ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Platinum sensitivity-related germline polymorphism discovered via a cell-based approach and analysis of its association with outcome in ovarian cancer patients.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Pooled it
- Prognostically relevant gene signatures of high-grade serous ovarian carcinoma.The Journal of clinical investigation · 2013Trial
- The Molecular Landscape Influencing Prognoses of Epithelial Ovarian Cancer.Biomolecules · 2021Review
- Extending the lymphoblastoid cell line model for drug combination pharmacogenomics.Pharmacogenomics · 2021Review
- Genomic Variants of Cytarabine Sensitivity Associated with Treatment-Related Mortality in Pediatric AML: A Report from the Children's Oncology Group.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Pharmacogenomics in epithelial ovarian cancer first-line treatment outcome: validation of GWAS-associated NRG3 rs1649942 and BRE rs7572644 variants in an independent cohort.The pharmacogenomics journal · 2019Article
- Exceptional durable response to everolimus in a patient with biphenotypic breast cancer harboring anCold Spring Harbor molecular case studies · 2017Article
- Clinical Evaluation of Cisplatin Sensitivity of Germline Polymorphisms in Neoadjuvant Chemotherapy for Urothelial Cancer.Clinical genitourinary cancer · 2016Article
- Utility of patient-derived lymphoblastoid cell lines as an ex vivo capecitabine sensitivity prediction model for breast cancer patients.Oncotarget · 2016Article
- Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer.Oncotarget · 2016Article
- Genomic/Epigenomic Alterations in Ovarian Carcinoma: Translational Insight into Clinical Practice.Journal of Cancer · 2016Review
- Genome-Wide Study of Response to Platinum, Taxane, and Combination Therapy in Ovarian Cancer: In vitro Phenotypes, Inherited Variation, and Disease Recurrence.Frontiers in genetics · 2016Article
- Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- In vitro human cell line models to predict clinical response to anticancer drugs.Pharmacogenomics · 2015Review
- Integrating cell-based and clinical genome-wide studies to identify genetic variants contributing to treatment failure in neuroblastoma patients.Clinical pharmacology and therapeutics · 2014Article
- The impact of functional LIG4 polymorphism on platinum-based chemotherapy response and survival in non-small cell lung cancer.Medical oncology (Northwood, London, England) · 2014Article
- The impact of smoking on pathologic response to neoadjuvant cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer.World journal of urology · 2014Article
- Protein quantitative trait loci identify novel candidates modulating cellular response to chemotherapy.PLoS genetics · 2014Article
- STAT3 Single Nucleotide Polymorphism rs4796793 SNP Does Not Correlate with Response to Adjuvant IFNα Therapy in Stage III Melanoma Patients.Frontiers in medicine · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors at 6 institutions in 3 countries.
Funding
Abstract
purposeCell-based approaches were used to identify genetic markers predictive of patients' risk for poor response prior to chemotherapy. EXPERIMENTAL
designWe conducted genome-wide association studies (GWAS) to identify single-nucleotide polymorphisms (SNP) associated with cellular sensitivity to carboplatin through their effects on mRNA expression using International HapMap lymphoblastoid cell lines (LCL) and replicated them in additional LCLs. SNPs passing both stages of the cell-based study were tested for association with progression-free survival (PFS) in patients. Phase 1 validation was based on 377 ovarian cancer patients receiving at least four cycles of carboplatin and paclitaxel from the Australian Ovarian Cancer Study (AOCS). Positive associations were then assessed in phase 2 validation analysis of 1,326 patients from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas.
resultsIn the initial GWAS, 342 SNPs were associated with carboplatin-induced cytotoxicity, of which 18 unique SNPs were retained after assessing their association with gene expression. One SNP (rs1649942) was replicated in an independent LCL set (Bonferroni adjusted P < 0.05). It was found to be significantly associated with decreased PFS in phase 1 AOCS patients (P(per-allele) = 2 × 10(-2)), with a stronger effect in the subset of women with optimally debulked tumors (P(per-allele) = 4 × 10(-3)). rs1649942 was also associated with poorer overall survival in women with optimally debulked tumors (P(per-allele) = 9 × 10(-3)). However, this SNP was not significant in phase 2 validation analysis with patients from numerous cohorts.
conclusionThis study shows the potential of cell-based, genome-wide approaches to identify germline predictors of treatment outcome and highlights the need for extensive validation in patients to assess their clinical effect.
Indexed as
Identifiers
What OpenQuestion holds
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.