Title |
Genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer
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Published in |
Scientific Reports, January 2018
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DOI | 10.1038/s41598-018-19590-w |
Pubmed ID | |
Authors |
Bo Gao, Yi Lu, Annemieke J. M. Nieuweboer, Hongmei Xu, Jonathan Beesley, Ingrid Boere, Anne-Joy M. de Graan, Peter de Bruijn, Howard Gurney, Catherine J. Kennedy, Yoke-Eng Chiew, Sharon E. Johnatty, Philip Beale, Michelle Harrison, Craig Luccarini, Don Conroy, Ron H. J. Mathijssen, Paul R. Harnett, Rosemary L. Balleine, Georgia Chenevix-Trench, Stuart Macgregor, Anna de Fazio |
Abstract |
Identifying single nucleotide polymorphisms (SNPs) that influence chemotherapy disposition may help to personalize cancer treatment and limit toxicity. Genome-wide approaches are unbiased, compared with candidate gene studies, but usually require large cohorts. As most chemotherapy is given cyclically multiple blood sampling is required to adequately define drug disposition, limiting patient recruitment. We found that carboplatin and paclitaxel disposition are stable phenotypes in ovarian cancer patients and tested a genome-wide association study (GWAS) design to identify SNPs associated with chemotherapy disposition. We found highly significant SNPs in ABCC2, a known carboplatin transporter, associated with carboplatin clearance (asymptotic P = 5.2 × 106, empirical P = 1.4 × 10-5), indicating biological plausibility. We also identified novel SNPs associated with paclitaxel disposition, including rs17130142 with genome-wide significance (asymptotic P = 2.0 × 10-9, empirical P = 1.3 × 10-7). Although requiring further validation, our work demonstrated that GWAS of chemotherapeutic drug disposition can be effective, even in relatively small cohorts, and can be adopted in drug development and treatment programs. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Finland | 3 | 25% |
United States | 3 | 25% |
Australia | 1 | 8% |
China | 1 | 8% |
Unknown | 4 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 9 | 75% |
Scientists | 3 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 30 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 6 | 20% |
Student > Master | 6 | 20% |
Student > Bachelor | 4 | 13% |
Researcher | 3 | 10% |
Student > Postgraduate | 2 | 7% |
Other | 3 | 10% |
Unknown | 6 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 7 | 23% |
Medicine and Dentistry | 6 | 20% |
Agricultural and Biological Sciences | 3 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 7% |
Veterinary Science and Veterinary Medicine | 1 | 3% |
Other | 1 | 3% |
Unknown | 10 | 33% |