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Pharmacogenomics ; 11(12): 1715-23, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21142915

ABSTRACT

AIM: 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. MATERIALS & 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). CONCLUSION: 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.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Antimetabolites, Antineoplastic/adverse effects , Colorectal Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Polymorphism, Single Nucleotide , ATP Binding Cassette Transporter, Subfamily B , Aged , Antimetabolites, Antineoplastic/pharmacokinetics , Antimetabolites, Antineoplastic/therapeutic use , Capecitabine , Colorectal Neoplasms/genetics , DNA/blood , DNA/genetics , Deoxycytidine/adverse effects , Deoxycytidine/pharmacokinetics , Deoxycytidine/therapeutic use , Female , Fluorouracil/adverse effects , Fluorouracil/pharmacokinetics , Fluorouracil/therapeutic use , Genotype , Humans , Male , Middle Aged , Polymerase Chain Reaction , Retrospective Studies
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