Evaluation of: Jada SR, Lim R, Wong CI et al.: Role ofUGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A polymorphisms in irinotecan-induced neutropenia in Asian cancer patients. Cancer Sci. 98(9), 1461-1467 (2007). The pharmacokinetics and toxicity of irinotecan vary widely among patients. This review focuses primarily on a study of the role of UGT1A1*6, UGT1A1*28, and ABCG2 421C>A in three Asian cancer patient populations treated with a 3-weekly regimen of irinotecan. In that study, a statistically significantly higher level of SN-38 and a relatively lower degree of glucuronidation occurred in patients with the UGT1A1*6 homozygote genotype than in patients with the reference genotype. The UGT1A1*6 allele was associated with an increased risk of severe neutropenia. In addition, the study of gene allele frequencies in three healthy Asian populations indicated that the allelic frequency of UGT1A1*6 was higher in the healthy Chinese subjects than in the Malaysian or Indian subjects. UGT1A1*28 and ABCG2 421C>A were not associated with the pharmacokinetics of SN-38 or the severity of neutropenia. In this evaluation, we put this study into the context of similar studies of irinogenetics (irinotecan pharmacogenetics) in Asians and discuss the application of UGT1A1 testing in Asian cancer patients treated with irinotecan-containing regimens.
Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.