Role of UGT1A1*6 in irinogenetics in Asians

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.