Abstract:

Objective To study the relevance between single-nucleotide polymorphism（SNP）of dihydrogenpyrimidine dehydrogenase gene （DYPD） and 5-fluorouracil（5-FU） toxicity in colorectal cancer patients and provide the evidence for individualized treatment in colorectal cancer patients.Methods  The genomic DNA was extracted from EDTA anticoagulation peripheral blood in a total of 60 patients with colorectal cancer and then real-time quantitative polymerase chain reaction (PCR) was performed.The SNPs of 14G1A,G2194A,T85C,G1156T and T464A sites of DPYD were detected,the side effects of chemotherapy with 5-FU in 60 patients were recorded,the relevance between the SNP of DPYD and side effects of 5-FU chemotherapy was analyzed. Results ①14G1A and G1156T polymorphism loci transformation were not found in 60 patients. G2194A heterozygous type was found in 6 cases (10%),wild type in 54 cases (90.0%);T464A heterozygous type in 2 cases (3.3%),wild type in 58 cases (96.7%);T85C mutations type in 2 cases (3.3%),heterozygous type in 8 cases (13.3%),wild type in 50 patients(83.4%).②The incidence of gastrointestinal tract toxicity in patients with T85C polymorphism sites without SNP mutation was 14% (7/50),the incidence of hematological toxicity was 4% (2/50);the incidence of gastrointestinal tract toxicity in patients with T85C polymorphism sites with SNP mutation was 60% (6/10),the incidence of hematological toxicity was 70% (7/10),the differences were statistically significant (P<0.05);the incidences of gastrointestinal reaction andbone marrow restrain in patients with T464A SNP mutation were 50% (1/2) and 100% (2/2),in patients without SNP mutation were 21% (12/58) and 12% (7/58),the differences were statistically significant (P<0.05). ③ The incidences of hematological toxicity and bone marrow restrain in patients with G2194A SNP mutation were33% (2/6) and 50% (3/6), in the patients without SNP mutation were 20% (11/54) and 11 (6/54),the differences were statistically significant (P<0.05). Conclusion The SNP of DPYD has correlation with the adverse reactions of 5-FU chemotherapy.The detection of SNP of DPYD may predict the serious adverse  reactions of 5-FU chemotherapy.

Key words: colorectal neoplasms；dihydrogenpyrimidine dehydrogenase gene；5-fluorouracil；single nucleotide polymorphism