Association of the 1236C>T variant of the multidrug resistance 1 gene with esophageal squamous cell carcinoma development and prognosis

Abstract

BackgroundEsophageal squamous cell carcinoma (ESCC) is a common cause of cancer related mortality. There is a growing body of evidence showing an association between genetic variants in the 7q21.12 gene locus and an increased risk of cancer. Here we have explored the association between the 1236C > T; rs1128503 genetic variant of the ABCB1/ MDR1 gene with the development and prognosis of ESCC. MethodData from the computer-based patient records (CPRs) of 10 years (between 2006 and 2014) of the Mashhad University of Medical Sciences were used to identify patients with ESCC. Ninety-three ESCC patients and two hundred and twenty-four healthy subjects were recruited. DNA was extracted and genotyped using a Taq-Man based real-time PCR method. The association of the variant with overall-survival (OS) and progression-free survival (PFS) was analyzed using Kaplan–Meier curves, log-rank tests, and Cox model. ResultsPatients with ESCC had a higher frequency of the C allele compared to the control group with MAF of 1.5. Moreover, 22%, and 56% of cases had TT and TC genotypes, compared to 22% for CC. Patients with TT genotype, versus CC had a higher risk of ESCC (OR: 2.3; 95%CI: 1.08–4.8, P = 0.03), although it was not associated with PFS and OS (e.g., OS of TT genotype: 56.8 ± 6.9 months versus OS of CC genotype: 60.5 ± 5.7 months). ConclusionWe have investigated the relationship between a genetic polymorphism of the ABCB1 gene with clinical outcomes of the ESCC-patients, supporting further studies in a larger, and multi-centre settings followed by functional assays to assess the prognostic value of this emerging marker in esophageal squamous cell carcinoma patients.