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Review
. 2016 Jul 4;7(11):1421-30.
doi: 10.7150/jca.15480. eCollection 2016.

Gut Microbiota Imbalance and Base Excision Repair Dynamics in Colon Cancer

Debolina Ray  1 , Dawit Kidane  1
Affiliations
Review

Gut Microbiota Imbalance and Base Excision Repair Dynamics in Colon Cancer

Debolina Ray et al. J Cancer. .

Abstract

Gut microbiota are required for host nutrition, energy balance, and regulating immune homeostasis, however, in some cases, this mutually beneficial relationship becomes twisted (dysbiosis), and the gut flora can incite pathological disorders including colon cancer. Microbial dysbiosis promotes the release of bacterial genotoxins, metabolites, and causes chronic inflammation, which promote oxidative DNA damage. Oxidized DNA base lesions are removed by base excision repair (BER), however, the role of this altered function of BER, as well as microbiota-mediated genomic instability and colon cancer development, is still poorly understood. In this review article, we will discuss how dysbiotic microbiota induce DNA damage, its impact on base excision repair capacity, the potential link of host BER gene polymorphism, and the risk of dysbiotic microbiota mediated genomic instability and colon cancer.

Keywords: Base excision repair; Colon cancer.; Microbiota.

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Conflict of interest statement

Competing Interests: The authors have no conflict of interest.

Figures

Figure 1
Figure 1
Possible mechanism of gut microbial impact on genomic instability and Cancer : Many factors including antibiotic use, psychological and physical stress, radiation, and dietary changes can change beneficial members of the gastrointestinal flora (symbiont) and cause disequilibrium of the normal function of (microbiota dysbiosis). The altered bacterial community (pathobiont) in gastrointestinal tract likely release bacterial toxin and /mitogen /bacterial metabolite directly to induce reactive oxygen and nitrogen species (RONs) or indirectly induce chronic inflammation that could result in base damage (represented as red circle). The base damage could be removed by OGG1/MUTYH/TDG/AAG/NEIL1, 2,3, resulting in the formation of AP sites (represented by blue cross mark). AP sites are clustered in close proximity on the opposite strands of the DNA, and processed with AP lyase activity that cleaves the 3' side of AP sites or with APE1 that cleaves the phosphate backbone and generate DSBs that eventually leads to genomic instability and cancer. Furthermore, if DSBs repaired by non-homologous end joining likely trigger genomic instability, cellular transformation and cancer.
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