DPYD genotype and haplotype analysis and colorectal cancer susceptibility in a case-control study from Slovakia

Gen Physiol Biophys. 2017 Dec;36(5):557-563. doi: 10.4149/gpb_2017046.


Dihydropyrimidine dehydrogenase (DPD) acts as the first-step enzyme catabolizing pyrimidines in vivo. DPYD gene mutations interfere with the breakdown of uracil and thymine. Genetic variations of DPYD can cause an enzyme deficiency state, which results in severe toxicity or other adverse side effects such as DNA damage or RNA damage caused by imbalance of the nucleotide pool. Our case-control study investigates the possible association between seven DPYD gene polymophisms (rs1801267, rs72547602, rs1801160, rs3918290, rs1801159, rs1801158, rs1801265) and risk of colorectal cancer (CRC). The association analysis for DPD was performed on 273 CRC patients and 187 healthy controls. There is significant allele association of SNP rs1801160 with colorectal cancer (p = 0.003, OR = 3.264, 95% CI = 1.425-7.475) in present analysis. Haplotype analysis of four DPYD polymorphisms showed significant difference in the distribution "IISt" haplotype between cases and controls. In comparison to the most common haplotype (VISt), the "IISt" haplotype was associated with increased risk for CRC (p = 0.038, OR = 2.733, 95% CI = 1.019-7.326). The present study suggests that the SNP rs1801160 and the "IISt" haplotype in the DPYD gene may also have a role in colorectal cancer risk.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / genetics*
  • Dihydrouracil Dehydrogenase (NADP) / genetics*
  • Female
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / epidemiology*
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Prevalence
  • Prognosis
  • Reproducibility of Results
  • Risk Assessment
  • Sensitivity and Specificity
  • Slovakia / epidemiology


  • Biomarkers, Tumor
  • Genetic Markers
  • Dihydrouracil Dehydrogenase (NADP)