Autophagic Gene Polymorphisms in Liquid Biopsies and Outcome of Patients with Metastatic Clear Cell Renal Cell Carcinoma

Autophagy has been shown to be involved in cancer development and response to cancer therapy. In this study, genotypes of autophagic genes were analyzed to assess their correlation with the risk of clear cell renal cell carcinoma (ccRCC) and the outcome of patients treated with pazopanib for metastatic ccRCC. Single nucleotide polymorphisms (SNPs)were selected in the following genes: ATG4A (rs7880351), ATG4B (rs6709768), ATG4C (rs2886770, rs6670694, rs6683832), ATG5 (rs9373839, rs3804333, rs490010), ATG16L1 (rs6752107), ATG16L2 (rs10751215) and IRGM (rs10059011). The Kaplan-Meier method and log-rank test were used to evaluate differences between groups. Forty patients with metastatic ccRCC treated with pazopanib were included in the analysis. ATG16L2rs10751215 was significantly less frequent in patients with ccRCC compared to the general population, suggesting its potential protective role, while ATG4Ars7880351, ATG4C rs6670694 and rs6683832 and ATG5 rs490010 were correlated with the progression-free survival (PFS) of patients treated with pazopanib. Our results suggest, for the first time, that autophagic gene SNPs are associated with ccRCC risk and patient outcome.