Polymorphisms of the UDP-Glucuronosyl Transferase 1A Genes Are Associated with Adverse Events in Cancer Patients Receiving Irinotecan-Based Chemotherapy

Inoue, Ken‐ichiro; Sonobe, Momoyo; Kawamura, Yukinori; Etoh, Takashi; Takagi, Masakazu; Matsumura, Takashi; Kikuyama, Masataka; Kimura, Midori; Minami, Sato; Utsuki, Hiroaki; Yamazaki, Takeaki; Suzuki, Takeshi; Tsuji, Daiki; Hayashi, Hideki; Itoh, Ken

doi:10.1620/tjem.229.107

Cited by 36 publications

(25 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our previous study [21] revealed that the allele frequency of UGT1A9*22 in healthy Japanese volunteers was 0.66, which is comparable to that in Japanese colorectal cancer patients (0.54–0.66) [9, 33, 34]. A study of colorectal cancer patients who were mainly of Caucasian origin reported a UGT1A9*22 allele frequency of 0.4 [8, 35], which is similar to that observed here for the healthy Uzbek volunteers.…”

Section: Discussionmentioning

confidence: 87%

“…However, because the frequency of UGT1A7*4 is known to be quite rare among Caucasian [17, 36], Japanese [9, 26, 37], and Chinese [38] populations, we assumed that the only possible genotype was UGT1A7*1/*3 . Accordingly, the allele frequency of UGT1A7*1 in the Uzbek population was lower than that reported for East Asia and Japan [9, 26, 38], slightly higher than that reported for India [40], and similar to that reported for both Africa and Europe [12, 32, 41]. UGT1A7*3 is associated with reduced enzymatic activity compared with the wild-type [42], and might be related to the irinotecan toxicity in colorectal cancer patients [20, 34].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in the case of heterozygous N129K and heterozygous W208R in the same individual, the possible genotypes are UGT1A7*1/*3 and *2/*4 . However, because UGT1A7*4 is known to be quite rare in non-Uzbek populations [9, 17], the statistical analysis was performed on the assumption that all the genotypes were UGT1A7*1/*3 .…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Differences in UGT1A1, UGT1A7, and UGT1A9 Polymorphisms between Uzbek and Japanese Populations

et al. 2014

View full text Add to dashboard Cite

Background and ObjectivesUridine-diphosphate glucuronosyltransferase 1A (UGT1A) is a key enzyme involved in irinotecan metabolism, and polymorphisms in the UGT1A gene are associated with irinotecan-induced toxicity. The aim of this study was to elucidate the allele frequencies of UGT1A polymorphisms in healthy Uzbek volunteers, and to compare them with those of the Japanese population.MethodA total of 97 healthy volunteers from Uzbekistan were enrolled and blood samples were collected from each participant. Genotyping analysis was performed by fragment size analysis for UGT1A1*28, direct sequencing for UGT1A7*3 and UGT1A9*22, and TaqMan assays for UGT1A1*93, UGT1A1*6, UGT1A1*27, UGT1A1*60, and UGT1A7*12. The frequencies of polymorphisms were compared with the Japanese population by using the data previously reported from our study group.ResultsWhen the Uzbek and Japanese populations were compared, heterozygotes or homozygotes for UGT1A1*28, UGT1A1*60, and UGT1A1*93 were significantly more frequent in the Uzbek population (P < 0.01). The rate of UGT1A7*12 was not significantly different between the two populations, whereas UGT1A1*6 and UGT1A9*22 were significantly less frequent in the Uzbek population (P < 0.05). UGT1A7*1 were less prevalent in the Uzbek population than in the Japanese population (P < 0.01).ConclusionThe Uzbek population has different frequencies of polymorphisms in UGT1A genes compared with the Japanese population. A comprehensive study of the influence of UGT1A1 polymorphisms on the risk of irinotecan-induced toxicity is necessary for optimal use of irinotecan treatment.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differences in UGT1A1, UGT1A7, and UGT1A9 Polymorphisms between Uzbek and Japanese Populations

