Genetic variants in DNA repair predicts the survival of patients with esophageal cancer.

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.

journal_name

Ann Surg

journal_title

Annals of surgery

authors

Lee JM,Yang PW,Yang SY,Chuang TH,Tung EC,Chen JS,Huang PM,Lee YC

doi

10.1097/SLA.0b013e318216f374

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

918-27

issue

5

eissn

0003-4932

issn

1528-1140

pii

00000658-201105000-00012

journal_volume

253

pub_type

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