Dataset Information

Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population-based prognostic study.

ABSTRACT:

Objective

To identify genetic variants that modify bladder cancer prognosis focusing on genes involved in major biological carcinogenesis processes (apoptosis, proliferation, DNA repair, hormone regulation, immune surveillance, and cellular metabolism), as nearly half of patients with bladder cancer experience recurrences reliable predictors of this recurrent phenotype are needed to guide surveillance and treatment.

Patients and methods

We analysed variant genotypes hypothesised to modify these processes in 563 patients with urothelial-cell carcinoma enrolled in a population-based study of incident bladder cancer conducted in New Hampshire, USA. After diagnosis, patients were followed over time to ascertain recurrence and survival status, making this one of the first population-based studies with detailed prognosis data. Cox proportional hazards regression was used to assess the relationship between single nucleotide polymorphisms (SNPs) and prognosis endpoints.

Results

Patients with aldehyde dehydrogenase 2 (ALDH2) variants had a shorter time to first recurrence (adjusted non-invasive hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.29-2.78). There was longer survival among patients with non-invasive tumours associated with DNA repair X-ray repair cross-complementing protein 4 (XRCC4) heterozygous genotype compared with wild-type (adjusted HR 0.53, 95% CI 0.38-0.74). Time to recurrence was shorter for patients who had a variant allele in vascular cellular adhesion molecule 1 (VCAM1) and were treated with immunotherapy (P interaction < 0.001).

Conclusions

Our analysis suggests candidate prognostic SNPs that could guide personalised bladder cancer surveillance and treatment.

SUBMITTER: Andrew AS

PROVIDER: S-EPMC4533837 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population-based prognostic study.

Andrew Angeline S AS Gui Jiang J Hu Ting T Wyszynski Asaf A Marsit Carmen J CJ Kelsey Karl T KT Schned Alan R AR Tanyos Sam A SA Pendleton Eben M EM Ekstrom Rebecca M RM Li Zhongze Z Zens Michael S MS Borsuk Mark M Moore Jason H JH Karagas Margaret R MR

BJU international 20140326 2

<h4>Objective</h4>To identify genetic variants that modify bladder cancer prognosis focusing on genes involved in major biological carcinogenesis processes (apoptosis, proliferation, DNA repair, hormone regulation, immune surveillance, and cellular metabolism), as nearly half of patients with bladder cancer experience recurrences reliable predictors of this recurrent phenotype are needed to guide surveillance and treatment.<h4>Patients and methods</h4>We analysed variant genotypes hypothesised t ...[more]

PMID: 24666523

Similar Datasets

Project description:BackgroundBladder cancer (BC) is regarded as one of the most fatal cancer around the world. Nevertheless, there still lack of sufficient markers to predict the prognosis of BC patients. Herein, we aim to establish a prognosis predicting signature based on long-noncoding RNA (lncRNA) for the invasive BC patients.MethodsThe lncRNA expression profile was downloaded from The Cancer Genome Atlas (TCGA) database, along with the correlated clinicopathological information. The univariate Cox regression test was employed to screen out the recurrence-free survival (RFS)-related lncRNAs. Then, the LASSO method was conducted to construct the signature based on these RFS-related lncRNA candidates. Genes correlated with these fourteen lncRNAs were extracted from the mRNA expression profile, with the Pearson correlation coefficient?>?0.60 or?<?-?0.40. Subsequently, the Proteomap pathway enrichment analyses were conducted to classify the function of these correlated genes. Furthermore, the multivariate analyses were executed to reveal the independent role of the proposed signature with the clinicopathological features.ResultsWe established an lncRNA-based RFS predicting signature by the LASSO Cox regression test, and proved its usage and stability on both the training and validation cohorts by the Kaplan-Meier and receiver operating characteristic (ROC) curves. Notably, the multivariate Cox regression analysis found that our classifier was an independent indicator for muscle-invasive BC patients rather than sex, age and tumor grade, with higher predictive value than the existing ones. Besides, we did the pathway analyses for these genes that highly correlated with the proposed fourteen lncRNAs, as well as the differentially expressed genes (DEGs) derived from the high-risk vs. low-risk groups, and the recurrence vs. non-recurrence groups, respectively. Notably, these results were consistent, and these genes were mostly enriched in the transcription factors, G protein-coupled receptors, MAPK signaling pathways, which were proved significantly associated with tumor progression and drug resistance.ConclusionsOur results suggested that the fourteen-lncRNA-based RFS predicting signature is an independent indicator for BC patients. Further prospective studies with more samples are needed to verify our findings.

Dataset Information

Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population-based prognostic study.

Objective

Patients and methods

Results

Conclusions

Publications

Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population-based prognostic study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets