ArticleCancer2018
Analyzing the clinical actionability of germline pharmacogenomic findings in oncology.
Article in Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Effects of polygenic risk score communication on short term health outcomes: systematic review and meta-analysis.BMJ medicine · 2026Article
- Modern developments in germline pharmacogenomics for oncology prescribing.CA: a cancer journal for clinicians · 2022Review
- Clinically actionable genotypes for anticancer prescribing among >1500 patients with pharmacogenomic testing.Cancer · 2022Article
- Pharmacogenetic Review: Germline Genetic Variants Possessing Increased Cancer Risk With Clinically Actionable Therapeutic Relationships.Frontiers in genetics · 2022Review
- Pharmacogenomics of breast cancer: highlighting CYP2D6 and tamoxifen.Journal of cancer research and clinical oncology · 2020Review
- The influence of ACYP2 polymorphisms on gastrointestinal cancer susceptibility in the Chinese Han population.Molecular genetics & genomic medicine · 2019Article
- Germline variants in cancer therapy.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Pharmacogenetics of asparaginase in acute lymphoblastic leukemia.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Impacts of Cytochrome P450 2D6 (CYP2D6) Genetic Polymorphism in Tamoxifen Therapy for Breast Cancer.Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia · 2018Review
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Authors and funding
8 authors.
Funding
Abstract
backgroundGermline and tumor pharmacogenomics impact drug responses, but germline markers less commonly guide oncology prescribing. The authors hypothesized that a critical number of clinically actionable germline pharmacogenomic associations exist, representing clinical implementation opportunities.
methodsIn total, 125 oncology drugs were analyzed for positive germline pharmacogenomic associations in journals with impact factors ≥5. Studies were assessed for design and genotyping quality, clinically relevant outcomes, statistical rigor, and evidence of drug-gene effects. Associations from studies of high methodologic quality were deemed potentially clinically actionable, and translational summaries were written as point-of-care clinical decision support (CDS) tools and formally evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.
resultsThe authors identified germline pharmacogenomic results for 56 of 125 oncology drugs (45%) across 173 publications. Actionable associations were detected for 12 drugs, including 6 that had germline pharmacogenomic information within US Food and Drug Administration labels or published guidelines (capecitabine/fluorouracil/dihydropyrimidine dehydrogenase [DPYD], irinotecan/uridine diphosphate glucuronosyltransferase family 1 member A1 [UGT1A1], mercaptopurine/thioguanine/thiopurine S-methyltransferase [TPMT], tamoxifen/cytochrome P450 [CYP] family 2 subfamily D member 6 [CYP2D6]), and 6 others were novel (asparaginase/nuclear factor of activated T-cells 2 [NFATC2]/human leukocyte antigen D-related β1 [HLA-DRB1], cisplatin/acylphosphatase 2 [ACYP2], doxorubicin/adenosine triphosphate-binding cassette subfamily C member 2/Rac family small guanosine triphosphatase 2/neutrophil cytosolic factor 4 [ABCC2/RAC2/NCF4], lapatinib/human leukocyte antigen DQ α1 [HLA-DQA1], sunitinib/cytochrome P450 family 3 subfamily A member 5 [CYP3A5], vincristine/centrosomal protein 72 [CEP72]). By using AGREE II, the developed CDS summaries had high mean ± standard deviation scores (maximum score, 100) for scope and purpose (92.7 ± 5.1) and rigour of development (87.6 ± 7.4) and moderate yet robust scores for clarity of presentation (58.6 ± 25.1) and applicability (55.9 ± 24.6). The overall mean guideline quality score was 5.2 ± 1.0 (maximum score, 7). Germline pharmacogenomic CDS summaries for these 12 drugs were recommended for implementation.
conclusionsSeveral oncology drugs have actionable germline pharmacogenomic information, justifying their delivery through institutional pharmacogenomic implementations to determine clinical utility. Cancer 2018;124:3052-65. © 2018 American Cancer Society.
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