Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B_(12) status

作     者：Pooneh Mokarram Fakhraddin Naghibalhossaini Mehdi Saberi Firoozi Seyed Vahid Hosseini Ahmad Izadpanah Heshmetalah Salahi Seyed Ali Malek-Hosseini Abdoulrasool Talei Mehra Mojallal 

作者机构：Department of BiochemistryShiraz University of Medical SciencesSchool of MedicineShiraz 71345Iran Department of Internal Medicine and Gastroenterohepatology Research CentreShiraz University of Medical SciencesShiraz 71345Iran Department of Surgery(colorectal ward) and Gastroenterohepatology Research CentreShiraz University of Medical SciencesShiraz 71345Iran Department of Surgery and Organ Transplantation Research CentreNamazee HospitalShiraz University of Medical SciencesShiraz 71345Iran Department of Surgery and Institute of Cancer ResearchShiraz University of Medical SciencesShiraz 71345Iran Pathology LaboratoryDena HospitalShiraz 71345Iran 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2008年第14卷第23期

页      面：3662-3671页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：The office of the Vice Chancellor for Research, Shiraz University of Medical Sciences, No. 83-2212 Grant from the Gastroenterohepatology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran 

主　　题：Metthylentetrahydrofolate reductase Folate Vitamin 1322 Methylation Colorectal cancer 

摘      要：AIM:To evaluate joint effects of Methylentetra-hydrofolate reductase(MTHFR) C677T genotypes,and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients. METHODS:We examined the associations between MTHFR C677T genotype,and promoter methylation of P16,hMLH1,and hMSH2 tumor-related genes among151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B12 concentrations by a commercial radioimmunoassay kit. RESULTS:We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison,we did not find a significant association between methylation in tumors and any single genotype. However,in comparison to controls with the CC genotype,an increased risk of tumor methylation was associated with the CT genotype(OR = 2.5;95% CI,1.1-5.6) . In case-case comparisons,folate/vitamin B12 levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high(above median) versus low(below median) serum folate/vitamin B12 levels were 4.9(95% CI,1.4-17.7) ,and 3.9(95% CI,1.1-13.9) ,respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group,especially in those with MTHFR CT(P = 0.01) ,and CT/TT(P = 0.002) genotypes,but not in those with the CC genotype(P = 1.0) . CONCLUSION:We conclude that high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes,and this relationship is modified by MTHFR C677T genotypes.