title: Genetic Variants in the p14ARF/MDM2/TP53 Pathway Are Associated with the Prognosis of Esophageal Squamous Cell Carcinoma Patients Treated with Radical Resection.
abstract: The p14ARF/MDM2/ TP53 pathway is known to play an important role in tumor progression by cell cycle control, although the association between this pathway and the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. In this study, we explored the association between genetic variants in the p14ARF/MDM2/TP53 pathway and prognosis in ESCC patients with radical resection. 124 ESCC patients with radical resection were included in this retrospective study and genotyped using the MassArray method. According to multivariate Cox hazard analysis and multiple testing, the TC/CC genotype of p14ARF rs3814960 was shown to be strongly related to a decreased overall survival (OS) (HR = 2.77, 95% CI: 1.33-5.75, P = 0.006, Pc = 0.030) and disease-free survival (DFS) (HR = 2.45, 95% CI: 1.30-4.61, P = 0.005, Pc = 0.025). Moreover, patients with the DEL/A +AA genotype of MDM2 rs34886328 had a notably increased OS (HR = 0.27, 95% CI: 0.13-0.56, P = 4.7×10-4, Pc = 0.003) and DFS (HR = 0.22, 95% CI: 0.11-0.43, P = 1.1×10-5, Pc = 6.6×10-5). We also found that these two SNPs had a cumulative effect on the prognosis of ESCC, with the OS (P < 0.001) and DFS (P < 0.001) being shortest for patients carrying both of these unfavorable genotypes. In conclusion, genetic variants of the p14ARF/MDM2/TP53 pathway are significantly related to OS and DFS, and may be predictors of the prognosis of ESCC after surgery. We speculate the individuals with the TC/CC genotype of p14ARF rs3814960 and/or the DEL/DEL genotype of MDMD2 rs34886328 should have more aggressive treatment and may greatly benefit from early prediction and prevention of an unfavorable prognosis by genotyping before the initiation of therapy. These findings should be further validated in a larger population.
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004947:Esophagus / Q000473:pathology / Q000601:surgery*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012189:Retrospective Studies; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2