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

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.

1 - 7 . (canceled) 
     
     
         8 . A method for assisting a prediction of a risk of occurrence of a side effect of irinotecan, comprising
 analyzing a single nucleotide polymorphism in a region encoding APCDD1L gene, R3HCC1 gene, MKKS gene, EDEM3 gene, or ACOX1 gene which is present on genomic DNA in a biological sample collected from a test subject, wherein the single nucleotide polymorphism is any one of the following (a), (b), (d), (e) and (g), and   determining whether the single nucleotide polymorphism is homozygous for a variant type, homozygous for a wild-type, or heterozygous:   (a) a single nucleotide polymorphism present at nucleotide 186 of the nucleotide sequence encoding the APCDD1L gene and set forth in SEQ ID NO: 1 or a complementary sequence thereof;   (b) a single nucleotide polymorphism present at nucleotide 358 of the nucleotide sequence encoding the R3HCC1 gene and set forth in SEQ ID NO: 2 or a complementary sequence thereof;   (d) a single nucleotide polymorphism present at nucleotide 1549 of the nucleotide sequence encoding the MKKS gene and set forth in SEQ ID NO: 4 or a complementary sequence thereof;   (e) a single nucleotide polymorphism present at nucleotide 2459 of the nucleotide sequence encoding the EDEM3 gene and set forth in SEQ ID NO: 5 or a complementary sequence thereof; and   (g) a single nucleotide polymorphism present at nucleotide 936 of the nucleotide sequence encoding the ACOX1 gene and set forth in SEQ ID NO: 6 or a complementary sequence thereof.   
     
     
         9 . The method according to  claim 8 , comprising assisting to predict that the risk of occurrence of a side effect of irinotecan is high, when the single nucleotide polymorphism is homozygous for a variant type with respect to the single nucleotide polymorphism set forth in (a), or when the single nucleotide polymorphism is homozygous for a wild-type with respect to the single nucleotide polymorphism set forth in (g), and assisting to predict the risk of occurrence of a side effect of irinotecan is low, when the single nucleotide polymorphism is homozygous for a wild-type with respect to the single nucleotide polymorphism set forth in (b) or (d), or when the single nucleotide polymorphism is homozygous for a wild-type with respect to the single nucleotide polymorphism set forth in (e). 
     
     
         10 . The method according to  claim 8 , comprising analyzing a single nucleotide polymorphism in a region encoding APCDD1L gene, or R3HCC1 gene, wherein the single nucleotide polymorphism is the following (a) or (b):
 (a) a single nucleotide polymorphism present at nucleotide 186 of the nucleotide sequence encoding the APCDD1L gene and set forth in SEQ ID NO: 1 or a complementary sequence thereof;   (b) a single nucleotide polymorphism present at nucleotide 358 of the nucleotide sequence encoding the R3HCC1 gene and set forth in SEQ ID NO: 2 or a complementary sequence thereof.   
     
     
         11 . The method according to  claim 10 , comprising assisting to predict that the risk of occurrence of a side effect of irinotecan is high, when the single nucleotide polymorphism is homozygous for a variant type with respect to the single nucleotide polymorphism set forth in (a), and assisting to predict the risk of occurrence of a side effect of irinotecan is low, when the single nucleotide polymorphism is homozygous for a wild-type with respect to the single nucleotide polymorphism set forth in (b). 
     
     
         12 . The method according to  claim 8 , comprising analyzing a single nucleotide polymorphism in a region encoding R3HCC1 gene, wherein the single nucleotide polymorphism is the following (b):
 (b) a single nucleotide polymorphism present at nucleotide 358 of the nucleotide sequence encoding the R3HCC1 gene and set forth in SEQ ID NO: 2 or a complementary sequence thereof.   
     
     
         13 . The method according to  claim 12 , comprising assisting to predict the risk of occurrence of a side effect of irinotecan is low, when the single nucleotide polymorphism is homozygous for a wild-type with respect to the single nucleotide polymorphism set forth in (b). 
     
     
         14 . The method according to  claim 8 , wherein the side effect is leucopenia or neutropenia. 
     
     
         15 . A probe for use in analyzing a single nucleotide polymorphism in the method according to  claim 8 , which is any one of the following (h), (i), (k), (l), and (n):
 (h) a probe consisting of an oligonucleotide that hybridizes, under a stringent condition, with a sequence of 5 to 50 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 186 of the nucleotide sequence encoding APCDD1L gene and set forth in SEQ ID NO: 1 or a complementary sequence thereof;   (i) a probe consisting of an oligonucleotide that hybridizes, under a stringent condition, with a sequence of 5 to 50 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 358 of the nucleotide sequence encoding R3HCC1 gene and set forth in SEQ ID NO: 2 or a complementary sequence thereof;   (k) a probe consisting of an oligonucleotide that hybridizes, under a stringent condition, with a sequence of 5 to 50 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 1549 of the nucleotide sequence encoding MKKS gene and set forth in SEQ ID NO: 4 or a complementary sequence thereof;   (l) a probe consisting of an oligonucleotide that hybridizes, under a stringent condition, with a sequence of 5 to 50 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 2459 of the nucleotide sequence encoding EDEM3 gene and set forth in SEQ ID NO: 5 or a complementary sequence thereof; and   (n) a probe consisting of an oligonucleotide that hybridizes, under a stringent condition, with a sequence of 5 to 50 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 936 of the nucleotide sequence encoding ACOX1 gene and set forth in SEQ ID NO: 6 or a complementary sequence thereof.   
     
