ArticlePloS one2011
Genome-wide local ancestry approach identifies genes and variants associated with chemotherapeutic susceptibility in African Americans.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Pooled it
- Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- The long noncoding RNAThe Journal of biological chemistry · 2018Article
- Genome-Wide Association Studies of Chemotherapeutic Toxicities: Genomics of Inequality.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Review
- Article
- Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study.Environmental health perspectives · 2015Article
- Genome-wide association studies in Africans and African Americans: expanding the framework of the genomics of human traits and disease.Public health genomics · 2015Review
- Systems biology of cisplatin resistance: past, present and future.Cell death & disease · 2014Review
- Trans-population analysis of genetic mechanisms of ethnic disparities in neuroblastoma survival.Journal of the National Cancer Institute · 2013Article
- Integration of cell line and clinical trial genome-wide analyses supports a polygenic architecture of Paclitaxel-induced sensory peripheral neuropathy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Relating human genetic variation to variation in drug responses.Trends in genetics : TIG · 2012Review
- Whole-genome studies identify solute carrier transporters in cellular susceptibility to paclitaxel.Pharmacogenetics and genomics · 2012Article
- Using germline genomics to individualize pediatric cancer treatments.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Review
- Lymphoblastoid cell lines in pharmacogenomic discovery and clinical translation.Pharmacogenomics · 2012Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Chemotherapeutic agents are used in the treatment of many cancers, yet variable resistance and toxicities among individuals limit successful outcomes. Several studies have indicated outcome differences associated with ancestry among patients with various cancer types. Using both traditional SNP-based and newly developed gene-based genome-wide approaches, we investigated the genetics of chemotherapeutic susceptibility in lymphoblastoid cell lines derived from 83 African Americans, a population for which there is a disparity in the number of genome-wide studies performed. To account for population structure in this admixed population, we incorporated local ancestry information into our association model. We tested over 2 million SNPs and identified 325, 176, 240, and 190 SNPs that were suggestively associated with cytarabine-, 5'-deoxyfluorouridine (5'-DFUR)-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10(-4)). Importantly, some of these variants are found only in populations of African descent. We also show that cisplatin-susceptibility SNPs are enriched for carboplatin-susceptibility SNPs. Using a gene-based genome-wide association approach, we identified 26, 11, 20, and 41 suggestive candidate genes for association with cytarabine-, 5'-DFUR-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10(-3)). Fourteen of these genes showed evidence of association with their respective chemotherapeutic phenotypes in the Yoruba from Ibadan, Nigeria (p<0.05), including TP53I11, COPS5 and GAS8, which are known to be involved in tumorigenesis. Although our results require further study, we have identified variants and genes associated with chemotherapeutic susceptibility in African Americans by using an approach that incorporates local ancestry information.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.