SynthesisCancer2012
Identification of novel germline polymorphisms governing capecitabine sensitivity.
Synthesis in Cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03127111 (The Identification, Validation and Implementation of Molecular Markers to Predict Response to Fluorouracil-based Adjuvant Chemotherapy in Stage III Colorectal Cancer Patients - Prospective Clinical Observational Study), which is not on this map. Cited by 20 papers.
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.
The Identification, Validation and Implementation of Molecular Markers to Predict Response to Fluorouracil-based Adjuvant Chemotherapy in Stage III Colorectal Cancer Patients - Prospective Clinical Observational Study
Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Discovering novel germline genetic variants linked to severe fluoropyrimidine-related toxicity in- and outside DPYD.Genome medicine · 2024Article
- Integrated bioinformatics investigation of adenylyl cyclase family co-expression network in bladder cancer followed by preliminary validation of member 2 (Translational cancer research · 2024Article
- Loss of smarcad1a accelerates tumorigenesis of malignant peripheral nerve sheath tumors in zebrafish.Genes, chromosomes & cancer · 2021Article
- Genetically regulated expression underlies cellular sensitivity to chemotherapy in diverse populations.Human molecular genetics · 2021Article
- Genetic Variations of Ultraconserved Elements in the Human Genome.Omics : a journal of integrative biology · 2019Article
- Review
- Integration of genetic and functional genomics data to uncover chemotherapeutic induced cytotoxicity.The pharmacogenomics journal · 2019Article
- SMARCAD1 Promotes Pancreatic Cancer Cell Growth and Metastasis through Wnt/β-catenin-Mediated EMT.International journal of biological sciences · 2019Article
- Genome-wide association study evaluating single-nucleotide polymorphisms and outcomes in patients with advanced stage serous ovarian or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study.Gynecologic oncology · 2017Article
- Exceptional durable response to everolimus in a patient with biphenotypic breast cancer harboring anCold Spring Harbor molecular case studies · 2017Article
- New frontiers in the treatment of colorectal cancer: Autophagy and the unfolded protein response as promising targets.Autophagy · 2017Review
- Utility of patient-derived lymphoblastoid cell lines as an ex vivo capecitabine sensitivity prediction model for breast cancer patients.Oncotarget · 2016Article
- Predicting the Survival Time for Bladder Cancer Using an Additive Hazards Model in Microarray Data.Iranian journal of public health · 2016Article
- Open pipelines for integrated tumor genome profiles reveal differences between pancreatic cancer tumors and cell lines.Cancer medicine · 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
- Identification of genetic variants associated with capecitabine-induced hand-foot syndrome through integration of patient and cell line genomic analyses.Pharmacogenetics and genomics · 2014Article
- Protein quantitative trait loci identify novel candidates modulating cellular response to chemotherapy.PLoS genetics · 2014Article
- 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
- Clinical management of localized colon cancer with capecitabine.Clinical Medicine Insights. Oncology · 2012Article
- Pharmacogenomics of chemotherapeutic susceptibility and toxicity.Genome medicine · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCapecitabine, an oral 5-fluorouracil (5-FU) prodrug, is widely used in the treatment of breast, colorectal, and gastric cancers. To guide the selection of patients with potentially the greatest benefit of experiencing antitumor efficacy, or, alternatively, of developing toxicities, identifying genomic predictors of capecitabine sensitivity could permit its more informed use.
methodsThe objective of this study was to perform capecitabine sensitivity genome-wide association studies (GWAS) using 503 well genotyped human cell lines from individuals representing multiple different world populations. A meta-analysis that included all ethnic populations then enabled the identification of novel germline determinants (single nucleotide polymorphisms [SNPs]) of capecitabine susceptibility.
resultsFirst, an intrapopulation GWAS of Caucasian individuals identified reference SNP 4702484 (rs4702484) (within adenylate cyclase 2 [ADCY2]) at a level reaching genome-wide significance (P = 5.2 × 10(-8) ). This SNP is located upstream of the 5 methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene, and it is known that the enzyme for MTRR is involved in the methionine-folate biosynthesis and metabolism pathway, which is the primary target of 5-FU-related compounds, although the authors were unable to identify a direct relation between rs4702484 and MTRR expression in a tested subset of cells. In the meta-analysis, 4 SNPs comprised the top hits, which, again, included rs4702484 and 3 additional SNPs (rs8101143, rs576523, and rs361433) that approached genome-wide significance (P values from 1.9 × 10(-7) to 8.8 × 10(-7) ). The meta-analysis also identified 1 missense variant (rs11722476; serine to asparagine) within switch/sucrose nonfermentable-related, matrix-associated, actin-dependent regulator of chromatin (SMARCAD1), a novel gene for association with capecitabine/5-FU susceptibility.
conclusionsToward the goal of individualizing cancer chemotherapy, the current study identified novel SNPs and genes associated with capecitabine sensitivity that are potentially informative and testable in any patient regardless of ethnicity.
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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.