Interplay between DNA repair and inflammation, and the link to cancer

Abstract

DNA damage and repair are linked to cancer. DNA damage that is induced endogenously or from exogenous sources has the potential to result in mutations and genomic instability if not properly repaired, eventually leading to cancer. Inflammation is also linked to cancer. Reactive oxygen and nitrogen species (RONs) produced by inflammatory cells at sites of infection can induce DNA damage. RONs can also amplify inflammatory responses, leading to increased DNA damage. Here, we focus on the links between DNA damage, repair, and inflammation, as they relate to cancer. We examine the interplay between chronic inflammation, DNA damage and repair and review recent findings in this rapidly emerging field, including the links between DNA damage and the innate immune system, and the roles of inflammation in altering the microbiome, which subsequently leads to the induction of DNA damage in the colon. Mouse models of defective DNA repair and inflammatory control are extensively reviewed, including treatment of mouse models with pathogens, which leads to DNA damage. The roles of microRNAs in regulating inflammation and DNA repair are discussed. Importantly, DNA repair and inflammation are linked in many important ways, and in some cases balance each other to maintain homeostasis. The failure to repair DNA damage or to control inflammatory responses has the potential to lead to cancer.

The role of estradiol metabolism in urogenital schistosomiasis-induced bladder cancer

“…63 Consequently, these metabolites of estrogens derived from the parasite might behave as chemical carcinogens. 47 In addition, there may be "classical" hormone-like effects of these metabolites on the endocrine and immune system of the host; the ER activity was suppressed in urothelial cells cultured in vitro and in the bladders of mice exposed to S. haematobium antigens.…”

Systematic review on the association between ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms and glioma risk

“…Thus, efficient DNA repair is required to prevent the propagation of errors and to maintain genomic stability (Kidane et al, 2014). Damage repair involves more than 130 genes and several molecular pathways, including nucleotide excision repair (NER), base-excision repair, homologous recombination, and nonhomologous end joining (Kidane et al, 2014). Thus, polymorphisms in DNA repair genes may cause a defect in DNA repair and subsequently influence an individual's susceptibility to carcinogenesis (Higgins et al, 2003).…”

“…Thus, efficient DNA repair is required to prevent the propagation of errors and to maintain genomic stability (Kidane et al, 2014). Damage repair involves more than 130 genes and several molecular pathways, including nucleotide excision repair (NER), base-excision repair, homologous recombination, and nonhomologous end joining (Kidane et al, 2014).…”

“…Thus, polymorphisms in DNA repair genes may cause a defect in DNA repair and subsequently influence an individual's susceptibility to carcinogenesis (Higgins et al, 2003). Excision repair cross complementation group 1 (ERCC1) and ERCC2, 2 DNA repair genes whose products are important in the NER, are located on chromosome 19q13.3 (Kidane et al, 2014).…”

Inflammation-induced DNA damage and damage-induced inflammation: a vicious cycle

“…On the other hand, ROS can directly damage or inhibit proteins of these processes as well 111,112 . In chronic inflammation, persistently high ROS level, reduced repair efficiency and dysfunctional mitochondrial respiration can lead to the accumulation of DNA damage 113 .…”