Agenetic variant in cdkn2a/2b locus was associated with poor prognosis in patients with esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is among the leading causes of cancer related death.Despite extensive efforts in identifying valid cancer prognostic biomarkers, only a very small numberof markers have been identified. Several genetic variants in the 9p21 region have been identified that are associated with the risk of multiple cancers. Here we explored the association of two genetic variantin the 9p21 region, CDKN2A/B, rs10811661 and rs1333049 for the first time in 273 subjects with, or without ESCC. Data in computer-based patient records (CPRs) of Mashhad University of Medical Sciences were used to retrieve ESCC patients, seen between July 2004 to September 2013. One hundred and twenty one ESCC patients and two hunderd and eight healthy subjects were recruited. DNA was extracted, followed by genotyping. Overall survival (OS) and progression-free survival (PFS) curves were analyzed by Kaplan–Meier method, and compared using log-rank tests. The significantprognostic variables in the univariate analysis were included in multivariate analyses, using a Cox model. We observed that patients with ESCC had a higher frequency of a TT genotype for rs10811661than individuals in the control group, and this polymorphism was also associated with tumor size. Moreover a CC genotype for the rs1333049 polymorphism was associated with a reduced OS of patients with ESCC. In particular, patients with a CC (rs1333049) genotype had a significantly shorter OS (CC genotype: 34.5±8.9 months, vs. CG+GG: 47.7±5.9 months; p value= 0.03). We have shown that the association of a novel genetic variant in CDKN2B gene with clinical outcome of ESCC patients. Further investigations are warranted in a larger population to explore the value of emerging markers as a risk stratification marker in ESCC.

Keywords:

Cancer Prevention , Gene and Cancer , Cell and Cancer , Cancer Genetics , Solid Tumors