The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): hematologic and evolutionary implications

Premawardhena, Anuja; Fisher, Chris; Liu, Y.T.; Verma, I. C.; Silva, S. de; Arambepola, M.; Clegg, J. B.; Weatherall, D. J.

doi:10.1016/s1079-9796(03)00071-8

Cited by 133 publications

(112 citation statements)

References 16 publications

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“…Previous study has suggested that homozygosity for the (TA)7 allele occurs in 10-25% of the populations of Africa and the Indian subcontinent, and occurs at a much lower frequency in Southeast Asia. 9 In the present study, homozygosity for the (TA)7 allele was found only in 0.78% …”

Section: Discussioncontrasting

confidence: 46%

“…7 Global studies of polymorphisms in UGT1A have shown alleles and genotypes to be unequally distributed among different ethnic human populations across the world. 4,8,9 In the present study, the intra-ethnic difference in allele and haolptype frequencies of polymorphisms in UGT1A1 was examined in three Chinese ethnic populations. In addition, the relationship between the concentrations of total serum bilirubin (T-bil) and haplotype structure of UGT1A1 in healthy people were evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations

et al. 2006

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Variants within the human UGT1A1 gene are associated with irinotecan induced severely adverse reactions and hyperbilirubinemia. Intra-ethnic differences in the genetic variation and haplotypes of UGT1A1 gene have been analyzed in the present study. Relationship between the concentrations of total serum bilirubin (T-bil) and haplotype structure of UGT1A1 in healthy people were also evaluated. We genotyped five functional polymorphisms including À3279T4G and À3156G4A in the enhancer region, (TA)647 in the TATA box, and 211G4A (G71R), 686C4A (P229Q) in the exon1 region of UGT1A1 in three groups of healthy Chinese ethnic populations, consisting of 264 subjects of She origin, 539 of Han origin and 273 of Dong origin. The distribution of À3279T4G, (TA)647, 211G4A of UGT1A1 differed greatly as between the three ethnic groups. All of six haplotypes differed considerably between at least two of the three groups, which highlighted the need to analyze clinically irinotecan toxicity relevant SNPs and haplotypes in a variety of different racial groups within the Chinese population. Total bilirubin concentration in homozygous carriers of the À3279G and (TA)7 allele were significantly higher than those in heterozygous carriers or homozygous carriers of wild-type alleles. Carriers of the variant haplotypes (À3279G; À3156A; (TA)7; 211G; 686C) had higher serum T-Bil concentrations compared with the other groups. Our results indicate that heterogeneity among different ethnic populations is possibly the result of microevolution and is relevant to studies into the effect of tailored drug treatment.

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Section: Discussioncontrasting

confidence: 46%

Section: Introductionmentioning

confidence: 99%

Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations

et al. 2006

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“…2,3 This allele (henceforth referred to as '(TA) 7 ') occurs at frequencies up to 42% in some African and South Asian populations, and is seen in Asian and European populations at lower rates (1-15%). Two other alleles, A(TA) 5 TAA and A(TA) 8 TAA, are seen almost exclusively in African populations. 4,5 This heritable variation in glucuronidation activity has also been investigated in pharmacogenetic contexts.…”

Section: Introductionmentioning

confidence: 99%

“…Two other alleles, A(TA) 5 TAA and A(TA) 8 TAA, are seen almost exclusively in African populations. 4,5 This heritable variation in glucuronidation activity has also been investigated in pharmacogenetic contexts. The active metabolite of the anti-tumor agent irinotecan, SN-38, is glucuronidated by UGT1A1 to the inactive SN-38 glucuronide, which is excreted.…”

Section: Introductionmentioning

confidence: 99%

UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia

Singer¹,

et al. 2007

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Nilotinib is a novel BCR-ABL inhibitor with significantly improved potency and selectivity over imatinib. In Phase I and Phase II clinical studies of nilotinib in patients with a variety of leukemias, infrequent instances of reversible, benign elevation of bilirubin were observed. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) glucuronidates bilirubin in humans, and a polymorphism in the promoter of the gene that encodes it has been associated with hyperbilirubinemia during treatment with a number of drugs. Pharmacogenetic analysis of that TArepeat polymorphism found an association between the (TA) 7 / (TA) 7 genotype and risk of hyperbilirubinemia in Phase I patients with imatinib-resistant/intolerant chronic myeloid leukemia (CML) or relapsed/refractory Ph þ acute lymphoblastic leukemia (ALL); this result was replicated in two separate analyses of the chronic phase (CP) and accelerated phase (AP) CML arms of a Phase II study. As nilotinib is not known to be glucuronidated by UGT1A1, the combined impact of inhibition of UGT1A1 activity by nilotinib and genetic polymorphism is the most likely cause of the increased rate of hyperbilirubinemia.

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“…Six of 81 Korean patients (7.4%) had phenotype of UGT1A1*6 homozygosity. Another phenotype associated with low tumour responses and high irinotecan-related toxicity is UGT1A1*28, and it is highly prevalent in Caucasian individuals with reported frequencies of 0.29 -0.47 (Bosma et al, 1995;Premawardhena et al, 2003), whereas it has much lower frequency in Asians (0.08 -0.19) . In Korean report, the frequency of UGT1A1*28 was 0.07 (Han et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer

Park

et al. 2006

Br J Cancer

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Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m À2 was administered on days 1 and 8 and cisplatin 60 mg m À2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0 -82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer. British Journal of Cancer (2006) (Jemal et al, 2004), and also in Korea (Shin et al, 2004). The proportion of histologic diagnosis with small-cell lung cancer (SCLC) in the United States is approximately 15% of patients with lung cancer (Jemal et al, 2004), and more than half of these patients are diagnosed with extensive-stage disease. Incidence of SCLC had paralleled trends in cigarette smoking, and smoking prevalence for the adult population is relatively high in Korea. During the last decade, most patients with extensivestage SCLC (ES-SCLC) have been treated with etoposide and platinum resulting in a median survival of 8 -10 months (Roth et al, 1992). Although several trials of platinum-based combination chemotherapy were performed, it failed to show a superiority to combination of etoposide and cisplatin (EP) (Mavroudis et al, 2001;Sundstrom et al, 2002).Irinotecan, which inhibits the function of topoisomerase I in cancer cells, demonstrated synergism and non-cross resistance when combined with platinum agents (Fukuda et al, 1996;Masuda et al, 1996). Kudoh et al (1998) reported that combination chemotherapy of irinotecan and cisplatin (IP) in patients with SCLC showed a promising response rate of 84 with 29% of complete responses and median survival over 13 months. Since then, several phase II/III trials of irinotecan-based combination chemotherapy with different dose and schedule were performed with varying results in SCLC patients (Noda et al, 2002;Kudoh et al, 2005;Hanna et al, 2006;Kinoshita et al, 2006;Schmittel et al, 2006). In...

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The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): hematologic and evolutionary implications

Cited by 133 publications

References 16 publications

Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations

Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations

UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia

Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer

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