Genetic Variations of Drug Transporters Can Influence on Drug Response in Patients Treated with Docetaxel Chemotherapy
- Authors
- Choi, Jung Ran; Kim, Jeong-Oh; Kang, Dae Ryong; Shin, Jung-Young; Zhang, Xiang Hua; Oh, Ji Eun; Park, Ji-Young; Kim, Kyoung-Ah; Kang, Jin-Hyoung
- Issue Date
- 7월-2015
- Publisher
- KOREAN CANCER ASSOCIATION
- Keywords
- Docetaxel; Genetic predictor; Single nucleotide polymorphism; Tumor response
- Citation
- CANCER RESEARCH AND TREATMENT, v.47, no.3, pp.509 - 517
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- CANCER RESEARCH AND TREATMENT
- Volume
- 47
- Number
- 3
- Start Page
- 509
- End Page
- 517
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/93079
- DOI
- 10.4143/crt.2014.012
- ISSN
- 1598-2998
- Abstract
- Purpose Dose-limiting toxicities of docetaxel are widely considered to be neutropenia, anemia, skin toxicity, and nausea. One of the factors that limit the use of docetaxel is its unpredictability of inter-individual variation in toxicity. Materials and Methods In order to identify the genetic factors that affect the risk of docetaxel-induced toxicities, we recruited patients who received docetaxel chemotherapy. We genotyped 92 patients with single-nucleotide polymorphisms (SNPs) in 5 genes: CYP3A4 (CYP3A4*1B, CYP3A4*18, and CYP3A4*3), CYP3A5 (CYP3A5*2 and CYP3A5*3), ABCB1 (C1236T, G2677G/T, and C3435T), SLCO1B3 (rs11045585), and ABCC2 (rs12762549). Results Out of 92 patients, 70 had grade 3 or 4 neutropenia; 4 had grade 1 or 2; and 18 had no toxicity (76.1%, 4.3%, and 19.6%, respectively). The findings of the SNP analysis showed that patients with TT genotype of ABCB1 3435C>T polymorphism showed significantly higher risk of neutropenia and anemia (p=0.029 and p=0.044, respectively). There were significant associations between docetaxel-induced leucopenia and 2677G/T of ABCB1 and rs12762549 of ABCC2 (p=0.025 and p=0.028, respectively). In a multivariate analysis, we observed that patients carrying 2677G>T in ABCB1 might be associated with higher risk of chemo-resistance when treated with docetaxel (odds ratio [OR], 6.48; confidence interval, 1.92 to 21.94; p=0.003). In a subgroup analysis of non-small cell lung cancer patients, a significant association of tumor response with G2677T/A (OR, 4.54) in ABCB1 and SLCO1B3 (OR, 9.44) was observed. Conclusion Our data suggest that ABCB1 (2677G/T) and SLCO1B3 (rs11055585) might be major genetic predictors of docetaxel-related toxicities in patients receiving docetaxel chemotherapy.
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