The Survival Impact of XPA and XPC Genetic Polymorphisms on Patients with Esophageal Squamous Cell Carcinoma

Abstract

The purpose of this study was to investigate the association between survival outcome of esophageal cancer patients and the genetic variants in xeroderma pigmentosum groups A (XPA) and C (XPC), 2 important molecules in the nucleotide excision pathway for DNA repair. A total of 501 patients with a diagnosis of esophageal squamous cell carcinoma (ESCC) were enrolled in the study. The genetic variants of XPA in 5'UTR and those of XPC at exon 15 K939Q were analyzed with the TaqMan assay from the genomic DNA of peripheral leukocytes and correlated to the posttreatment survival outcome. Patients with XPA 5'UTR A/G and XPC K939Q C/C genotypes were found to be imposed with a higher risk of mortality after treatment compared with patients with wild-type homozygous genotypes [adjusted HR (95 % CI) of death being 1.36 (1.06-1.74) and 1.34 (0.97-1.83), respectively]. Cox's multivariate analysis detected a statistically significant increased trend in risk of mortality with the accumulation of any of these 2 unfavorable genotypes compared with patients with other genotypes [adjusted HR (95 % CI) = 1.29 (1.08-1.53), P = .005]. The effect was more pronounced in the population treated with esophagectomy (P = .023) and undergoing concurrent neoadjuvant chemoradiotherapy (CCRT) (P = .002). The hereditary genetic variants in XPA and XPC can serve as independent predictors of the clinical outcome of patients with ESCC, especially in those who are treated with esophagectomy and undergo chemoradiation.