An association between RRM1 haplotype and gemcitabine-induced neutropenia in breast cancer patients

Young Rha Sun, Cheul Jeung Hei, Ho Choi Yeon, Ick Yang Woo, Ho Yoo Jin, Soo Kim Byung, Kyung Roh Jae, Cheol Chung Hyun

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Abstract

Purpose. We examined the pattern of single-nucleotide polymorphisms (SNPs) of gemcitabine metabolism-related and target genes in breast cancer patients and evaluated their association with drug response or toxicity. Patients and Methods. SNPs in deoxycytidine kinase (dCK), deoxycytidine monophosphate deaminase (DCTD), and ribonucleotide reductase M1 polypeptide (RRM1) were analyzed with genomic DNA of 10 breast cancer cell lines, 74 peripheral blood mononuclear cell (PBMC) samples from advanced breast cancer patients treated with gemcitabine, and 56 PBMC samples from healthy volunteers. Results. The incidences of SNPs of breast cancer patients were 1.4% in dCK (626 A>G), 10.8% in DCTD (315 T>C), 40.5% in the first RRM1 (1082 C>A), 44.6% in the second RRM1 (2455 A>G), 44.6% in the third RRM1 (2464 G>A), and 23% in two RRM1 sites (2455A>G and 2464G>A) that were similar to those of the normal control group. We found a double SNP of RRM1 (2455 A>G and 2464 G>A) to be the novel haplotype that was associated with a lower frequency of chemotherapy-induced toxicity, such as neutropenia (p < .01) and G-CSF requirement (p > .005). Conclusion. RRM1 haplotype showed an association with susceptibility to gemcitabine monotherapy in breast cancer patients.

Original languageEnglish
Pages (from-to)622-630
Number of pages9
JournalOncologist
Volume12
Issue number6
DOIs
Publication statusPublished - 2007 Jun 1

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gemcitabine
Ribonucleotide Reductases
Neutropenia
Haplotypes
Breast Neoplasms
Peptides
Single Nucleotide Polymorphism
DCMP Deaminase
Deoxycytidine Kinase
Blood Cells
Healthy Volunteers

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Sun, Young Rha ; Hei, Cheul Jeung ; Yeon, Ho Choi ; Woo, Ick Yang ; Jin, Ho Yoo ; Byung, Soo Kim ; Jae, Kyung Roh ; Hyun, Cheol Chung. / An association between RRM1 haplotype and gemcitabine-induced neutropenia in breast cancer patients. In: Oncologist. 2007 ; Vol. 12, No. 6. pp. 622-630.
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abstract = "Purpose. We examined the pattern of single-nucleotide polymorphisms (SNPs) of gemcitabine metabolism-related and target genes in breast cancer patients and evaluated their association with drug response or toxicity. Patients and Methods. SNPs in deoxycytidine kinase (dCK), deoxycytidine monophosphate deaminase (DCTD), and ribonucleotide reductase M1 polypeptide (RRM1) were analyzed with genomic DNA of 10 breast cancer cell lines, 74 peripheral blood mononuclear cell (PBMC) samples from advanced breast cancer patients treated with gemcitabine, and 56 PBMC samples from healthy volunteers. Results. The incidences of SNPs of breast cancer patients were 1.4{\%} in dCK (626 A>G), 10.8{\%} in DCTD (315 T>C), 40.5{\%} in the first RRM1 (1082 C>A), 44.6{\%} in the second RRM1 (2455 A>G), 44.6{\%} in the third RRM1 (2464 G>A), and 23{\%} in two RRM1 sites (2455A>G and 2464G>A) that were similar to those of the normal control group. We found a double SNP of RRM1 (2455 A>G and 2464 G>A) to be the novel haplotype that was associated with a lower frequency of chemotherapy-induced toxicity, such as neutropenia (p < .01) and G-CSF requirement (p > .005). Conclusion. RRM1 haplotype showed an association with susceptibility to gemcitabine monotherapy in breast cancer patients.",
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An association between RRM1 haplotype and gemcitabine-induced neutropenia in breast cancer patients. / Sun, Young Rha; Hei, Cheul Jeung; Yeon, Ho Choi; Woo, Ick Yang; Jin, Ho Yoo; Byung, Soo Kim; Jae, Kyung Roh; Hyun, Cheol Chung.

In: Oncologist, Vol. 12, No. 6, 01.06.2007, p. 622-630.

Research output: Contribution to journalArticle

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AU - Sun, Young Rha

AU - Hei, Cheul Jeung

AU - Yeon, Ho Choi

AU - Woo, Ick Yang

AU - Jin, Ho Yoo

AU - Byung, Soo Kim

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AU - Hyun, Cheol Chung

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N2 - Purpose. We examined the pattern of single-nucleotide polymorphisms (SNPs) of gemcitabine metabolism-related and target genes in breast cancer patients and evaluated their association with drug response or toxicity. Patients and Methods. SNPs in deoxycytidine kinase (dCK), deoxycytidine monophosphate deaminase (DCTD), and ribonucleotide reductase M1 polypeptide (RRM1) were analyzed with genomic DNA of 10 breast cancer cell lines, 74 peripheral blood mononuclear cell (PBMC) samples from advanced breast cancer patients treated with gemcitabine, and 56 PBMC samples from healthy volunteers. Results. The incidences of SNPs of breast cancer patients were 1.4% in dCK (626 A>G), 10.8% in DCTD (315 T>C), 40.5% in the first RRM1 (1082 C>A), 44.6% in the second RRM1 (2455 A>G), 44.6% in the third RRM1 (2464 G>A), and 23% in two RRM1 sites (2455A>G and 2464G>A) that were similar to those of the normal control group. We found a double SNP of RRM1 (2455 A>G and 2464 G>A) to be the novel haplotype that was associated with a lower frequency of chemotherapy-induced toxicity, such as neutropenia (p < .01) and G-CSF requirement (p > .005). Conclusion. RRM1 haplotype showed an association with susceptibility to gemcitabine monotherapy in breast cancer patients.

AB - Purpose. We examined the pattern of single-nucleotide polymorphisms (SNPs) of gemcitabine metabolism-related and target genes in breast cancer patients and evaluated their association with drug response or toxicity. Patients and Methods. SNPs in deoxycytidine kinase (dCK), deoxycytidine monophosphate deaminase (DCTD), and ribonucleotide reductase M1 polypeptide (RRM1) were analyzed with genomic DNA of 10 breast cancer cell lines, 74 peripheral blood mononuclear cell (PBMC) samples from advanced breast cancer patients treated with gemcitabine, and 56 PBMC samples from healthy volunteers. Results. The incidences of SNPs of breast cancer patients were 1.4% in dCK (626 A>G), 10.8% in DCTD (315 T>C), 40.5% in the first RRM1 (1082 C>A), 44.6% in the second RRM1 (2455 A>G), 44.6% in the third RRM1 (2464 G>A), and 23% in two RRM1 sites (2455A>G and 2464G>A) that were similar to those of the normal control group. We found a double SNP of RRM1 (2455 A>G and 2464 G>A) to be the novel haplotype that was associated with a lower frequency of chemotherapy-induced toxicity, such as neutropenia (p < .01) and G-CSF requirement (p > .005). Conclusion. RRM1 haplotype showed an association with susceptibility to gemcitabine monotherapy in breast cancer patients.

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