Functional Polymorphisms Associated with Disease-Free Survival in Resected Carcinoma of the Esophagus

PURPOSE: The aim of this study was to determine whether clinical outcome after surgical resection of esophageal adenocarcinoma (EAC) or esophageal squamous cell carcinoma (ESCC) could be predicted by functional polymorphisms in different proto-oncogenes and tumor suppressor genes. EXPERIMENTAL DESIGN: Six single nucleotide polymorphisms (SNPs) in the AURKA (rs2273535), ERBB2 (rs1136201), MDM2 (rs2279744), CDH1 (rs5030625), CDKN2A (rs11515), and TP73 (rs2273953) genes were genotyped in a consecutive cohort of 346 esophageal cancer patients, who had underwent surgical resection with curative intent. Associations with disease-free survival (DFS) were analyzed with Kaplan–Meier curves and Cox regression, adjusting for potential confounders. RESULTS: Univariate analysis showed no significant associations between the tested polymorphisms and DFS in patients with EAC or ESCC. However, in a multivariate analysis, patients with EAC carrying the heterozygous MDM2 (rs2279744) T/G genotype had significantly improved DFS compared with patients carrying the wild-type genotype (adjusted hazard ratio (AHR), 0.63; 95% confidence interval (CI) [0.45–0.88]). Patients with EAC harboring the homozygous CDH1 (rs5030625) GA/GA genotype had a significantly reduced survival as compared with patients carrying the wild-type genotype AHR 4.0, 95% CI [1.4–11]. CONCLUSIONS: In a large cohort of esophageal cancer patients, the MDM2 T/G and CDH1 GA/GA genotype confer risk of death in patients with EAC. These data suggest that inter-individual differences in germ-line DNA have an impact on DFS in patients with EAC.