     
         16 . A primer for use in analyzing a single nucleotide polymorphism in the method according to  claim 8 , which is any one of the following (o), (p), (r), (s) and (u):
 (o) a primer consisting of an oligonucleotide that can amplify at least 5 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 186 of the nucleotide sequence encoding APCDD1L gene and set forth in SEQ ID NO: 1;   (p) a primer consisting of an oligonucleotide that can amplify at least 5 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 358 of the nucleotide sequence encoding R3HCC1 gene and set forth in SEQ ID NO: 2;   (r) a primer consisting of an oligonucleotide that can amplify at least 5 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 1549 of the nucleotide sequence encoding MKKS gene and set forth in SEQ ID NO: 4;   (s) a primer consisting of an oligonucleotide that can amplify at least 5 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 2459 of the nucleotide sequence encoding EDEM3 gene and set forth in SEQ ID NO: 5; and   (u) a primer consisting of an oligonucleotide that can amplify at least 5 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 936 of the nucleotide sequence encoding ACOX1 gene and set forth in SEQ ID NO: 6.   
     
     
         17 . A kit for assisting a prediction of a risk of occurrence of a side effect of irinotecan, comprising the probe according to  claim 15 . 
     
     
         18 . A kit for assisting a prediction of a risk of occurrence of a side effect of irinotecan, comprising the primer according to  claim 16 . 
     
     
         19 . The method according to  claim 9 , wherein the side effect is leucopenia or neutropenia. 
     
     
         20 . The method according to  claim 10 , wherein the side effect is leucopenia or neutropenia. 
     
     
         21 . The method according to  claim 11 , wherein the side effect is leucopenia or neutropenia. 
     
     
         22 . The method according to  claim 12 , wherein the side effect is leucopenia or neutropenia. 
     
     
         23 . The method according to  claim 13 , wherein the side effect is leucopenia or neutropenia. 
     
     
         24 . A probe for use in analyzing a single nucleotide polymorphism in the method according to  claim 9 , which is any one of the following (h), (i), (k), (l), and (n):
 (h) a probe consisting of an oligonucleotide that hybridizes, under a stringent condition, with a sequence of 5 to 50 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 186 of the nucleotide sequence encoding APCDD1L gene and set forth in SEQ ID NO: 1 or a complementary sequence thereof;   (i) a probe consisting of an oligonucleotide that hybridizes, under a stringent condition, with a sequence of 5 to 50 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 358 of the nucleotide sequence encoding R3HCC1 gene and set forth in SEQ ID NO: 2 or a complementary sequence thereof;   (k) a probe consisting of an oligonucleotide that hybridizes, under a stringent condition, with a sequence of 5 to 50 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 1549 of the nucleotide sequence encoding MKKS gene and set forth in SEQ ID NO: 4 or a complementary sequence thereof;   (l) a probe consisting of an oligonucleotide that hybridizes, under a stringent condition, with a sequence of 5 to 50 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 2459 of the nucleotide sequence encoding EDEM3 gene and set forth in SEQ ID NO: 5 or a complementary sequence thereof; and   (n) a probe consisting of an oligonucleotide that hybridizes, under a stringent condition, with a sequence of 5 to 50 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 936 of the nucleotide sequence encoding ACOX1 gene and set forth in SEQ ID NO: 6 or a complementary sequence thereof.   
     
     
         25 . A primer for use in analyzing a single nucleotide polymorphism in the method according to  claim 9 , which is any one of the following (o), (p), (r), (s) and (u):
 (o) a primer consisting of an oligonucleotide that can amplify at least 5 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 186 of the nucleotide sequence encoding APCDD1L gene and set forth in SEQ ID NO: 1;   (p) a primer consisting of an oligonucleotide that can amplify at least 5 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 358 of the nucleotide sequence encoding R3HCC1 gene and set forth in SEQ ID NO: 2;   (r) a primer consisting of an oligonucleotide that can amplify at least 5 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 1549 of the nucleotide sequence encoding MKKS gene and set forth in SEQ ID NO: 4;   (s) a primer consisting of an oligonucleotide that can amplify at least 5 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 2459 of the nucleotide sequence encoding EDEM3 gene and set forth in SEQ ID NO: 5; and   (u) a primer consisting of an oligonucleotide that can amplify at least 5 consecutive nucleotides containing a single nucleotide polymorphism site present at nucleotide 936 of the nucleotide sequence encoding ACOX1 gene and set forth in SEQ ID NO: 6.   
     
     
         26 . A kit for assisting a prediction of a risk of occurrence of a side effect of irinotecan, comprising the probe according to  claim 24 . 
     
     
         27 . A kit for assisting a prediction of a risk of occurrence of a side effect of irinotecan, comprising the primer according to  claim 25 .