Influence of drug transporters polymorphisms on severe adverse reaction caused by irinotecan in colorectal cancer patients

doi:10.3877/cma.j.issn.2095-3224.2018.03.012

Abstract

Abstract:

Objective

To investigate the influence of drug transporters (ABCB1-3435C>T and ABCC2-24C>T) polymorphisms on severe adverse reaction (mainly refers to grade 3~4 delayed diarrhea and neutropenia) caused by irinotecan in colorectal cancer patients.

Methods

A total of 91 colorectal cancer patients from Zhengzhou Central Hospital Affiliated to Zhengzhou University were enrolled in this study. Peripheral venous blood were collected. The genetic polymorphisms of ABCB1-3435C>T and ABCC2-24C>T were analyzed by PCR-Sanger sequence. The adverse reaction during chemotherapy were observed and recorded. The differences of the incidence of grade 3~4 adverse reaction were compared in patients with different genotypes.

Results

There is effect of ABCC2-24C>T polymorphisms on severe delayed diarrhea (χ²=5.067, P=0.024) but not neutropenia (χ²=3.107, P=0.078) in colorectal cancer patients. However, ABCB1-3435C>T polymorphisms don′t affect the severe adverse reaction caused by irinotecan (χ²=0.237, χ²=2.139, all P>0.05).

Conclusion

ABCC2-24C>T but not ABCB1-3435C>T mutation is related to severe toxicity caused by irinotecan in colorectal cancer patients. It can reduce severe adverse reaction that detecting ABCC2-24C>T mutation before using irinotecan.

Key words: Colorectal neoplasms, Drug transporters, Genetic polymorphisms, Irinotecan, Adverse reaction

Chao Ma, Yan Jin, Xibin Duan, Wei Cao, Guochen Xing, Shanyong Yi, Xuemin Li, Xiaofei Wang. Influence of drug transporters polymorphisms on severe adverse reaction caused by irinotecan in colorectal cancer patients[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2018, 07(03): 257-261.

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References 21

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基因型	例数	频率（%）	等位基因频率
ABCB1-3435C>T	?	?	C	T
CC	44	48.3	0.67	0.33
CT	34	37.4	?	?
TT	13	14.3	?	?
ABCC2-24C>T	?	?	C	T
CC	65	71.4	0.84	0.16
CT	23	25.3	?	?
TT	3	3.3	?	?

基因型	例数	频率（%）	等位基因频率
ABCB1-3435C>T	?	?	C	T
CC	44	48.3	0.67	0.33
CT	34	37.4	?	?
TT	13	14.3	?	?
ABCC2-24C>T	?	?	C	T
CC	65	71.4	0.84	0.16
CT	23	25.3	?	?
TT	3	3.3	?	?

基因型	ABCB1-3435C>T			ABCC2 -24C>T			是否首次使用伊立替康
基因型	CC（n=44）	CT（n=34）	TT（n=13）	CC（n=65）	CT（n=23）	TT（n=3）	是	否
迟发性腹泻（%）	6（13.6）	6（17.6）	2（15.4）	6（9.2）	7（30.4）	1（33.3）	9（18.0）	5（12.2）
χ²值	?	?	0.237	?	?	5.067	?	0.583
P值	?	?	0.888^#	?	?	0.024^#	?	0.445
中性粒细胞减少（%）	14（31.8）	16（47.1）	6（46.2）	22（33.8）	12（52.2）	2（66.7）	21（42.0）	15（36.6）
χ²值	?	?	2.139	?	?	3.107	?	0.276
P值	?	?	0.343^#	?	?	0.078^#	?	0.559

基因型	ABCB1-3435C>T			ABCC2 -24C>T			是否首次使用伊立替康
基因型	CC（n=44）	CT（n=34）	TT（n=13）	CC（n=65）	CT（n=23）	TT（n=3）	是	否
迟发性腹泻（%）	6（13.6）	6（17.6）	2（15.4）	6（9.2）	7（30.4）	1（33.3）	9（18.0）	5（12.2）
χ²值	?	?	0.237	?	?	5.067	?	0.583
P值	?	?	0.888^#	?	?	0.024^#	?	0.445
中性粒细胞减少（%）	14（31.8）	16（47.1）	6（46.2）	22（33.8）	12（52.2）	2（66.7）	21（42.0）	15（36.6）
χ²值	?	?	2.139	?	?	3.107	?	0.276
P值	?	?	0.343^#	?	?	0.078^#	?	0.559

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