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

被引:26
作者
Gonzalez-Haba, Eva [1 ]
Garcia, Maria I. [1 ]
Cortejoso, Lucia [1 ]
Lopez-Lillo, Carolina [1 ]
Burrueco, Nelida [1 ]
Garcia-Alfonso, Pilar
Alvarez, Sonsoles
Jimenez, Jose L.
Martin, Maria L. [1 ]
Munoz-Fernandez, Maria A.
Sanjurjo, Maria [1 ]
Lopez-Fernandez, Luis A. [1 ]
机构
[1] Hosp Gen Univ Gregorio Maranon, Lab Pharmacogenet & Pharmacogen, Serv Pharm, Madrid, Spain
关键词
5-fluorouracil; adverse reactions capecitabine; ATP-binding cassette B1; pharmacogenetics; PREDICTIVE BIOMARKERS; P-GLYCOPROTEIN; CHEMOTHERAPY; 5-FLUOROURACIL; IRINOTECAN; TOXICITY; TRIAL;
D O I
10.2217/PGS.10.159
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
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.
引用
收藏
页码:1715 / 1723
页数:9
相关论文
共 23 条
[1]
[Anonymous], COMMON TERMINOLOGY C
[2]
Role of Pharmacogenetics as Predictive Biomarkers of Response and/or Toxicity in the Treatment of Colorectal Cancer [J].
Bhushan, Shriya ;
McLeod, Howard ;
Walko, Christine M. .
CLINICAL COLORECTAL CANCER, 2009, 8 (01) :15-21
[3]
Predictive biomarkers of chemotherapy efficacy in colorectal cancer: Results from the UK MRC FOCUS trial [J].
Braun, Michael S. ;
Richman, Susan D. ;
Quirke, Philip ;
Daly, Catherine ;
Adlard, Julian W. ;
Elliott, Faye ;
Barrett, Jennifer H. ;
Selby, Peter ;
Meade, Angela M. ;
Stephens, Richard J. ;
Parmar, Mahesh K. B. ;
Seymour, Matthew T. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (16) :2690-2698
[4]
Association of Molecular Markers With Toxicity Outcomes in a Randomized Trial of Chemotherapy for Advanced Colorectal Cancer: The FOCUS Trial [J].
Braun, Michael S. ;
Richman, Susan D. ;
Thompson, Lindsay ;
Daly, Catherine L. ;
Meade, Angela M. ;
Adlard, Julian W. ;
Allan, James M. ;
Parmar, Mahesh K. B. ;
Quirke, Philip ;
Seymour, Matthew T. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (33) :5519-5528
[5]
Association of the ABCB1 3435C>T polymorphism and treatment outcomes in advanced gastric cancer patients treated with paclitaxel-based chemotherapy [J].
Chang, Hyun ;
Rha, Sun Young ;
Jeung, Hei-Cheul ;
Im, Chong Kun ;
Noh, Sung Hoon ;
Kim, Jin Ju ;
Chung, Hyun Cheol .
ONCOLOGY REPORTS, 2010, 23 (01) :271-278
[6]
De Iudicibus S, 2008, ANTICANCER RES, V28, P3921
[7]
GLIMELIUS B, 2010, PHARMACOGENOMICS J
[8]
ATP-Binding Cassette C Transporters in Human Pancreatic Carcinoma Cell Lines [J].
Hagmann, Wolfgang ;
Jesnowski, Ralf ;
Faissner, Ralf ;
Guo, Changqing ;
Lohr, J. Matthias .
PANCREATOLOGY, 2009, 9 (1-2) :136-144
[9]
Associations of ABCB1, ABCC2, and ABCG2 polymorphisms with irinotecan-pharmacokinetics and clinical outcome in patients with advanced non-small cell lung cancer [J].
Han, Ji-Youn ;
Lim, Hyeong-Seok ;
Yoo, Yeon-Kyeong ;
Shin, Eun Soon ;
Park, Yong Hoon ;
Lee, Sung Young ;
Lee, Jong-Eun ;
Lee, Dea Ho ;
Kim, Heung Tae ;
Lee, Jin Soo .
CANCER, 2007, 110 (01) :138-147
[10]
Hand-foot syndrome in patients treated with capecitabine-containing combination chemotherapy [J].
Heo, YS ;
Chang, HM ;
Kim, TW ;
Ryu, MH ;
Ahn, JH ;
Kim, SB ;
Lee, JS ;
Kim, WK ;
Cho, HK ;
Kang, YK .
JOURNAL OF CLINICAL PHARMACOLOGY, 2004, 44 (10) :1166-1172