ArticlePharmacogenetics and genomics2008
Susceptibility loci involved in cisplatin-induced cytotoxicity and apoptosis.
Article in Pharmacogenetics and genomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Meta-analysis on pharmacogenetics of platinum-based chemotherapy in non small cell lung cancer (NSCLC) patients.PloS one · 2012Pooled it
- Promoter region variation in NFE2L2 influences susceptibility to ototoxicity in patients exposed to high cumulative doses of cisplatin.The pharmacogenomics journal · 2017Article
- Chemotherapy-induced peripheral neurotoxicity and ototoxicity: new paradigms for translational genomics.Journal of the National Cancer Institute · 2014Review
- Article
- Functional consequences of PRPF39 on distant genes and cisplatin sensitivity.Human molecular genetics · 2012Article
- Relating human genetic variation to variation in drug responses.Trends in genetics : TIG · 2012Review
- Lymphoblastoid cell lines in pharmacogenomic discovery and clinical translation.Pharmacogenomics · 2012Review
- Genetic variation predicting cisplatin cytotoxicity associated with overall survival in lung cancer patients receiving platinum-based chemotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011Article
- Chemotherapeutic-induced apoptosis: a phenotype for pharmacogenomics studies.Pharmacogenetics and genomics · 2011Article
- Pharmacogenomics of cisplatin-induced ototoxicity.Pharmacogenomics · 2011Review
- Genome-wide association study of survival in non-small cell lung cancer patients receiving platinum-based chemotherapy.Journal of the National Cancer Institute · 2011Article
- The use of genomic information to optimize cancer chemotherapy.Seminars in oncology · 2011Review
- Heritable and non-genetic factors as variables of pharmacologic phenotypes in lymphoblastoid cell lines.The pharmacogenomics journal · 2010Article
- Testicular cancer survivorship: research strategies and recommendations.Journal of the National Cancer Institute · 2010Review
- Identification of quantitative trait loci underlying proteome variation in human lymphoblastoid cells.Molecular & cellular proteomics : MCP · 2010Article
- Population differences in platinum toxicity as a means to identify novel genetic susceptibility variants.Pharmacogenetics and genomics · 2010Article
- Pharmacogenomic discovery using cell-based models.Pharmacological reviews · 2009Review
- Gemcitabine and arabinosylcytosin pharmacogenomics: genome-wide association and drug response biomarkers.PloS one · 2009Article
- A Bayesian hierarchical nonlinear model for assessing the association between genetic variation and drug cytotoxicity.Statistics in medicine · 2009Article
- Pharmacogenomics of platinum-based chemotherapy in NSCLC.Expert opinion on drug metabolism & toxicology · 2009Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
objectivesCisplatin is a widely used chemotherapeutic agent; however, nephrotoxicity and neuropathy are obstacles for drug efficacy. Little is known about the genes or genetic variants contributing to the risk of developing these toxicities or chemotherapeutic response. Thus, we have applied a cell-based model to identify and characterize previously unknown genes that may be involved in cellular susceptibility to cisplatin.
methodsLymphoblastoid cell lines from 27 large Centre d'Etude du Polymorphisme Humain pedigrees were used to elucidate the genetic contribution to cisplatin-induced cytotoxicity. Phenotype was defined as cell growth inhibition following exposure of cell lines to increasing concentrations of cisplatin for 48 h.
resultsSignificant heritability, ranging from 0.32 to 0.43 (P<10), was found for the cytotoxic effects of each concentration (1, 2.5, 5, 10, and 20 micromol/l) and IC50, the concentration required for 50% cell growth inhibition. Linkage analysis revealed 11 genomic regions on six chromosomes with logarithm of odds (LOD) scores above 1.5 for cytotoxic phenotypes. The highest LOD score was found on chromosome 4q21.3-q35.2 (LOD=2.65, P=2.4x10(-4)) for 5 micromol/l cisplatin. Quantitative transmission disequilibrium tests were performed using 191973 nonredundant single nucleotide polymorphisms (SNPs) located in the 1 LOD confidence interval of these 11 regions. Twenty SNPs, with 10 SNPs located in five genes, were significantly associated with cisplatin-induced cytotoxicity (P<or=1x10(-4)). Four of these 20 SNPs were found to explain over 10% of the variation in cisplatin-induced apoptosis.
conclusionsOur results suggest that genetic factors involved in cytotoxicity also contribute to cisplatin-induced apoptosis. These cell lines provide a paradigm to identify previously unknown pharmacogenetic variants associated with drug cytotoxicity.
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