biostudies-literatureMeng QNatural science Foundation of Jiangsu Higher Education InstitutionsFundamental Research Funds for the Central UniversitiesSix talent peaks project in Jiangsu ProvinceFund of the Distinguished Talents of Jiangsu ProvinceNIEHS NIH HHSFund of the post-graduate Innovative TalentsNational Natural Science Foundation of China (NSFC)Natural Science Foundation of Jiangsu Province (Jiangsu Natural Science Foundation)HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)National key research and development program of china2760-2769https://www.ebi.ac.uk/biostudies/studies/S-EPMC6084780biostudies-literatureUnknown78(10)Myeloperoxidase (MPO) promoter 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 patients with colorectal cancer with comprehensive clinical and survival information to assess whether these SNPs could affect the susceptibility and development of colorectal cancer. The MPO rs2333227 TT genotype significantly increased the risk of colorectal cancer and decreased the overall survival time of patients. Colorectal cancer 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 colorectal cancer.Significance: MPO polymorphisms are a guide for high risk and poor prognosis in patients colorectal cancer. Cancer Res; 78(10); 2760-9. ©2018 AACR.Cancer researchMPO Promoter Polymorphism rs2333227 Enhances Malignant Phenotypes of Colorectal Cancer by Altering the Binding Affinity of AP-2α.PMC608478081472938,and 91643109BK20151418， and BK20171060R01 ES0105638170326117KJB3300022017YFC0211600,and 2017YFC0211603R01 ES007331KYZZ16_0137R01 ES020852BK201500212016-WSN-002R01 ES10563,R01 ES07331 and R01 ES020852Yang HLi XAschner MMeng QGao NWu STang BWang YSun HChen RXu JLu RfalseMPO Promoter Polymorphism rs2333227 Enhances Malignant Phenotypes of Colorectal Cancer by Altering the Binding Affinity of AP-2α.Myeloperoxidase (MPO) promoter 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 patients with colorectal cancer with comprehensive clinical and survival information to assess whether these SNPs could affect the susceptibility and development of colorectal cancer. The MPO rs2333227 TT genotype significantly increased the risk of colorectal cancer and decreased the overall survival time of patients. Colorectal cancer 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 colorectal cancer.Significance: MPO polymorphisms are a guide for high risk and poor prognosis in patients colorectal cancer. Cancer Res; 78(10); 2760-9. ©2018 AACR.2018-01-01T00:00:00Z2018 May2024-11-21T06:19:36.206Z2019-06-06T23:04:02ZS-EPMC60847802954040210.1158/0008-5472.CAN-17-253810.1158/0008-5472.can-17-2538