Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan

Janelle M. Hoskins; Gary L. Rosner; Mark J. Ratain; Howard L. McLeod; Federico Innocenti

doi:10.2217/pgs.09.35

Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan

Janelle M. Hoskins, Gary L. Rosner, Mark J. Ratain, Howard L. McLeod, Federico Innocenti

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Aims: A recent study found that variation in camptothecin pharmacodynamic genes (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in irinotecan-treated cancer patients (median dose: 180 mg/m ²), which suggests that these genes might predict outcomes to irinotecan-based therapies. The present study was conducted to evaluate previous gene associations using an independent sample of patients receiving irinotecan. Materials & methods: DNA was isolated from 85 advanced cancer patients treated with 300 or 350 mg/m² irinotecan and genotyped for haplotype-tag polymorphisms across TOP1, PARP1, TDP1 and XRCC1. Associations between genotypes and haplotypes and log(absolute neutrophil count nadirs) were assessed by linear regression. Results: No associations were observed. Conclusion: Our findings suggest that the genes we tested do not influence toxicity of irinotecan when adminstered at 300-350 mg/m².

Original language	English (US)
Pages (from-to)	1139-1146
Number of pages	8
Journal	Pharmacogenomics
Volume	10
Issue number	7
DOIs	https://doi.org/10.2217/pgs.09.35
State	Published - Jul 2009
Externally published	Yes

Keywords

Irinotecan
PARP1
Pharmacogenetics
TDP1
TOP1
XRCC1

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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10.2217/pgs.09.35

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title = "Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan",

abstract = "Aims: A recent study found that variation in camptothecin pharmacodynamic genes (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in irinotecan-treated cancer patients (median dose: 180 mg/m 2), which suggests that these genes might predict outcomes to irinotecan-based therapies. The present study was conducted to evaluate previous gene associations using an independent sample of patients receiving irinotecan. Materials & methods: DNA was isolated from 85 advanced cancer patients treated with 300 or 350 mg/m2 irinotecan and genotyped for haplotype-tag polymorphisms across TOP1, PARP1, TDP1 and XRCC1. Associations between genotypes and haplotypes and log(absolute neutrophil count nadirs) were assessed by linear regression. Results: No associations were observed. Conclusion: Our findings suggest that the genes we tested do not influence toxicity of irinotecan when adminstered at 300-350 mg/m2.",

keywords = "Irinotecan, PARP1, Pharmacogenetics, TDP1, TOP1, XRCC1",

author = "Hoskins, {Janelle M.} and Rosner, {Gary L.} and Ratain, {Mark J.} and McLeod, {Howard L.} and Federico Innocenti",

year = "2009",

month = jul,

doi = "10.2217/pgs.09.35",

language = "English (US)",

volume = "10",

pages = "1139--1146",

journal = "Pharmacogenomics",

issn = "1462-2416",

publisher = "Future Medicine Ltd.",

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AU - Hoskins, Janelle M.

AU - Rosner, Gary L.

AU - Ratain, Mark J.

AU - McLeod, Howard L.

AU - Innocenti, Federico

PY - 2009/7

Y1 - 2009/7

N2 - Aims: A recent study found that variation in camptothecin pharmacodynamic genes (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in irinotecan-treated cancer patients (median dose: 180 mg/m 2), which suggests that these genes might predict outcomes to irinotecan-based therapies. The present study was conducted to evaluate previous gene associations using an independent sample of patients receiving irinotecan. Materials & methods: DNA was isolated from 85 advanced cancer patients treated with 300 or 350 mg/m2 irinotecan and genotyped for haplotype-tag polymorphisms across TOP1, PARP1, TDP1 and XRCC1. Associations between genotypes and haplotypes and log(absolute neutrophil count nadirs) were assessed by linear regression. Results: No associations were observed. Conclusion: Our findings suggest that the genes we tested do not influence toxicity of irinotecan when adminstered at 300-350 mg/m2.

AB - Aims: A recent study found that variation in camptothecin pharmacodynamic genes (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in irinotecan-treated cancer patients (median dose: 180 mg/m 2), which suggests that these genes might predict outcomes to irinotecan-based therapies. The present study was conducted to evaluate previous gene associations using an independent sample of patients receiving irinotecan. Materials & methods: DNA was isolated from 85 advanced cancer patients treated with 300 or 350 mg/m2 irinotecan and genotyped for haplotype-tag polymorphisms across TOP1, PARP1, TDP1 and XRCC1. Associations between genotypes and haplotypes and log(absolute neutrophil count nadirs) were assessed by linear regression. Results: No associations were observed. Conclusion: Our findings suggest that the genes we tested do not influence toxicity of irinotecan when adminstered at 300-350 mg/m2.

KW - Irinotecan

KW - PARP1

KW - Pharmacogenetics

KW - TDP1

KW - TOP1

KW - XRCC1

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Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan

Abstract

Keywords

ASJC Scopus subject areas

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