ArticlePharmacogenetics and genomics2012
Gemcitabine metabolic pathway genetic polymorphisms and response in patients with non-small cell lung cancer.
Article in Pharmacogenetics and genomics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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15 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
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- The Impact of the Rs1044457 Polymorphism in the CMPK1 Gene on the Response Rate to Gemcitabine-Based Chemotherapy in Metastatic NSCLC Patients.Advanced genetics (Hoboken, N.J.) · 2025Article
- 5'-nucleotidase cN-II emerges as a new predictive biomarker of response to gemcitabine/platinum combination chemotherapy in non-small cell lung cancer.Oncotarget · 2018Article
- Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer.BMC genomics · 2016Article
- Knockdown of POLA2 increases gemcitabine resistance in lung cancer cells.BMC genomics · 2016Article
- Impact of Polymorphic Variations of Gemcitabine Metabolism, DNA Damage Repair, and Drug-Resistance Genes on the Effect of High-Dose Chemotherapy for Relapsed or Refractory Lymphoid Malignancies.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2016Article
- [NT5C2 expression in children with acute leukemia and its clinical significance].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2015Article
- RNA expression of genes involved in cytarabine metabolism and transport predicts cytarabine response in acute myeloid leukemia.Pharmacogenomics · 2015Article
- In vitro human cell line models to predict clinical response to anticancer drugs.Pharmacogenomics · 2015Review
- Prognostic significance of BRCA1, ERCC1, RRM1, and RRM2 in patients with advanced non-small cell lung cancer receiving chemotherapy.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Article
- Expression of RRM1 and RRM2 as a novel prognostic marker in advanced non-small cell lung cancer receiving chemotherapy.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Impact of polymorphisms in drug pathway genes on disease-free survival in adults with acute myeloid leukemia.Journal of human genetics · 2013Article
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14 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
objectiveGemcitabine is widely used to treat non-small cell lung cancer (NSCLC). The aim of this study was to assess the pharmacogenomic effects of the entire gemcitabine metabolic pathway, we genotyped single nucleotide polymorphisms (SNPs) within the 17 pathway genes using DNA samples from patients with NSCLC treated with gemcitabine to determine the effect of genetic variants within gemcitabine pathway genes on overall survival (OS) of patients with NSCLC after treatment of gemcitabine.
methodsEight of the 17 pathway genes were resequenced with DNA samples from Coriell lymphoblastoid cell lines (LCLs) using Sanger sequencing for all exons, exon-intron junctions, and 5'-, 3'-UTRs. A total of 107 tagging SNPs were selected on the basis of the resequencing data for the eight genes and on HapMap data for the remaining nine genes, followed by successful genotyping of 394 NSCLC patient DNA samples. Association of SNPs/haplotypes with OS was performed using the Cox regression model, followed by functional studies performed with LCLs and NSCLC cell lines.
resultsFive SNPs in four genes (CDA, NT5C2, RRM1, and SLC29A1) showed associations with OS of those patients with NSCLC, as well as nine haplotypes in four genes (RRM1, RRM2, SLC28A3, and SLC29A1) with a P value of less than 0.05. Genotype imputation using the LCLs was performed for a region of 200 kb surrounding those SNPs, followed by association studies with gemcitabine cytotoxicity. Functional studies demonstrated that downregulation of SLC29A1, NT5C2, and RRM1 in NSCLC cell lines altered cell susceptibility to gemcitabine.
conclusionThese studies help in identifying biomarkers to predict gemcitabine response in NSCLC, a step toward the individualized chemotherapy of lung cancer.
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