Ming Xu1, Yan Gao2, Tingting Yu3, Jirong Wang4, Liang Cheng1, Lifang Cheng1, Dawei Cheng5, Baoli Zhu6. 1. Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, China. 2. Suzhou Center for Disease Prevention and Control, Suzhou, China. 3. Department of Developmental Genetics, Nanjing Medical University, Nanjing, China. 4. Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. 5. Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, China. Electronic address: chendawei@syphu.edu.cn. 6. Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, China. Electronic address: zhubl@jscdc.cn.
Abstract
BACKGROUND: The mammalian target of rapamycin (mTOR) plays an important role in the development and progression of colorectal cancer (CRC). Recently, a functional polymorphism (rs2295080 T>G) in the promoter of MTOR has been shown to influence its expression and confer susceptibility to cancer. Therefore, in the present study, we sought to investigate the influence of this polymorphism on the risk of CRC. METHODS: We genotyped this polymorphism by using the TaqMan method in a case-control study comprising of 737 CRC patients and 777 controls. The logistic regression was used to assess the genetic association with occurrence of CRC. The functionality of the polymorphism was examined by luciferase reporter assay. RESULTS: We found the variant genotypes of MTOR rs2295080 (TG/GG) were significantly associated with decreased CRC risk, compared with the wild genotype [TG/GG vs. TT: adjusted odds ratio (OR)=0.76, 95% confidence interval (CI)=0.62-0.94, P=0.011], and the protective effect of this polymorphism was more predominant among the subgroups of elder (OR=0.66, 95% CI=0.49-0.89) and male (OR=0.63, 95% CI=0.48-0.84) subjects. Furthermore, the luciferase reporter assay showed that the rs2295080G allele significantly decreased the luciferase activity in both sw480 and sw620 cell lines (P=0.002 and P<0.001, respectively). CONCLUSIONS: Our results suggest that the functional rs2295080 T>G in the promoter of MTOR may influence the susceptibility of CRC in the Chinese population through regulating the transcription activity of MTOR promoter. Large population-based prospective studies are required to validate our findings.
BACKGROUND: The mammalian target of rapamycin (mTOR) plays an important role in the development and progression of colorectal cancer (CRC). Recently, a functional polymorphism (rs2295080 T>G) in the promoter of MTOR has been shown to influence its expression and confer susceptibility to cancer. Therefore, in the present study, we sought to investigate the influence of this polymorphism on the risk of CRC. METHODS: We genotyped this polymorphism by using the TaqMan method in a case-control study comprising of 737 CRC patients and 777 controls. The logistic regression was used to assess the genetic association with occurrence of CRC. The functionality of the polymorphism was examined by luciferase reporter assay. RESULTS: We found the variant genotypes of MTORrs2295080 (TG/GG) were significantly associated with decreased CRC risk, compared with the wild genotype [TG/GG vs. TT: adjusted odds ratio (OR)=0.76, 95% confidence interval (CI)=0.62-0.94, P=0.011], and the protective effect of this polymorphism was more predominant among the subgroups of elder (OR=0.66, 95% CI=0.49-0.89) and male (OR=0.63, 95% CI=0.48-0.84) subjects. Furthermore, the luciferase reporter assay showed that the rs2295080G allele significantly decreased the luciferase activity in both sw480 and sw620 cell lines (P=0.002 and P<0.001, respectively). CONCLUSIONS: Our results suggest that the functional rs2295080 T>G in the promoter of MTOR may influence the susceptibility of CRC in the Chinese population through regulating the transcription activity of MTOR promoter. Large population-based prospective studies are required to validate our findings.
Authors: Colinda C J M Simons; Leo J Schouten; Roger W L Godschalk; Frederik-Jan van Schooten; Monika Stoll; Kristel Van Steen; Piet A van den Brandt; Matty P Weijenberg Journal: BioData Min Date: 2022-01-10 Impact factor: 2.522