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The Oncologist, Vol. 12, No. 6, 622-630, June 2007; doi:10.1634/theoncologist.12-6-622
© 2007 AlphaMed Press

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Breast Cancer

An Association Between RRM1 Haplotype and Gemcitabine-Induced Neutropenia in Breast Cancer Patients

Sun Young Rhaa,c, Hei Cheul Jeunga,b, Yeon Ho Choia,c, Woo Ick Yangc,e, Jin Ho Yooa,c, Byung Soo Kima,b, Jae Kyung Roha,d, Hyun Cheol Chunga,d

aCancer Metastasis Research Center, bYonsei Cancer Center, cBrain Korea 21 Project for Medical Sciences, dDepartment of Internal Medicine, eDepartment of Pathology, Yonsei University College of Medicine, Seoul, Korea

Correspondence: Hyun Cheol Chung, M.D., Ph.D., Cancer Metastasis Research Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gyu, Shinchon-dong 134, Seoul, Korea, 120-752. Telephone: 82-2-2228-8132; Fax: 82-2-393-3652; e-mail: unchung8{at}yumc.yonsei.ac.kr

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 (2455 A>G and 2464 G>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.

Disclosure of potential conflicts of interest is found at the end of this article.




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[Abstract] [Full Text] [PDF]


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