Abstract 3991: The genetic variants of growth factor-related genes associate with the prognosis of patients with advanced esophageal squamous cell carcinoma .
Authors: Lee Jang-Ming , Yang Pei-Wen , Huang Ya-Chuan , Hsieh Min-Shu , Hsieh Ching-Yueh , Huang Pei-Ming , Hsu Hsao-Hsun , Chen Jin-Shing , Kuo Shuenn-Wen 
Published: August 2014

PURPOSE: To investigate the association between the genetic polymorphisms of growth factor-related genes and the prognosis of patients with advanced esophageal squamous cell carcinoma (ESCC).

PATIENTS AND METHODS: A total of 336 ESCC patients with advanced tumor stages (stage 2b+3+4) were enrolled in the study. These subjects were randomly assigned to a training set (n=95) and a replication set (n=241).The genotypes of candidate single nucleotide polymorphism (SNPs) were analyzed using iPLEX Gold technology from the genomic DNA of peripheral leukocytes, and were correlated with the clinical outcome of patients in training, replication, and combined groups. Serum levels of growth factors were examined by enzyme-link immunosorbent assay (ELISA).

RESULTS: In training group, the genotyping of 16 candidate SNPs was successfully performed. Seven SNPs, rs4444903, rs2010963, rs2272037, rs713646, rs3025039, rs3025040, rs2016347, significant or borderline significant correlated with mortality or disease progression and were further evaluated in an independent replication group. In replication group, GG of rs4444903 at EGF gene and CC of rs2010903 at VEGF showed unfavorable trend for the mortality (P=0.286 for rs4444903; P=0.215 for rs2010963). These 2 SNPs showed significant effects on overall survival of the patients in combing group (GG vs. AA, adjusted [HR] = 1.29, 95% CI=1.01-1.66, P=0.045 for rs4444903; CC vs. GG, adjusted [HR] = 1.53, 95% CI=1.07-2.18, P=0.020 for rs2010963). Meanwhile, GA genotype of rs2272037at IGF1R gene also show unfavorable trend among all subjects (GA vs. GG, [HR] = 1.24, 95% CI=0.96-1.60, P=0.108). Combing these 3 SNPs, patients with 3 unfavorable genotypes showed 2-fold risk for mortality compared to patients without any of the unfavorable genotypes (accumulated unfavorable genotypes 3 vs. 0, [HR] = 2.00, 95% CI=1.10-3.64, P=0.023). Additionally, GG genotype of EGF_rs4444903 correlated with increase serum levels of EGF in patients with advanced ESCC. Finally, both EGF and VEGF expression levels significant associated with the mortality of patients.

CONCLUSION: The genetic variants in growth factor-related can serve as prognostic predictors of the patients with advanced ESCC, and thus provide more information for the personalized therapies for the patients with ESCC.

Citation Format: Jang-Ming Lee, Pei-Wen Yang, Ya-Chuan Huang, Min-Shu Hsieh, Ching-Yueh Hsieh, Pei-Ming Huang, Hsao-Hsun Hsu, Jin-Shing Chen, Shuenn-Wen Kuo. The genetic variants of growth factor-related genes associate with the prognosis of patients with advanced esophageal squamous cell carcinoma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3991. doi:10.1158/1538-7445.AM2013-3991