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

a technology of irinotecan and side effects, which is applied in the field of assisting prediction of the risk of occurrence of the side effect of irinotecan, can solve problems such as reported effects

Inactive Publication Date: 2018-08-23
YAMAGUCHI UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention helps predict the risk of side effects from anti-cancer drug irinotecan and can help treat each patient with a personalized medicine approach. This can improve the chances of effective treatment for cancer.

Problems solved by technology

However, several serious side effects have been reported, including leucopenia, neutropenia, and diarrhea.

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

example 1

[Search for an Irinotecan-Side-Effect-Related Factor]

[0092]A serious side effect of irinotecan can be sometimes observed even in patients without any UGT1A gene polymorphism (at 7 sites including UGT1A1*6, *27, *28, UGT1A7 (387T>G, 622T>C), UGT1A9*1b, UGT1A1*60) related to the side effect. Here, the following method was used to search for a novel irinotecan-side-effect-related factor.

(Subjects Analyzed)

[0093]A next-generation sequencer was used to perform exome analysis by using genomic DNA prepared from peripheral blood of: a case group (Group 1; n=5), as a control group, in which all the above-mentioned 7 different polymorphisms were genotypes having a low risk of the side effect and no side effect was observed; a case group (Group 2; n=5) in which all the 7 different polymorphisms of the above UGT1A gene were genotypes having a low risk of the side effect, but the side effect (Grade 3: leucopenia, neutropenia) was observed; and a case group (Group 3; n=5) being heterozygous for a...

example 2

[Examining Results of Exome Analysis]

(Methodology for Examining Results of Exome Analysis)

[0098]By using a TaqMan® probe method, clinical samples from 75 Japanese patients with colon cancer who had received irinotecan were further examined with respect to: among the candidates for irinotecan-side-effect-related factor as obtained from the results of Example 1, a single nucleotide polymorphism rs1980576 in a region encoding the APCDD1L gene; a single nucleotide polymorphism rs2272761 in a region encoding the R3HCC1 gene; a single nucleotide polymorphism rs12577167 in a region encoding the OR5112 gene; a single nucleotide polymorphism rs1547 in a region encoding the MKKS gene; a single nucleotide polymorphism rs9425343 in a region encoding the EDEM3 gene; a single nucleotide polymorphism rs7265854 in a region encoding the APCDD1L gene; and a single nucleotide polymorphism rs1135640 in a region encoding the ACOX1 gene. By using TaqMan SNP Assays Human (manufactured by Applied Biosystem...

example 3

[Linkage to UGT1A Gene Mutations]

[0100]Regarding the 74 cases in Example 2, the TaqMan probe method and direct sequencing were used to determine the genotype of each of the UGT genes, namely UGT1A gene polymorphisms including UGT1A9*1b, UGT1A7 [387], UGT1A7 [622], UGT1A1*60, UGT1A1*28, UGT1A1*6 and UGT1A1*27, as well as to determine the genotype of rs9425343, rs2272761, rs12577167, rs1135640, rs1547, rs7265854, or rs1980576. Further, linkage disequilibrium analysis and LD analysis were conducted using Haploview 4.2 software. The results are shown in FIG. 10. In FIG. 10, the numbers indicate correlation coefficients (r2). As shown in FIG. 10, the UGT1A gene polymorphisms were not linked to (associated with) rs9425343, rs2272761, rs12577167, rs1135640, rs1547, rs7265854, or rs1980576. In addition, no linkage was observed among rs9425343, rs2272761, rs12577167, rs1135640, rs1547, rs7265854, and rs1980576. This clearly demonstrated that these single nucleotide polymorphisms (marker site...

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Abstract

An object of the present invention is to provide a simple and efficient device for predicting a 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 the 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 OR5112 gene, the MKKS gene, the EDEM3 gene, or the ACOX1 gene which are present on genomic DNA in a biological sample collected from a test subject; or a single nucleotide polymorphism which is in linkage disequilibrium with or genetically linked to the single nucleotide polymorphism, and determining whether the single nucleotide polymorphism is homozygous for a variant type, heterozygous, or homozygous for a wild-type.

Description

TECHNICAL FIELD[0001]The present invention relates to a method for assisting a prediction of a risk of occurrence of a side effect of irinotecan, and to a probe or primer for use in analyzing single nucleotide polymorphisms in the method.BACKGROUND ART[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 which is synthesized from camptothecin, a Camptotheca-derived anti-tumor alkaloid, and has been known to be useful in treating cancer such as lung cancer and metastatic colon cancer. Irinotecan inhibits the activity of a topoisomerase, an enzyme that promotes DNA replication, thereby exhibiting a potent anti-cancer effect. However, several serious side effects have been reported, including leucopenia, neutropenia, and diarrhea.[0003]Recently, personalized medicine (i.e., individualized medicine), in which an optimal...

Claims

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Application Information

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IPC IPC(8): C12Q1/6827C12Q1/6809C12Q1/6876G01N33/50
CPCC12Q1/6827C12Q1/6809C12Q1/6876G01N33/5014C12Q2600/158C12Q2600/156C12Q2600/118C12Q2600/106C12Q2600/142C12Q1/6886C12Q1/68
Inventor OKA, MASAAKIHAZAMA, SHOICHITSUNEDOMI, RYOUICHI
Owner YAMAGUCHI UNIV
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