ABCB1 gene polymorphisms are associated with adverse reactions in fluoropyrimidine-treated colorectal cancer patients

作者：Gonzalez Haba Eva; Garcia Maria I; Cortejoso Lucia; Lopez Lillo Carolina; Burrueco Nelida; Garcia Alfonso Pilar; Alvarez Sonsoles; Jimenez Jose L; Martin Maria L; Munoz Fernandez Maria A; Sanjurjo Maria; Lopez Fernandez Luis A^*

来源：Pharmacogenomics, 2010, 11(12): 1715-1723.

DOI：10.2217/PGS.10.159

• 5-fluorouracil
• adverse reactions capecitabine
• ATP-binding cassette B1
• pharmacogenetics

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 ABM SNPs rs1128503 (C12361), rs2032592 (G2677T/A) and rs1045642 ((34351). 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.

• 出版日期2010-12