Association Of MTHFR C677T Polymorphism With Susceptibility To Colorectal Cancer And With5-FU-based Chemotherapy Related-toxicity

Objectives: To investigate the association of MTHFR C677T polymorphism withgenetic susceptibility to colorectal cancer, and the relationship between the polymorphismand5-FU-based chemotherapy related-toxicity.Methods: DNA was extracted from84controls’ peripheral blood and106cases’peripheral blood, normal intestinal mucosa tissue and colorectal cancer tissue.The MTHFRC677T genotypes were determined by DNA sequencing technique. The associationbetween the MTHFR C677T polymorphism and risk of colorectal cancer was evaluated,and the relationship between the polymorphism and5-FU-based chemotherapyrelated-toxicity was analyzed combined with clinical and follow-up materials.Results:(1) MTHFR C677T CT and TT genotypes did not significantly increasethe risk of colorectal cancer compared with CC genotype (TT vs. CC: OR=1.335,95%CI0.699-2.549; TT vs.CC: OR=1.338,95%CI0.557-3.218). There was also no obviousevidence that T allele could effect colorectal cancer risk(T-allele vs. C-allele: OR=1.171,95%CI0.777-1.766).(2) The genotypes of normal intestinal mucosa tissue and peripheral blood wereconsistent. In colorectal cancer tissue, reverse mutation was found, the frequency of whichwas13.2%. The frequency of reverse mutation in TT genotype (44.4%) was significantlyhigher than in CT genotype (10.3%). The reverse mutation had no correlation with genders,ages, tumor locations, histological types or clinical pathological stages.(3) The incidence rates of nausea/vomiting in TT genotype patients (77.8%) wassignificantly higher than CC (35.5%) and CT (30.0%) genotype patients (P＜0.05), whenpatients were treated with5-FU-based chemotherapy. There was no association of MTHFR C677T polymorphism with myelosuppression, diarrhea, mucositis or hand-footsyndrome.(P＞0.05).Conclusions:(1) There is no evidence that MTHFR C677T polymorphism isassociated with colorectal cancer risk.(2) Reverse mutation may take place in the process of tumorigenesis and developmentof colorectal cancer. Reverse mutation is more likely to take place in TT genotype.Whether it is related to genders, ages, tumor locations, histological types and clinicalpathological stages remains unknow. Why colorectal cancer shows reverse mutation needto be cleared.(3) MTHFR C677T polymorphism may predict the risk of nausea/vomiting forpatients who will be treated5-FU-base chemotherapy.