Germline Genetic Variations at 11q13 and 12p11 Locus Modulate Age at Onset for Renal Cell Carcinoma
Résumé
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.
Mots clés
ITPR2
PCR
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
renal cell carcinoma
risk
single nucleotide polymorphism
RCC
SNP
angiotensinogen
body mass index
AGT
BMI
EPAS1
GWAS
statistical analysis
Signal processing
classification