Method for assisting prediction of risk of occurrence of side effect of irinotecan

一种伊立替康、副作用的技术，应用在辅助对伊立替康副作用的发生风险的预测领域

Active Publication Date: 2017-09-26
YAMAGUCHI UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] However, the current situation is that in patients who are not considered high-risk based on the UGT1A gene polymorphism, such as patients in whom any one of UGT1A*28, UGT1A*6 is mutated or both are heterozygous , about 43% of patients were observed side effects caused by irinotecan, and thus have been looking for a new method to assist in the prediction of the risk of side effects of irinotecan

Method used

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  • Method for assisting prediction of risk of occurrence of side effect of irinotecan
  • Method for assisting prediction of risk of occurrence of side effect of irinotecan
  • Method for assisting prediction of risk of occurrence of side effect of irinotecan

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0097] [Exploration of related factors of irinotecan side effects]

[0098] Even in patients whose UGT1A gene does not have any side effects-related polymorphisms (UGT1A1*6, *27, *28, UGT1A7 (387T>G, 622T>C), UGT1A9*1b, UGT1A1*60 these 7 places), Serious side effects of irinotecan are often observed. Therefore, the new irinotecan side effects related factors were explored by the following methods.

[0099] (analysis object)

[0100] The next generation sequencer was used to perform exome analysis using genomic DNA prepared from the peripheral blood of the following group: the control group, that is, the 7 polymorphisms mentioned above were all genotypes with low risk of side effects and no side effects were confirmed Case group (group 1: n=5); case group, that is, the 7 polymorphisms of the UGT1A gene mentioned above are all genotypes with low side effects risk, but side effects are still confirmed (Grade): The case group of leukopenia, neutropenia) (group 2: n=5), has a heterozyg...

Embodiment 2

[0110] [Verification of Exome Analysis Results]

[0111] (Verification method of exome analysis results)

[0112] Among the alternative side effects factors of irinotecan obtained from the results of Example 1, the single nucleotide polymorphism rs1980576 in the region encoding the APCDD1L gene and the single nucleotide polymorphism rs2272761 in the region encoding the R3HCC1 gene The single nucleotide polymorphism rs12577167 in the region encoding the OR51I2 gene, the single nucleotide polymorphism rs1547 in the region encoding the MKKS gene, the single nucleotide polymorphism rs9425343 in the region encoding the EDEM3 gene, and the region encoding the APCDD1L gene The single nucleotide polymorphism rs7265854 in the region encoding the ACOX1 gene, the single nucleotide polymorphism rs1135640 in the region encoding the ACOX1 gene, and the TaqMan (registered trademark) probe method were further used in 75 cases of colorectal cancer patients administered irinotecan (Japan Human) cli...

Embodiment 3

[0116] [Link with UGT1A gene mutation]

[0117] For 74 cases in Example 2, for rs9425343, rs2272761, rs12577167, rs1135640, rs1547, rs7265854, rs1980576, UGT1A9*1b, UGT1A7[387], UGT1A7[622], UGT1A1*60, UGT1A1* as mutations in the UGT1A gene 28. UGT1A1*6 or UGT1A1*27, using TaqMan probe method and direct sequencing method to determine the genotype of each UGT gene, and then using Haploview4.2 software to implement linkage disequilibrium analysis and LD analysis. Show the result in Picture 10 . Picture 10 Where the value is the correlation coefficient (r 2 ). Such as Picture 10 As shown, for rs9425343, rs2272761, rs12577167, rs1135640, rs1547, rs7265854, and rs1980576, no linkage (correlation) with the UGT1A gene mutation was confirmed. In addition, no linkage has been confirmed between rs9425343, rs2272761, rs12577167, rs1135640, rs1547, rs7265854, and rs1980576. It can be seen that these single nucleotide polymorphisms (label sites) can complementarily be used to assist irino...

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Abstract

The present invention addresses the problem of providing a simple and efficient means for predicting the risk of occurrence of a side effect of irinotecan by analyzing a single nucleotide polymorphism in a region encoding a specific gene. The prediction of the risk of occurrence of a side effect of irinotecan is assisted by analyzing: a single nucleotide polymorphism in a region encoding the APCDD1L gene, the R3HCC1 gene, the OR51I2 gene, the MKKS gene, the EDEM3 gene, or the ACOX1 gene which are present on genomic DNA in a biological sample collected from a subject; or a single nucleotide polymorphism which is in linkage disequilibrium with or genetically linked to the single nucleotide polymorphism, thereby determining whether the single nucleotide polymorphism is homozygous or heterozygous for a variant-type, or homozygous for a wild-type and assisting prediction of the risk of occurrence of a side effect of irinotecan.

Description

Technical field [0001] The present invention relates to a method for assisting in predicting the risk of occurrence of side effects of irinotecan, and a probe or primer used for the analysis of single nucleotide polymorphism in the method. Background technique [0002] Irinotecan (CPT-11: 1,4'-Bipiperidine-1'-carboxylic acid (S)-4,11-diethyl-3,4,12,14-tetrahydro-4-hydroxy-3, 14-Dioxo-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl ester (CAS NO: 97682-44-5) ) Is an anticancer agent synthesized from camptothecin, an antitumor alkaloid derived from Camptotheca acuminata, and is known to be useful in treating cancers such as lung cancer and metastatic colorectal cancer. Irinotecan exhibits an excellent anticancer effect by inhibiting topoisomerase, an enzyme that promotes DNA replication. However, severe side effects such as leukopenia, neutropenia, and diarrhea have been reported. [0003] In recent years, customized medical care, that is, personalized medical care, which plans...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68C12N15/09
CPCC12Q1/6886C12Q2600/106C12Q2600/142C12Q2600/156C12Q1/68C12Q1/6809C12Q1/6827C12Q1/6876C12Q2600/118C12Q2600/158G01N33/5014
Inventor 冈正朗硲彰一恒富亮一
Owner YAMAGUCHI UNIV
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