sábado, 12 de mayo de 2018

Germline Mutations in DNA Repair Genes are Associated with Bladder Cancer Risk and Unfavorable Prognosis. - PubMed - NCBI

Germline Mutations in DNA Repair Genes are Associated with Bladder Cancer Risk and Unfavorable Prognosis. - PubMed - NCBI



 2018 May 4. doi: 10.1111/bju.14370. [Epub ahead of print]

Germline Mutations in DNA Repair Genes are Associated with Bladder Cancer Risk and Unfavorable Prognosis.

Na R1,2,3Wu Y1,2Jiang G1Yu H2Lin X1Wang M4Conran CA2Fantus RJ2,5Zhang N1Liu S1Helfand BT2Zheng SL2Isaacs WB6,7Ding Q1Shen Z1Xu J1,2.

Abstract

OBJECTIVES:

Germline DNA repair gene mutations in bladder cancer (BCa) are poorly characterized. We therefore sought to perform a systematic evaluation of whether these mutations are associated with increased risk of BCa and aggressive disease.

MATERIALS AND METHODS:

Germline DNA from 98 BCa patients was analyzed for 54 DNA repair genes using a customized targeted sequencing panel. Population control data were obtained from the public databases Exome Aggregation Consortium database (ExAC) and Genome Aggregation Database (gnomAD). Mutation pathogenicity was annotated based on American College of Medical Genetics (ACMG) criteria, mutation frequencies in the general population and the ClinVar database. Mutation frequencies were compared based on case-control and case-case designs for disease risks, disease aggressiveness and outcomes.

RESULTS:

The frequency of pathogenic/likely pathogenic germline DNA repair gene mutations was 10.20% among BCa patients. Within the subset of subjects with muscle invasive bladder cancer (MIBC), the frequency was 15.8%, ~2.4-fold higher than subjects with non-muscle invasive bladder cancer (6.67%, NMIBC). The mutation frequency among subjects with early onset disease (<45 yr) was ~3-fold higher than those diagnosed after age ≥45 yr (28.57% vs. 8.79%). Mutation carriers had a significantly higher frequency of unfavorable clinical outcomes (disease recurrence or progression to metastatic BCa) than non-carriers (50.00% vs. 13.64%, P=0.013).

CONCLUSION:

Pathogenic and likely pathogenic mutations in DNA repair genes were associated with unfavorable prognosis of the disease. This article is protected by copyright. All rights reserved.

KEYWORDS:

Bladder cancer; DNA repair genes; germline; mutation

PMID:
 
29727914
 
DOI:
 
10.1111/bju.14370

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