Germline Genetic Variations at 11q13 and 12p11 Locus Modulate Age at Onset for Renal Cell Carcinoma
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
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