title: Evaluation of clinical value of single nucleotide polymorphisms of dihydropyrimidine dehydrogenase gene to predict 5-fluorouracil toxicity in 60 colorectal cancer patients in China.
abstract: Dihydropyrimidine dehydrogenase (DPD) activity could be affected by single nucleotide polymorphisms (SNPs), resulting in either no effect, partial or complete loss of DPD activity. To evaluate if SNPs of DPD can be used to predict 5-FU toxicity, we evaluated five SNPs of DPD (14G1A, G1156T, G2194A, T85C and T464A) by TaqMan real time PCR in 60 colorectal cancer patients. Clinical data demonstrated that there was higher correlation between DPD activity and toxic effects of 5-FU (p<0.05). Six patients were positive for G2194A detection, which were all heterozygous. Two patients had lower DPD activities (< 3) with higher toxic effects (≥ stage III) while one patient was also positive for T85C detection. Ten patients were positive for T85C detection. Two patients were homozygous with lower DPD activities and higher toxic effects. Two patients were positive for the T464A detection, which were heterozygous with lower DPD activity and higher toxic effects and also positive for T85C detection. These data clearly indicated that the T464A and homozygous of the T85C are stronger biomarkers to predict the 5-FU toxicity. Our study significantly indicated that the detection for G2194A, T85C and T464A could predict ~13% of 5-FU severe toxic side effects.
authors.affiliation: Department of Hematology and Oncology, China-Japan Union Hospital, Jilin University, Changchun, China, 130041.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Butong
authors.initials: B
authors.lastname: Sun
authors.forename: Zhenxia
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001483:Base Sequence; D002681:China; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D017931:DNA Primers; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000964:Antimetabolites, Antineoplastic; D017931:DNA Primers; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil
keywords: 5-fluorouracil; Dihydropyrimidine-Dehydrogenase (DPD); colorectal cancer; single nucleotide polymorphism (SNP).