Genetic variants in DNA repair predicts the survival of patients with esophageal cancer
Journal
Annals of Surgery
Journal Volume
253
Journal Issue
5
Pages
918-927
ISBN
21490450
Date Issued
2011
Author(s)
Abstract
Objective: To investigate the association of the genetic variants in excision repair cross-complementation group 2 (ERCC2) R156R and ERCC4 rs3136038 with survival duration for patients with esophageal cancer. Background: ERCC2 and ERCC4 are important molecules participating nucleotide excision repair system. The clinical relevance of the genetic variants of these genes is largely unknown currently. Patients and Methods: A total of 400 patients with a diagnosis of esophageal cancer were included. The genetic variants in the promoter regions of ERCC2 on R156R and ERCC4 on rs3136038 were analyzed with the TaqMan assay from leukocyte DNA collected before treatment and correlated to survival of the patients. Results: Presence with ERCC2 R156R C/C or ERCC4 rs3136038 C/T genotype of the patients could additively increase risk of death and disease progression. Under multivariate analysis, T, N staging and simultaneous presentation of these unfavorable genotypes were found significant for prognosis (P < 0.05). Accumulation of each unfavorable genotype would associate with adjusted HRs [95% CI] of 1.35 [1.10-1.65] and 1.37 [1.12-1.68] (P ? 0.05) for death and disease progression respectively. The prognostic impact of these genotypes were more evident in the subgroup of patients with early disease status including T staging (II or less), free from lymph node metastasis or being able to undergo surgical resection (P < 0.05 for both overall and disease progression-free survival duration, respectively). Conclusion: Genetic variants in ERCC2 and ERCC4 may provide further survival prediction in addition to TNM staging system of esophageal cancer, which is more evident in the patients with early disease status. ? 2011 Lippincott Williams & Wilkins.
SDGs
Other Subjects
transcription factor; transcription factor ercc4; unclassified drug; xeroderma pigmentosum group D protein; adult; aged; article; cancer growth; cancer mortality; cancer staging; cancer surgery; cancer survival; Chinese; DNA polymorphism; DNA repair; esophagus cancer; female; genetic variability; genotype; human; lymph node metastasis; major clinical study; male; priority journal; prognosis; promoter region; Adult; Aged; China; Cohort Studies; Confidence Intervals; Disease Progression; DNA Repair; DNA-Binding Proteins; Esophageal Neoplasms; Female; Genetic Predisposition to Disease; Genetic Variation; Humans; Male; Middle Aged; Polymorphism, Genetic; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Assessment; Sensitivity and Specificity; Survival Analysis; Xeroderma Pigmentosum Group D Protein
Type
journal article