PURPOSE: To investigate the association between the prognosis of patients with esophageal squamous cell carcinoma (ESCC) and the autophagy or collagen related single nucleotide polymorphisms (SNPs).

PATIENTS AND METHODS: The study was analyzed retrospectively. A total of 570 patients diagnosed with ESCC were enrolled in the study and randomly assigned to a training set (n=188) or replication set (n=382). The genotypes of 16 candidate SNPs involved in autophagy or collagen-related functions were analyzed using iPLEX Gold technology from the genomic DNA of peripheral leukocytes. The association of the genotypes and the overall survival or progression-free survival of patients was analyzed by multivariate Cox regression analysis and Kaplan-Meier survival function.

RESULTS: Among these subjects, 239 patients were with early stage (stage IIa or earlier), and 331 patients were with advanced stages (stage IIb or advanced). In patients with early stages, the genetic variants of ATG5:rs1322178, ATG5:rs3804329 and COL4A3: rs28381984 was associated with increased risk of death in the training set. The associations were confirmed in the replication set and in the combined set (HR[95 % CI]=2.47 [1.31-4.65], P=0.005 in ATG5:rs1322178; HR[95 % CI]=2.16[1.08-4.31], P=0.029 in ATG5:rs3804329; HR[95 % CI]=1.48[1.00-2.20], P=0.052 in COL4A3: rs28381984, in combined set). In cumulative effect analysis of multiple SNPs, patients carrying the unfavorable genotypes at all these 3 genes exhibited a 3.87 fold increasd risk of death in early ESCC patients (HR[95 % CI]=3.87 [1.37-10.93], P=0.011). Finally, the Kaplan-Meier survival curves were constructed for overall survival by the number of unfavorable genotypes. The overall survival duration differed significantly between those with 0, 1, 2, and 3 cumulative unfavorable genotypes (log-rank P=0.012).

CONCLUSION: The hereditary genetic polymorphisms of ATG5 and COL4A3 genes can serve as prognostic predictors of the patients with early ESCC.

Citation Format: Jang-Ming Lee, Pei-Wen Yang, Tzu-Hsuan Chiang, Ya-Chuan Huang, Ching-Yueh Hsieh. The genetic polymorphisms of ATG5 and COL4A3 are associated with the prognosis of patients with esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2859. doi:10.1158/1538-7445.AM2014-2859