek to inhibit TGF-Ղ induced invasive phenotype, but also retain its growth inhibitory, apoptosis inducing, and anti-inflammatory effects. (Cancer Prev Res 14, 177-187, 2009)

Keywords: TGF-Ղ,, Chemoprevention, Inflammation, Carcinogenesis, GI cancers