6 research outputs found
Aberrant DNA Methylation Links Cancer Susceptibility Locus 15q25.1 to Apoptotic Regulation and Lung Cancer
Quantitative Analysis of DNA Methylation Profiles in Lung Cancer Identifies Aberrant DNA Methylation of Specific Genes and Its Association with Gender and Cancer Risk Factors
Model based survival function by categories of circulating vitamin B6 and stage.
<p>Estimates derived from flexible parametric survival models assuming proportional hazards for B6 categories, no interaction between stage and B6 categories, and a diagnosis age of 60y.</p
Hazard ratios (HR) and 95% confidence intervals (CI) for a doubling in vitamin B6 concentration by potential effect modifiers.
<p>Estimates derived from Cox models stratified by country of recruitment, and adjusted for stage, age at recruitment, and sex. <i>p</i>-values are from Wald tests of the interaction terms. A separate estimate for Romania is not provided due to an insufficient number of observations.</p
Circulating Concentrations of Vitamin B6 and Kidney Cancer Prognosis: A Prospective Case-Cohort Study
Application of Genomic Sequencing to Refine Patient Stratification for Adjuvant Therapy in Renal Cell Carcinoma
International audiencePurpose: Patients with resected localized clear-cell renal cell carcinoma (ccRCC) remain at variable risk of recurrence. Incorporation of biomarkers may refine risk prediction and inform adjuvant treatment decisions. We explored the role of tumor genomics in this setting, leveraging the largest cohort to date of localized ccRCC tissues subjected to targeted gene sequencing. Experimental Design: The somatic mutation status of 12 genes was determined in 943 ccRCC cases from a multinational cohort of patients, and associations to outcomes were examined in a Discovery (n = 469) and Validation (n = 474) framework. Results: Tumors containing a von-Hippel Lindau (VHL) mutation alone were associated with significantly improved outcomes in comparison with tumors containing a VHL plus additional mutations. Within the Discovery cohort, those with VHL+0, VHL+1, VHL+2, and VHL+≥3 tumors had disease-free survival (DFS) rates of 90.8%, 80.1%, 68.2%, and 50.7% respectively, at 5 years. This trend was replicated in the Validation cohort. Notably, these genomically defined groups were independent of tumor mutational burden. Amongst patients eligible for adjuvant therapy, those with a VHL+0 tumor (29%) had a 5-year DFS rate of 79.3% and could, therefore, potentially be spared further treatment. Conversely, patients with VHL+2 and VHL+≥3 tumors (32%) had equivalent DFS rates of 45.6% and 35.3%, respectively, and should be prioritized for adjuvant therapy. Conclusions: Genomic characterization of ccRCC identified biologically distinct groups of patients with divergent relapse rates. These groups account for the ∼80% of cases with VHL mutations and could be used to personalize adjuvant treatment discussions with patients as well as inform future adjuvant trial design