ArticlePharmacogenetics and genomics2012
A genome-wide association study identifies four genetic markers for hematological toxicities in cancer patients receiving gemcitabine therapy.
Article in Pharmacogenetics and genomics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 24 citations in OpenAlex.
- Persistent follicular cystitis following intravesical gemcitabine: a case series and literature review.BMC cancer · 2026Review
- The association of four genetic variants with myelosuppression in gemcitabine-treated Japanese is not evident in gemcitabine/carboplatin-treated Swedes.Basic & clinical pharmacology & toxicology · 2022Article
- Whole-genome sequencing and gene network modules predict gemcitabine/carboplatin-induced myelosuppression in non-small cell lung cancer patients.NPJ systems biology and applications · 2020Article
- Genes and variants in hematopoiesis-related pathways are associated with gemcitabine/carboplatin-induced thrombocytopenia.The pharmacogenomics journal · 2020Article
- Exploring predictive biomarkers from clinical genome-wide association studies via multidimensional hierarchical mixture models.European journal of human genetics : EJHG · 2019Article
- Review
- 'Toxgnostics': an unmet need in cancer medicine.Nature reviews. Cancer · 2014Review
- Implications of genome-wide association studies in cancer therapeutics.British journal of clinical pharmacology · 2013Review
- Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan.Cancer science · 2013Article
- Moving away from candidate genes: a 'genome-wise' discovery of gemcitabine myelotoxicity.Pharmacogenomics · 2012Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveGenetic factors are thought to be one of the causes of individual variability in the adverse reactions observed in cancer patients who received gemcitabine therapy. However, genetic factors determining the risk of adverse reactions of gemcitabine are not fully understood. PATIENTS AND
methodsTo identify a genetic factor(s) determining the risk of gemcitabine-induced leukopenia/neutropenia, we conducted a genome-wide association study, by genotyping over 610 000 single nucleotide polymorphisms (SNPs), and a replication study in a total of 174 patients, including 54 patients with at least grade 3 leukopenia/neutropenia and 120 patients without any toxicities.
resultsWe identified four loci possibly associated with gemcitabine-induced leukopenia/neutropenia [rs11141915 in DAPK1 on chromosome 9q21, combined P=1.27×10, odds ratio (OR)=4.10; rs1901440 on chromosome 2q12, combined P=3.11×10, OR=34.00; rs12046844 in PDE4B on chromosome 1p31, combined P=4.56×10, OR=4.13; rs11719165 on chromosome 3q29, combined P=5.98×10, OR=2.60]. When we examined the combined effects of these four SNPs, by classifying patients into four groups on the basis of the total number of risk genotypes of these four SNPs, significantly higher risks of gemcitabine-induced leukopenia/neutropenia were observed in the patients having two and three risk genotypes (P=6.25×10, OR=11.97 and P=4.13×10, OR=50.00, respectively) relative to patients with zero or one risk genotype.
conclusionWe identified four novel SNPs associated with gemcitabine-induced severe leukopenia/neutropenia. These SNPs might be applicable in predicting the risk of hematological toxicity in patients receiving gemcitabine therapy.
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