Pharmacogenetic Study of 5-Fluorouracil-Related Severe Toxicity in Thai Cancer Patients: A Novel SNP DetectionEkaphop Sirachainan1*, Thanyanan Reungwetwattana1, Yupin Wisetpanit1, Ravat Panvichian1, Thitiya Sirisinha1, Touch Ativitavas1, Vorachai Ratanatharathorn1, Narumol Trachu2 and Chonlaphat Sukasem3*
- *Corresponding Authors:
- Ekaphop Sirachainan
Division of Medical Oncology
Department of Medicine, Faculty of Medicine Ramathibodi Hospital
Mahidol University, Bangkok, Thailand
E-mail: [email protected]
- Chonlaphat Sukasem
Division of Pharmacogenomics and Personalized Medicine,
Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand,
E-mail: [email protected]
Received date: March 24, 2012; Accepted date: September 24, 2012; Published date: September 29, 2012
Citation: Sirachainan E, Reungwetwattana T, Wisetpanit Y, Panvichian R, Sirisinha T, et al. (2012) Pharmacogenetic Study of 5-Fluorouracil-Related Severe Toxicity in Thai Cancer Patients: A Novel SNP Detection. J Pharmacogenomics Pharmacoproteomics 3:112. doi: 10.4172/2153-0645.1000112
Copyright: © 2012 Sirachainan E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: The objective of this study is to determine the extent of (DPYD) Dihydropyrimidine Dehydrogenase Gene] polymorphisms of Thai cancer patients who received 5-FU based chemotherapy regimens.
Methods: The study was conducted a pharmacogenetic analysis to determine the polymorphisms of DPYD gene in 116. Thai cancer patients. 76 patients developed severe (grade 3-4) toxicities after receiving the first or second cycle of 5-FU based chemotherapy. The other subject group consisted of 40 patients without severe toxicity. The DNA sequencing of every amplicon was done to identify 11 mutations as reported in Asian population. The actual change of absolute neutrophil count (ANC), hematocrit, platelet and percentage of neutrophil were compared.
Results: We detected 13 SNPs of which 6 SNPs were found in exons; 967G>A, 1011A>T, 1236G>A, 1774C>T, 1896T>C and 1627A>G. The other 7 SNPs were found in intron but only IVS14+1G>A is the intron splice site. We found homozygous GG of 1627A>G in 4 patients who had severe toxicities. Statistically significant difference in actual ANC change and percentage of neutrophil change in homozygous GG [P = .011 and .009] were found. The median nadir ANC of homozygous GG is 399.6 cells/mm3. This SNP has cause the amino acid change from isoleucine to valine. Novel heterozygous SNPs (967G>A, 1774C>T) that cause the amino acid change were found in two patients with severe toxicities.
Conclusions: 1627A>G, 967G>A, 1774C>T and IVS14+G>A might be the cause of (DPD) Dihydro Pyrimidine Dehydrogenase deficiency in Thai patients. The further study needs to establish the functional DPD protein in this population. Ten novel SNPs were discovered in our study.