title: ABCB1 gene polymorphisms are associated with adverse reactions in fluoropyrimidine-treated colorectal cancer patients.
abstract: OBJECTIVE
  To find out whether SNPs in the transporter gene ATP-binding casette B1 (ABCB1) were related to adverse effects in colorectal cancer patients treated with 5-fluorouracil (5-FU) or capecitabine.
  
  
  METHODS
  Patients treated with a 5-FU-based therapy (n = 67) or a capecitabine-based therapy (n = 74) were recruited and genotyped for the ABCB1 SNPs rs1128503 (C1236T), rs2032592 (G2677T/A) and rs1045642 (C3435T). Clinical data and adverse reactions were recorded. ABCB1 genotypes of patients were statistically analyzed for association with the most frequent adverse reactions.
  
  
  RESULTS
  Statistical associations were observed, suggesting a lower risk of neutropenia (p = 0.013) and hand-foot syndrome (HFS; p = 0.027) for the carriers of T variation for rs1128503 in capecitabine-treated patients, carriers of T variation for rs1045642 treated with capecitabine had a lower risk of HFS (p = 0.033), while those treated with 5-FU had a higher risk of diarrhea (p = 0.035), and carriers of T variation for rs2032592 treated with capecitabine were at less risk of developing HFS (p = 0.033).
  
  
  CONCLUSIONS
  This is the first time evidence has been found of differing pharmacogenetic markers for capecitabine and 5-FU treatments. Genotyping of SNPs in the ABCB1 gene prior to chemotherapy administration could help reduce adverse reactions in colorectal cancer patients.
authors.affiliation: Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Gonzalez-Haba
authors.forename: Maria I
authors.initials: MI
authors.lastname: García
authors.forename: Lucia
authors.initials: L
authors.lastname: Cortejoso
authors.forename: Carolina
authors.initials: C
authors.lastname: López-Lillo
authors.forename: Nélida
authors.initials: N
authors.lastname: Barrueco
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Alfonso
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Alvarez
authors.forename: Jose L
authors.initials: JL
authors.lastname: Jiménez
authors.forename: María L
authors.initials: ML
authors.lastname: Martín
authors.forename: Maria A
authors.initials: MA
authors.lastname: Muñóz-Fernández
authors.forename: María
authors.initials: M
authors.lastname: Sanjurjo
authors.forename: Luis A
authors.initials: LA
authors.lastname: López-Fernández
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D004247:DNA; D005472:Fluorouracil