MPO promoter polymorphism rs2333227 enhances malignant phenotypes of colorectal cancer by altering the binding affinity of AP-2{alpha}

Myeloperoxidase (MPO) promoter single nucleotide polymorphisms (SNPs) rs2243828 (-764T>C) and rs2333227 (G-463A) program malignant phenotypes by regulating MPO transcriptional activity. In this study, we enrolled a total of 1,175 controls and 1,078 colorectal cancer (CRC) patients with comprehensive clinical and survival information to assess whether these SNPs could affect the susceptibility and development of CRC. The MPO rs2333227 TT genotype significantly increased the risk of CRC and decreased the overall survival time of patients. CRC cells with the rs2333227 TT genotype exhibited enhanced proliferation, migration, and invasion capacity in vitro and in vivo. Mechanistically, we found that MPO SNP rs2333227 C to T mutation altered the binding affinity of the transcription factors AP-2α to the rs2333227 mutation region, sequentially enhancing expression levels of MPO and activating further IL23A-MMP9 axis-mediated oncogenic signaling. Taken together, our findings indicate that MPO SNP rs2333227 serves as a marker of enhanced risk for development of CRC.

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