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

François Audenet; Géraldine Cancel-Tassin; Pierre Bigot; Marie Audouin; Cécile Gaffory; Valérie Ondet; Frédéric Thibault; Karine Auribault; Stéphane Gazut; Nora Benhabiles; Abdel-Rhamène Azzouzi; Arnaud Méjean; Morgan Rouprêt; Olivier Cussenot

doi:10.1016/j.juro.2013.07.064

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

J Urol. 2014 Feb;191(2):487-92. doi: 10.1016/j.juro.2013.07.064. Epub 2013 Aug 1.

Affiliations

¹ Centre de Recherche pour les Pathologies Prostatiques (FA, GC-T, PB, MA, CG, VO, FT, ARA, MR, OC), Paris, France; Academic Department of Urology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (MR), Université Pierre et Marie Curie (Université Paris 06), Paris, France; ONCOTYPE-Uro (FA, GC-T, MA, CG, VO, MR, OC), Université Pierre et Marie Curie (Université Paris 06), Paris, France; ER 2 (FA, GC-T, MA, FT, KA, OC), Université Pierre et Marie Curie (Université Paris 06), Paris, France; Academic Department of Urology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris Descartes, University Paris V (FA, AM), Paris, France; Academic Department of Urology, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Groupement Hospitalier Universitaire Est (CG, VO, OC), Paris, France; Centre Hospitalier Universitaire d'Angers, Academic Department of Urology (PB, ARA), Angers, France; Sensors Signal and Information Processing Department, Information Models and Learning Laboratory, CEA LIST Institute, Saclay, France. Electronic address: francois.audenet@gmail.com.
² Centre de Recherche pour les Pathologies Prostatiques (FA, GC-T, PB, MA, CG, VO, FT, ARA, MR, OC), Paris, France; Academic Department of Urology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (MR), Université Pierre et Marie Curie (Université Paris 06), Paris, France; ONCOTYPE-Uro (FA, GC-T, MA, CG, VO, MR, OC), Université Pierre et Marie Curie (Université Paris 06), Paris, France; ER 2 (FA, GC-T, MA, FT, KA, OC), Université Pierre et Marie Curie (Université Paris 06), Paris, France; Academic Department of Urology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris Descartes, University Paris V (FA, AM), Paris, France; Academic Department of Urology, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Groupement Hospitalier Universitaire Est (CG, VO, OC), Paris, France; Centre Hospitalier Universitaire d'Angers, Academic Department of Urology (PB, ARA), Angers, France; Sensors Signal and Information Processing Department, Information Models and Learning Laboratory, CEA LIST Institute, Saclay, France.

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

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.

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 terms

Age of Onset*
Aged
Body Mass Index
Carcinoma, Renal Cell / epidemiology*
Carcinoma, Renal Cell / genetics*
Case-Control Studies
Chromosomes, Human, Pair 11 / genetics*
Female
Genetic Predisposition to Disease / genetics*
Genetic Variation*
Humans
Kidney Neoplasms / epidemiology*
Kidney Neoplasms / genetics*
Male
Middle Aged
Multivariate Analysis
Polymorphism, Single Nucleotide / genetics*
Risk Factors
White People / genetics