et al. 2014

View full text Add to dashboard Cite

show abstract

“…UGT1A1 * 28 polymorphism (rs8175347), the most commonly identified mutation, contains seven TA repeats in the promoter region [A(TA)7TAA] [8]. The frequency of UGT1A1 * 28 is high in Caucasians (about 39%) and is considered as a major predictive pharmacogenetic marker of severe hematological toxicity [9,10]. Previous studies reported that the polymorphism of UGT1A1 * 28 is associated with irinotecan-induced severe neutropenia [11,12].…”

Section: Introductionmentioning

confidence: 99%

Correlation of UGT1A1 * 28 and * 6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients

Atasilp

Chansriwong

Sirachainan

et al. 2016

Drug Metabolism and Pharmacokinetics

View full text Add to dashboard Cite

“…Single nucleotide polymorphisms for the TATA box of the promoter (UGT1A1*28, 6TAA/7TAA) and exon 1 (−211 G/A) were simultaneously determined with the PCR primer sequences as follows: 5’-ATTAACTTGGTGTATCGATTGG-3’ and 5’-AAGCATAGCAGAGTCCTTTTTTA-3’[25], while the PCR primer sequences for the phenobarbital responsive enhancer module region of the promoter (−3156 G/A) were 5’-CTGGGGATAAACATGGGATG-3’ and 5’- CACCACCACTTCTGGAACCT-3’ [26]. Direct sequencing was performed using the ABIPRISM310 Genetic Analyzer (Applied Biosystems, Foster City, CA) according to standard protocols.…”

Section: Methodsmentioning

confidence: 99%

Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer

et al. 2017

View full text Add to dashboard Cite

BackgroundIndividualized therapeutic regimen is a recently intensively pursued approach for targeting diseases, in which the search for biomarkers was considered the first and most important. Thus, the goal of this study was to investigate whether the UGT1A1, ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A genes are underlying biomarkers for gastric cancer, which, to our knowledge, has not been performed.MethodsNinety-eight tissue specimens were collected from gastric cancer patients between May 2012 and March 2015. A multiplex branched DNA liquidchip technology was used for measuring the mRNA expressions of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A. Direct sequencing was performed for determination of UGT1A1 polymorphisms. Furthermore, correlations between gene expressions, polymorphisms and clinicopathological characteristics were investigated.ResultsThe expressions of TYMS, TUBB3 and STMN1 were significantly associated with the clinicopathological characteristics of age, gender and family history of gastric cancer, but not with differentiation, growth patterns, metastasis and TNM staging in patients with gastric cancer. No clinical characteristics were correlated with the expressions of ERCC1, BRCA1, RRM1 and TOP2A. Additionally, patients carrying G allele at −211 of UGT1A1 were predisposed to developing tubular adenocarcinoma, while individuals carrying 6TAA or G allele respectively at *28 or −3156 of UGT1A1 tended to have a local invasion.ConclusionsThe UGT1A1 polymorphism may be useful to screen the risk population of gastric cancer, while TYMS, TUBB3 and STMN1 may be potential biomarkers for prognosis and chemotherapy guidance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-016-0561-x) contains supplementary material, which is available to authorized users.

show abstract

Polymorphisms of the UDP-Glucuronosyl Transferase 1A Genes Are Associated with Adverse Events in Cancer Patients Receiving Irinotecan-Based Chemotherapy

Cited by 36 publications

References 25 publications

Differences in UGT1A1, UGT1A7, and UGT1A9 Polymorphisms between Uzbek and Japanese Populations

Differences in UGT1A1, UGT1A7, and UGT1A9 Polymorphisms between Uzbek and Japanese Populations

Correlation of UGT1A1 * 28 and * 6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients

Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer

Contact Info

Product

Resources

About