John Jack1,2, Tammy M Havener3, Howard L McLeod4,5, Alison A Motsinger-Reif1,2, Matthew Foster6. 1. Department of Statistics, North Carolina State University, 2601 Stinson Drive, Raleigh, NC 27695, USA. 2. Bioinformatics Research Center, North Carolina State University, 2601 Stinson Drive, Raleigh, NC 27695, USA. 3. Center for Pharmacogenomics & Individualized Therapy, University of North Carolina, 120 Mason Farm Road, Chapel Hill, NC 27514, USA. 4. DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA. 5. Pharmacogenetics for Every Nation Initiative, 1119 Oxbridge Drive, Tampa, FL 33549, USA. 6. Lineberger Comprehensive Cancer Center, University of North Carolina, 101 Manning Drive, Chapel Hill, NC 27514, USA.
Abstract
AIM: We investigate the role of ethnicity and admixture in drug response across a broad group of chemotherapeutic drugs. Also, we generate hypotheses on the genetic variants driving differential drug response through multivariate genome-wide association studies. METHODS: Immortalized lymphoblastoid cell lines from 589 individuals (Hispanic or non-Hispanic/Caucasian) were used to investigate dose-response for 28 chemotherapeutic compounds. Univariate and multivariate statistical models were used to elucidate associations between genetic variants and differential drug response as well as the role of ethnicity in drug potency and efficacy. RESULTS & CONCLUSION: For many drugs, the variability in drug response appears to correlate with self-reported race and estimates of genetic ancestry. Additionally, multivariate genome-wide association analyses offered interesting hypotheses governing these differential responses.
AIM: We investigate the role of ethnicity and admixture in drug response across a broad group of chemotherapeutic drugs. Also, we generate hypotheses on the genetic variants driving differential drug response through multivariate genome-wide association studies. METHODS: Immortalized lymphoblastoid cell lines from 589 individuals (Hispanic or non-Hispanic/Caucasian) were used to investigate dose-response for 28 chemotherapeutic compounds. Univariate and multivariate statistical models were used to elucidate associations between genetic variants and differential drug response as well as the role of ethnicity in drug potency and efficacy. RESULTS & CONCLUSION: For many drugs, the variability in drug response appears to correlate with self-reported race and estimates of genetic ancestry. Additionally, multivariate genome-wide association analyses offered interesting hypotheses governing these differential responses.
Entities:
Keywords:
Caucasian; GWAS; admixture; cancer; cytotoxicity; drug; genome-wide association study; hispanic; in vitro; lymphoblastoid cell lines
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