ArticleJournal of cancer research and clinical oncology2012
Roles of genetic variants in the PI3K and RAS/RAF pathways in susceptibility to endometrial cancer and clinical outcomes.
Article in Journal of cancer research and clinical oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 4 of them syntheses that pooled it.
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30 citing papers in PubMed, 4 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- Biomolecular and Genetic Prognostic Factors That Can Facilitate Fertility-Sparing Treatment (FST) Decision Making in Early Stage Endometrial Cancer (ES-EC): A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Genetic polymorphisms of mTOR and cancer risk: a systematic review and updated meta-analysis.Oncotarget · 2016Pooled it
- Associations of PI3KR1 and mTOR polymorphisms with esophageal squamous cell carcinoma risk and gene-environment interactions in Eastern Chinese populations.Scientific reports · 2015Pooled it
- Association of mTOR polymorphisms with cancer risk and clinical outcomes: a meta-analysis.PloS one · 2014Pooled it
- Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.Nature genetics · 2024Article
- mTOR pathway candidate genes and obesity interaction on breast cancer risk in black women from the Women's Circle of Health Study.Cancer causes & control : CCC · 2023Article
- Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant.NPJ breast cancer · 2022Article
- Polymorphisms in the mTOR-PI3K-Akt pathway, energy balance-related exposures and colorectal cancer risk in the Netherlands Cohort Study.BioData mining · 2022Article
- Clinical Development of AKT Inhibitors and Associated Predictive Biomarkers to Guide Patient Treatment in Cancer Medicine.Pharmacogenomics and personalized medicine · 2021Review
- MassArray analysis of genomic susceptibility variants in ovarian cancer.Scientific reports · 2020Article
- Comprehensive analysis of the effect of rs2295080 and rs2536 polymorphisms within the mTOR gene on cancer risk.Bioscience reports · 2020Article
- Phosphoinositide-3-kinase regulatory subunit 1 gene polymorphisms are associated with schizophrenia and bipolar disorder in the Han Chinese population.Metabolic brain disease · 2020Article
- Deficiency ofOncoTargets and therapy · 2020Article
- Epithelial to Mesenchymal Transition and Cell Biology of Molecular Regulation in Endometrial Carcinogenesis.Journal of clinical medicine · 2019Review
- Article
- Targeting Cyclin D-CDK4/6 Sensitizes Immune-Refractory Cancer by Blocking the SCP3-NANOG Axis.Cancer research · 2018Article
- Association of FGFR2 and PI3KCA genetic variants with the risk of breast cancer in a Chinese population.Cancer management and research · 2018Article
- Impact of phosphoinositide-3-kinase and vitamin D3 nuclear receptor single-nucleotide polymorphisms on the outcome of malignant melanoma patients.Oncotarget · 2017Article
- Polymorphisms of insulin receptor substrate 2 are putative biomarkers for pediatric medulloblastoma: considering the genetic susceptibility and pathological diagnoses.Nagoya journal of medical science · 2017Article
- MicroRNA-Related Polymorphisms in PI3K/Akt/mTOR Pathway Genes Are Predictive of Limited-Disease Small Cell Lung Cancer Treatment Outcomes.BioMed research international · 2017Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe phosphatidylinositol 3-kinase (PI3K)/PTEN/AKT/mTOR and Ras/Raf/MEK/ERK pathways have been implicated in endometrial tumorigenesis. In this candidate pathway analysis, we investigated associations between genetic variations in these two pathways and both risk and clinical outcomes of endometrial cancer.
methodsWe genotyped a total of 48 potentially functional SNPs in 11 key genes (AKT1, AKT2, AKT3, BRAF, FRAP1, KRAS, PDPK1, PIK3CA, PIK3CB, PIK3R1, and PTEN) with the Sequenom genotyping platform in 115 endometrial cancer patients and 230 cancer-free women to evaluate their associations with risk, survival, and recurrence of endometrial cancer.
resultsWe found the following: (1) PIK3CA rs6443624 and rs9838411 variants either borderline or significantly decreased risk of endometrial cancer in a dominant model (adjusted odds ratio [OR], 0.62; 95% CI, 0.39-1.00 and 0.59; 95% CI, 0.36-0.95, respectively). Furthermore, there was a statistically significant multiplicative interaction (P (int) = 0.036) between these two loci in risk of endometrial cancer. In contrast, the AKT1 rs2498801 genotype significantly increased risk of endometrial cancer (adjusted OR, 1.94; 95% CI, 1.02-3.67 in a recessive model). (2) In Cox regression analyses, three SNPs (PIK3R1 rs1862162, AKT2 rs892119, and PIK3CA rs2699887) showed significant associations with survival of endometrial cancer patients. (3) KRAS rs7312175 and PIK3CA rs6443624 had significant effects on recurrence of endometrial cancer individually and combined in a locus-dosage manner (adjusted P (trend) = 0.003).
conclusionThese results suggest that common genetic variations in these pathways may modulate risk and clinical outcomes of endometrial cancer. Further replication and functional studies are needed to confirm these findings.
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