Literature DB >> 23911636

Germline genetic variations at 11q13 and 12p11 locus modulate age at onset for renal cell carcinoma.

François Audenet1, Géraldine Cancel-Tassin2, Pierre Bigot2, Marie Audouin2, Cécile Gaffory2, Valérie Ondet2, Frédéric Thibault2, Karine Auribault2, Stéphane Gazut2, Nora Benhabiles2, Abdel-Rhamène Azzouzi2, Arnaud Méjean2, Morgan Rouprêt2, Olivier Cussenot2.   

Abstract

PURPOSE: Few risk factors have been identified for renal cell carcinoma. We performed a validation study in a population with a European background to identify the most significant variants previously identified in association with renal cell carcinoma risk.
MATERIALS AND METHODS: We performed a case-control validation study after recruiting 463 controls and 463 patients with a histologically confirmed diagnosis of clear cell renal cell carcinoma. For each patient and matched control we genotyped 8 single nucleotide polymorphisms selected from previous studies to evaluate the association between candidate single nucleotide polymorphisms and renal cell carcinoma susceptibility.
RESULTS: After adjusting for patient age, gender, smoking status and body mass index the AG + AA genotypes from rs7105934 (11q13) were associated with a decreased risk of renal cell carcinoma (OR 0.50, 95% CI 0.33-0.75, p = 0.001) and the AC + CC genotypes from rs1049380 (ITPR2) were associated with an increased risk (OR 1.66, 95% CI 1.28-2.16, p <0.001). Kidney cancer developed at an older age in patients carrying the dominant risk allele A for rs7105934 (mean age at diagnosis 73.1 vs 68.9 years, p = 0.002) and at a younger age in those carrying the dominant allele C for rs1049380 (mean 68.1 vs 70.8 years, p = 0.005).
CONCLUSIONS: In what is to our knowledge the first validation study of the main 8 single nucleotide polymorphism variants associated with renal cell carcinoma susceptibility we confirmed the association of 2 single nucleotide polymorphisms with the risk of renal cell carcinoma. Each variant influenced patient age at disease diagnosis.
Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Entities:  

Keywords:  AGT; BMI; EPAS1; GWAS; ITPR2; PCR; RCC; SNP; angiotensinogen; body mass index; carcinoma; ccRCC; clear cell RCC; endothelial PAS domain protein 1; genetic; genome-wide association study; genotype; inositol 1,4,5-triphosphate receptor, type 2; kidney; polymerase chain reaction; polymorphism; renal cell; renal cell carcinoma; risk; single nucleotide polymorphism

Mesh:

Year:  2013        PMID: 23911636     DOI: 10.1016/j.juro.2013.07.064

Source DB:  PubMed          Journal:  J Urol        ISSN: 0022-5347            Impact factor:   7.450


  7 in total

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