TY - JOUR
T1 - An evolutionary explanation for antibiotics' association with increased colon cancer risk
AU - Voskarides, Konstantinos
N1 - Publisher Copyright:
© 2022 The Author(s) 2022. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.
PY - 2022
Y1 - 2022
N2 - More than 10 studies have confirmed the association of antibiotic overuse with colorectal cancer. The exact cause is unknown, but most authors hypothesize that disturbance of colon microbiota is the main culprit. In this commentary, an evolutionary explanation is proposed. It is well known that antibiotics can induce antibiotic resistance in bacteria through selection of mutators - DNA mismatch repair deficient (dMMR) strains. Mutators have an increased survival potential due to their high mutagenesis rate. Antibiotics can also cause stress in human cells. Selection of dMMR colon cells may be advantageous under this stress, mimicking selection of bacterial mutators. Concomitantly, mismatch repair deficiency is a common cause of cancer, this may explain the increased cancer risk after multiple cycles of oral antibiotics. This proposed rationale is described in detail, along with supporting evidence from the peer-reviewed literature and suggestions for testing hypothesis validity. Treatment schemes could be re-evaluated, considering toxicity and somatic selection mechanisms. Lay Summary: The association of antibiotics with colon cancer is well established but of unknown cause. Under an evolutionary framework, antibiotics may select for stress-resistant cancerous cells that lack mechanisms for DNA mismatch repair (MMR). This mimics the selection of antibiotic resistant 'mutators' - MMR-deficient micro-organisms - highly adaptive due to their increased mutagenesis rate.
AB - More than 10 studies have confirmed the association of antibiotic overuse with colorectal cancer. The exact cause is unknown, but most authors hypothesize that disturbance of colon microbiota is the main culprit. In this commentary, an evolutionary explanation is proposed. It is well known that antibiotics can induce antibiotic resistance in bacteria through selection of mutators - DNA mismatch repair deficient (dMMR) strains. Mutators have an increased survival potential due to their high mutagenesis rate. Antibiotics can also cause stress in human cells. Selection of dMMR colon cells may be advantageous under this stress, mimicking selection of bacterial mutators. Concomitantly, mismatch repair deficiency is a common cause of cancer, this may explain the increased cancer risk after multiple cycles of oral antibiotics. This proposed rationale is described in detail, along with supporting evidence from the peer-reviewed literature and suggestions for testing hypothesis validity. Treatment schemes could be re-evaluated, considering toxicity and somatic selection mechanisms. Lay Summary: The association of antibiotics with colon cancer is well established but of unknown cause. Under an evolutionary framework, antibiotics may select for stress-resistant cancerous cells that lack mechanisms for DNA mismatch repair (MMR). This mimics the selection of antibiotic resistant 'mutators' - MMR-deficient micro-organisms - highly adaptive due to their increased mutagenesis rate.
KW - adaptation
KW - cancer evolution
KW - DNA repair
KW - MLH1
KW - MSH2
KW - natural selection
UR - http://www.scopus.com/inward/record.url?scp=85132765512&partnerID=8YFLogxK
U2 - 10.1093/emph/eoac018
DO - 10.1093/emph/eoac018
M3 - Article
AN - SCOPUS:85132765512
SN - 2050-6201
VL - 10
SP - 214
EP - 220
JO - Evolution, Medicine and Public Health
JF - Evolution, Medicine and Public Health
IS - 1
ER -