Inflammation-associated genomic instability in cancer

Abstract

Inflammation is essential in protecting us against foreign pathogens. However when left unchecked, it becomes chronic inflammation, a potential precursor to carcinogenesis. While inflammatory signalling provides pro-survival stimuli, it also causes genomic instability and allows mutant cells to escape cell cycle arrest and apoptosis. This occurs through the release of reactive oxygen/nitrogen species (ROS/RNS), the increased expression of activation-induced cytidine deaminase (AID), inhibition of p53 function and the reactivation of TERT expression. Because chronic inflammation can ultimately lead to genomic instability, there is a need to target chronic inflammation, through the suppression of effector pathways with biologics or small molecules. More recently, therapies have also focused on stimulating physiological resolution, which offers a promising, tissue-specific alternative. As we better understand the triggers of chronic inflammation, therapies can be more specific, without compromising the overall functions of our immune system.

The association of prediagnostic circulating levels of cardiometabolic markers, testosterone and sex hormone‐binding globulin with risk of breast cancer among normal weight postmenopausal women in the UK Biobank

“…Several biological mechanisms may explain the associations between the analytes studied here and risk of postmenopausal breast cancer. An inflammatory microenvironment has been directly linked to various processes including oxidative stress, DNA damage and genomic instability which have been associated with the initiation of cancer 37,38 . Moreover, most postmenopausal breast tumors are estrogen‐sensitive, and, importantly, some studies have found that inflammation is associated with processes that lead to increased estrogen signaling.…”

Helicobacter pylori infection induced genome instability and gastric cancer

“…The main inflammatory pathways include the non-canonical and canonical NF-κB, JAK-STAT and MAPK signaling pathways. Activation of each or combined pathways eventually drives abnormal gene transcription that has been implicated in cancer development (Pua et al 2019). Even though no evidence showed a direct role of NF-κB signaling in gastric cancer stem cells, aberrant activation of the pathway contributes to increased proliferation and evasion of apoptosis, which could contribute to tumorigenesis (Kang et al 2008;Liu et al 2004).…”

“…ROS production has been observed in patients and cultured cells infected with H. pylori (Davies et al 1994;Drake et al 1998). The sustained release of ROS/ RNS together with other risk factors including increased activation-induced cytidine deaminase (AID), inhibited p53 and reactivated TERT expression contribute to DNA damage and genomic instability during chronic inflammation (Pua et al 2019).…”

Malignancy Risk of Immunoglobin G4-related Disease: Evidence From a Large Cohort Multicenter Study

“…According to previous studies [16][17][18][19][20], mediators produced by activated in ammatory cells promote a variety of damages, including genetic mutations, post-translational modi cation of proteins involved in apoptosis, DNA repair, cell cycle control and signal transduction, as well as DNA and histone methylation, generating a pathologically conducive microenvironment which may induce the growth and progression of malignancies. Several previous studies suggested that chronic antigenic stimulation, together with oncogenic events such as p53 inactivation and K-ras mutation in IgG4-RD led to an increased risk of malignant transformation compared with the general population [6,21].…”