Arijana, I Gusti Kamasan Nyoman and Jamal, A. Rahman A. and Suharti, Catharina (2011) ANALYSIS OF DPYD GENE IN PATIENTS WITH SOLID TUMOR WHO WERE TREATED BY 5-FU : A Cross-sectional Study of DPYD Gene in Malaysian Population. Masters thesis, Universitas Diponegoro.

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Abstract

Background: Drug adverse effects contribute to more than 100,000 deaths in the United States each year besides being the fourth leading cause of death following heart diseases, cancer, and stroke. One of the drugs that account for drug adverse
effects is 5-FU which was catabolized around 80% in the liver by DPD enzyme that encoded by DPYD gene. Variations in DPYD gene has lead to adverse effects based on several studies. Although population studies on DPYD gene have been carried out in Caucasian, African, Asian population, additional study is needed to identify distribution of DPYD gene variants in Malaysian population. The aim of this study is to analyze DPYD gene variants in Malaysian solid tumor patients who were treated with 5-FU. Methods: Blood samples from 24 Malaysian 5-FU solid tumor patients, specifically Malay and Chinese were consecutively collected. The 10 exons which were represented the most common variants of DPYD gene in the world were
chosen from literature review. The amplification of 10 exon and its flanking regions of DPYD gene was performed using PCR. Sanger sequencing was performed for reading the sequence.
Results: The study revealed variations of c.85T>C in exon 2, c.496A>G in exon 6, c.1627 A>G in exon 13; IVS13+39 C>T in intron 13; IVS13+40 A>G in intron 13, c.1896 T>C in exon 14, c.2194 G>A in exon 18, IVS22+55 C>T in intron 22; IVS22+65 C>T in intron 22 with allelic frequency 10.42%, 4.17%, 31.25%,
27.08%, 64.58%, 8.33%, 4.17%, 100%, 2.08% respectively. New unreported heterozygous IVS22+65 C>T in intron 22 was found in 1 Chinese patient. Conclusions: Distribution of DPYD variants in Malaysian population specifically Malay and Chinese had specific pattern.
Keywords: 5-FU, DPYD gene, DPYD variants, Malaysian population.

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