Fax: (713) 834-6153
Gemcitabine metabolic and transporter gene polymorphisms are associated with drug toxicity and efficacy in patients with locally advanced pancreatic cancer
Article first published online: 3 NOV 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 22, pages 5325–5335, 15 November 2010
How to Cite
Tanaka, M., Javle, M., Dong, X., Eng, C., Abbruzzese, J. L. and Li, D. (2010), Gemcitabine metabolic and transporter gene polymorphisms are associated with drug toxicity and efficacy in patients with locally advanced pancreatic cancer. Cancer, 116: 5325–5335. doi: 10.1002/cncr.25282
- Issue published online: 3 NOV 2010
- Article first published online: 3 NOV 2010
- Manuscript Accepted: 12 JAN 2010
- Manuscript Revised: 30 DEC 2009
- Manuscript Received: 15 OCT 2009
- gemcitabine metabolism;
- nucleoside transporter;
- single nucleotide polymorphism;
- locally advanced pancreatic cancer
It has not been well established whether genetic variations can be biomarkers for clinical outcome of gemcitabine therapy. The purpose of this study was to identify single nucleotide polymorphisms (SNPs) of gemcitabine metabolic and transporter genes that are associated with toxicity and efficacy of gemcitabine-based therapy in patients with locally advanced pancreatic cancer.
The authors evaluated 17 SNPs of the CDA,dCK, DCTD, RRM1, hCNT1-3, and hENT1 genes in 149 patients with locally advanced pancreatic cancer who underwent gemcitabine-based chemoradiotherapy. The association of genotypes with neutropenia, tumor response to therapy, overall survival, and progression-free survival (PFS) was analyzed by logistic regression, log-rank test, Kaplan-Meier plot, and Cox proportional hazards regression.
The CDA A-76C, dCK C-1205T, RRM1 A33G, and hENT1 C913T genotypes were significantly associated with grade 3 to 4 neutropenia (P = .020, .015, .003, and .017, respectively).The CDA A-76C and hENT1 A-201G genotypes were significantly associated with tumor response to therapy (P = .017 and P = .019). A combined genotype effect of CDA A-76C, RRM1 A33G, RRM1 C-27A, and hENT1 A-201G on PFS was observed. Patients carrying 0 to 1 (n = 64), 2 (n = 50), or 3 to 4 (n = 17) at-risk genotypes had median PFS times of 8.3, 6.0, and 4.2 months, respectively (P = .002).
The results indicated that some polymorphic variations of drug metabolic and transporter genes may be potential biomarkers for clinical outcome of gemcitabine-based therapy in patients with locally advanced pancreatic cancer. Cancer 2010. © 2010 American Cancer Society.