title: An association between RRM1 haplotype and gemcitabine-induced neutropenia in breast cancer patients.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  RRM1 haplotype showed an association with susceptibility to gemcitabine monotherapy in breast cancer patients.
authors.affiliation: Cancer Metastasis Research Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gyu, Shinchon-dong 134, Seoul, Korea, 120-752.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Hei Cheul
authors.initials: HC
authors.lastname: Jeung
authors.forename: Yeon Ho
authors.initials: YH
authors.lastname: Choi
authors.forename: Woo Ick
authors.initials: WI
authors.lastname: Yang
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Yoo
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Roh
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003844:DCMP Deaminase / Q000235:genetics / Q000378:metabolism; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003842:Deoxycytidine Kinase / Q000235:genetics / Q000378:metabolism; D005260:Female; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012262:Ribonucleoside Diphosphate Reductase; D012264:Ribonucleotide Reductases / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D012264:Ribonucleotide Reductases; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D003842:Deoxycytidine Kinase; D003844:DCMP Deaminase; D000093542:Gemcitabine