ArticlePloS one2013
Discovery analysis of TCGA data reveals association between germline genotype and survival in ovarian cancer patients.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 38 citations in OpenAlex.
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- Genome-wide association and functional interrogation identified a variant at 3p26.1 modulating ovarian cancer survival among Chinese women.Cell discovery · 2021Article
- Identification of crucial long non-coding RNAs and mRNAs along with related regulatory networks through microarray analysis in esophageal carcinoma.Functional & integrative genomics · 2021Article
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- Comprehensive analysis of the lncRNA‑associated competing endogenous RNA network in breast cancer.Oncology reports · 2019Article
- Gene-gene interaction network analysis of hepatocellular carcinoma using bioinformatic software.Oncology letters · 2018Article
- Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients.International journal of cancer · 2018Article
- C10orf116 Gene Copy Number Loss in Prostate Cancer: Clinicopathological Correlations and Prognostic Significance.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Characterization of potential driver mutations involved in human breast cancer by computational approaches.Oncotarget · 2017Review
- Meta-dimensional data integration identifies critical pathways for susceptibility, tumorigenesis and progression of endometrial cancer.Oncotarget · 2016Article
- CrossHub: a tool for multi-way analysis of The Cancer Genome Atlas (TCGA) in the context of gene expression regulation mechanisms.Nucleic acids research · 2016Article
- Abnormal methylation status of FBXW10 and SMPD3, and associations with clinical characteristics in clear cell renal cell carcinoma.Oncology letters · 2015Article
- Combined PTEN Mutation and Protein Expression Associate with Overall and Disease-Free Survival of Glioblastoma Patients.Translational oncology · 2014Article
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8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundOvarian cancer remains a significant public health burden, with the highest mortality rate of all the gynecological cancers. This is attributable to the late stage at which the majority of ovarian cancers are diagnosed, coupled with the low and variable response of advanced tumors to standard chemotherapies. To date, clinically useful predictors of treatment response remain lacking. Identifying the genetic determinants of ovarian cancer survival and treatment response is crucial to the development of prognostic biomarkers and personalized therapies that may improve outcomes for the late-stage patients who comprise the majority of cases.
methodsTo identify constitutional genetic variations contributing to ovarian cancer mortality, we systematically investigated associations between germline polymorphisms and ovarian cancer survival using data from The Cancer Genome Atlas Project (TCGA). Using stage-stratified Cox proportional hazards regression, we examined >650,000 SNP loci for association with survival. We additionally examined whether the association of significant SNPs with survival was modified by somatic alterations.
resultsGermline polymorphisms at rs4934282 (AGAP11/C10orf116) and rs1857623 (DNAH14) were associated with stage-adjusted survival (p= 1.12e-07 and 1.80e-07, FDR q= 1.2e-04 and 2.4e-04, respectively). A third SNP, rs4869 (C10orf116), was additionally identified as significant in the exome sequencing data; it is in near-perfect LD with rs4934282. The associations with survival remained significant when somatic alterations.
conclusionsDiscovery analysis of TCGA data reveals germline genetic variations that may play a role in ovarian cancer survival even among late-stage cases. The significant loci are located near genes previously reported as having a possible relationship to platinum and taxol response. Because the variant alleles at the significant loci are common (frequencies for rs4934282 A/C alleles = 0.54/0.46, respectively; rs1857623 A/G alleles = 0.55/0.45, respectively) and germline variants can be assayed noninvasively, our findings provide potential targets for further exploration as prognostic biomarkers and individualized therapies.
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