| Abstract |
Gemcitabine (dFdC) is a high efficacy chemotherapy drug for patients with pancreatic cancer, non-small cell lung cancer, bladder cancer, ovarian cancer and cholangiocarcinoma (bile duct cancer). However, its clinical outcome and adverse effects vary among patients, depending on the variations of gemcitabine pharmacokinetics among individuals. Gemcitabine is metabolized by cytidine deaminase (CDA) to an inactive form. Recent study reports CDA*2 79A>C (K27Q, rs2072671) mutant allele is correlated with CDA enzyme activity. Patients who carry CDA*2 genotype have higher CDA activity and lower response rate than patients with wild type CDA. Patients who carry CDA*3 208G>A (A70T, rs60369023) genotype have lower CDA activity than patients with wild type CDA, and experience a higher incidence of neutropenia. The prevalence of CDA gene variations and their enzymatic activities have not been reported in Thai populations. This study aims to determine the frequency of the two major CDA variants in sixty one Northeast Thai healthy volunteers, and to examine the correlation between CDA genotype and the enzyme activity. The CDA*2 and *3 genotypes were determined using real-time PCR technique, and the plasma CDA activity was evaluated by spectrophotometric technique. The prevalence of CDA*1/*2 was observed at 22.95%. Neither the homozygous mutant allele of CDA*2, nor any forms of CDA*3 were detected in this study. This study concludes that the allele frequency of CDA*2 in Thai population significantly differs from American (P = 0.002) and European populations (P = 0.001), but it is not different from Chinese (P = 0.828), Japanese (P = 0.114), Korean (P = 0.490) and African (P = 0.061) populations. In addition, the mean of CDA activity in CDA*1/*1 volunteers was not significantly different from CDA*1/*2 group (P = 0.08). The majority of insignificance statistics for CDA allele frequencies among populations could result from the small sample size effects. |
Publication
Journal Publication
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