A genome-wide association study identifies four genetic markers for hematological toxicities in cancer patients receiving gemcitabine therapy

Kiyotani, Kazuma; Uno, Satoko; Mushiroda, Taisei; Takahashi, Atsushi; Kubo, Michiaki; Mitsuhata, Naoki; Ina, Shinomi; Kihara, Chikashi; Kimura, Yasutoshi; Yamaue, Hiroki; Hirata, Koichi; Nakamura, Yusuke; Zembutsu, Hitoshi

doi:10.1097/fpc.0b013e32834e9eba

Cited by 22 publications

(38 citation statements)

References 27 publications

(32 reference statements)

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“…36). As an expansion of this report, a large-scale pharmacogenomics study involving patients recruited from Biobank Japan who received therapy with various chemotherapeutic agents identified six suggestive loci (P < 1.0EÀ05), including rs9961113 between BDP1P and SALL3, rs2547917 in PDE4D, rs12900463 in ALPK3, rs9609078 in OSBP2, rs6863418 near to HMP19 and rs6037430 near to NRSN2, to be associated with gemcitabine-induced grade 3 or 4 leukopenia/neutropenia (37).…”

Section: Pancreatic Cancer (Gemcitabine)mentioning

confidence: 70%

Genome-Wide Association Study: A Useful Tool to Identify Common Genetic Variants Associated with Drug Toxicity and Efficacy in Cancer Pharmacogenomics

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Takahashi

Mushiroda

et al. 2014

Clinical Cancer Research

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In recent years, the utilization of genome-wide association study (GWAS) has proved to be a beneficial method to identify novel common genetic variations not only for disease susceptibility but also for drug efficacy and drug-induced toxicity, creating a field of pharmacogenomics studies. In addition, the findings from GWAS also generate new biologic hypotheses that could improve the understanding of pathophysiology for disease or the mechanism of drug-induced toxicity. This review highlights the implications of GWAS that have been published to date and discusses the successes as well as challenges of using GWAS in cancer pharmacogenomics. The aim of pharmacogenomics is to realize the vision of personalized medicine; it is hoped that through GWAS, novel common genetic variations could be identified to predict clinical outcome and/or toxicity in cancer therapies that subsequently could be implemented to improve the quality of lives of patients with cancer. Nevertheless, given the complexity of cancer therapies, underpowered studies, and large heterogeneity of study designs, collaborative efforts are needed to validate these findings and overcome the limitations of GWA studies before clinical implementation.

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Section: Pancreatic Cancer (Gemcitabine)mentioning

confidence: 70%

Genome-Wide Association Study: A Useful Tool to Identify Common Genetic Variants Associated with Drug Toxicity and Efficacy in Cancer Pharmacogenomics

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Takahashi

Mushiroda

et al. 2014

Clinical Cancer Research

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“…Estos estudios farmacogenéticos/farmacogenómicos están dirigidos a identificar variantes génicas o productos génicos que pueden modificar la magnitud del efecto farmacológico y los efectos secundarios e interacciones droga-droga 5,6,[17][18][19] .…”

Section: Variabilidad Farmacogenómica Y Medicina Personalizadaunclassified

Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica

et al. 2017

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Pharmacogenomics is an emergent field aimed at tailoring pharmacological therapy. Genetic polymorphisms can modify the expression and function of enzymes and proteins involved in drug metabolism, affecting absorption, distribution, biotransformation and excretion as well asU n hecho bien conocido es que los pacientes responden en forma diferente frente a la farmacoterapia y que ningún medicamento es 100% eficaz en todos los pacientes. Esta respuesta variable se debe, en gran medida, a factores genéticos, epigenéticos y ambientales, que afectan a las proteínas que metabolizan o transportan los fármacos, sus blancos terapéuticos (receptores) o ambos, influenciando tanto su eficacia como su seguridad, y en donde la contribución de cada factor varía en cada fármaco 1-4 . La Tabla 1 resume los factores que condicionan la variación interindividual en la respuesta a fármacos.Debido al desarrollo de técnicas no invasivas de ingeniería genética y biología molecular y a la necesidad de encontrar una explicación a las variaciones en la respuesta a la acción de fármacos es que actualmente la farmacogenómica ha adquirido gran relevancia en la investigación farmacológica. Es así como los resultados de los del Proyectos Genoma Humano 7 , Internacional HapMap 8 1.000 Genomas, el consorcio SNP 9 y los estudios GWAS (Genome-Wide Association Studies) 10 han aportado importantemente a nuestra comprensión de la variación genética humana 5,11,12 . Actualmente se sabe que existen 20.296 genes codificantes, 148.892.479 SNPs (polimorfismos de un solo nucleótido) y 4.363.564 variantes estructurales

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“…The paper from Kiyotani et al 1 provides novel markers of myelotoxicity of gemcitabine, an antimetabolite highly used in the treatment of pancreatic cancer patients, as well as in other diseases 2 . Myelotoxicity is the main side effect of gemcitabine and is clinically relevant, causing dose reductions and interruptions during the course of a patient therapy.…”

mentioning

confidence: 99%

“…The importance of the findings of Kiyotani et al 1 is to have mapped genomic regions associated with increased risk of neutropenia/leukopenia in Japanese patients treated with gemcitabine, moving away from the traditional, candidate gene pharmacogenetic studies and using a genome-wide approach. Leveraging the Japanese BioBank infrustructure of thousands of patients already interrogated for their genomic content, a case-control design (presence/absence of severe myelotoxicity) has identified four novel genomic regions.…”

mentioning

confidence: 99%

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Research Highlights: Highlights from the Latest Articles in Germline Genomics in Oncology

Innocenti¹

2012

Pharmacogenomics

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A genome-wide association study identifies four genetic markers for hematological toxicities in cancer patients receiving gemcitabine therapy

Abstract: We 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.

Cited by 22 publications

References 27 publications

Genome-Wide Association Study: A Useful Tool to Identify Common Genetic Variants Associated with Drug Toxicity and Efficacy in Cancer Pharmacogenomics

Genome-Wide Association Study: A Useful Tool to Identify Common Genetic Variants Associated with Drug Toxicity and Efficacy in Cancer Pharmacogenomics

Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica

Research Highlights: Highlights from the Latest Articles in Germline Genomics in Oncology

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