Abstract
A SNP in MET is associated with increased risk of recurrence of renal-cell carcinoma.
Major finding: A SNP in MET is associated with increased risk of recurrence of renal-cell carcinoma.
Approach: SNPs in genes implicated in RCC pathogenesis were assessed in discovery and validation cohorts.
Impact: This SNP may be a prognostic marker and may aid design of adjuvant trials of MET inhibitors.
The risk of tumor recurrence after surgery in patients with renal-cell carcinoma (RCC) is modulated in part by tumor grade and stage, but biomarkers of this risk have not been identified. Single-nucleotide polymorphisms (SNP) have been linked to increased risk of developing RCC, and association of SNPs with patient survival has been reported in other cancers. To investigate whether genetic polymorphisms are also associated with risk of tumor relapse in patients with RCC, Schutz and colleagues evaluated germline DNA samples from patients with histologically confirmed localized RCC. Seventy genes that have been reported to play a role in RCC pathogenesis were selected for analysis. An initial discovery cohort of 403 patients who were prospectively followed after nephrectomy was used for genotyping of 290 SNPs, which were evaluated for association with recurrence-free survival; of these, 12 SNPs were subsequently validated in an independent cohort of 151 patients. Intriguingly, a synonymous polymorphism (rs11762213) in exon 2 of MET, which encodes for the hepatocyte growth factor receptor, was significantly associated with increased risk of tumor recurrence or death after adjusting for clinical and pathologic variables. Patients in the discovery cohort with 1 or 2 copies of the polymorphic allele exhibited a shorter recurrence-free survival (19 months vs 50 months for patients not carrying the risk allele) and a decrease in 5-year recurrence-free survival (19% vs 46%). In addition, the MET polymorphism was associated with a higher risk of disease recurrence and with reduced overall survival in the second patient cohort. Although further validation and mechanistic studies of how this SNP enhances risk are necessary, these findings identify this polymorphism as a candidate biomarker for relapse risk in RCC and suggest that MET inhibitors may benefit patients carrying this SNP.
RSS Feeds