title: Differential toxicity biomarkers for irinotecan- and oxaliplatin-containing chemotherapy in colorectal cancer.
abstract: OBJECTIVE
  Oxaliplatin or irinotecan is usually administered jointly with fluoropyrimidines in colorectal cancer patients treated with chemotherapy. Both drugs have different toxicity patterns. Biomarkers for predicting high-risk severe adverse reactions can help select the best treatment.
  
  
  METHODS
  A retrospective analysis of 106 colorectal cancer patients receiving an oxaliplatin-based treatment and 56 receiving an irinotecan-based treatment was performed. One copy number variant (GSTT1) and nine polymorphisms in irinotecan and oxaliplatin metabolism, transport or DNA repair genes (ABCB1, UGT1A1, XRCC1, ERCC1, ERCC2, GSTP1) were genotyped by SNaPshot, polymerase chain reactions' length fragments, or copy number assays.
  
  
  RESULTS
  In irinotecan-treated patients, T allele of ABCB1C1236T SNP was associated with a lower risk of asthenia(OR = 0.047; 95 % CI = 0.004–0.493; P = 0.011) and Tallele of ABCB1 C3435T SNP was associated with a lower risk of diarrhea (OR = 0.177; 95 % CI = 0.034–0.919;P = 0.039), and individuals with two copies of GSTT1 gene had a lower risk for asthenia (OR = 0.093; 95 %CI = 0.011–0.794; P = 0.030). In oxaliplatin-treated patients, carriers of one or two T variants of Asn118Asn ERCC1 SNP had a lower risk for neutropenia(OR = 0.205; 95 % CI = 0.061–0.690; P = 0.01) [corrected].
  
  
  CONCLUSIONS
  These biomarkers could help oncologists select the best treatment by reducing toxicity associated with irinotecan or oxaliplatin in colorectal cancer patients, thus increasing their quality of life.
authors.affiliation: Servicio de Farmacia, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Doctor Esquerdo 46, 28007 Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Cortejoso
authors.forename: María I
authors.initials: MI
authors.lastname: García
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Alfonso
authors.forename: Eva
authors.initials: E
authors.lastname: González-Haba
authors.forename: Fernando
authors.initials: F
authors.lastname: Escolar
authors.forename: María
authors.initials: M
authors.lastname: Sanjurjo
authors.forename: Luis A
authors.initials: LA
authors.lastname: López-Fernández
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000077150:Oxaliplatin; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D004247:DNA; D002166:Camptothecin