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- Title
Single nucleotide polymorphism rs13042395 in the SLC52A3 gene as a biomarker for regional lymph node metastasis and relapse-free survival of esophageal squamous cell carcinoma patients.
- Authors
Hua-Zhen Tan; Zhi-Yong Wu; Jian-Yi Wu; Lin Long; Ji-Wei Jiao; Yu-Hui Peng; Yi-Wei Xu; Shan-Shan Li; Wei Wang; Jian-Jun Zhang; En-Min Li; Li-Yan Xu; Tan, Hua-Zhen; Wu, Zhi-Yong; Wu, Jian-Yi; Long, Lin; Jiao, Ji-Wei; Peng, Yu-Hui; Xu, Yi-Wei; Li, Shan-Shan
- Abstract
<bold>Background: </bold>SLC52A3 was recently identified as a susceptibility gene for esophageal squamous cell carcinoma (ESCC). However, associations between the single nucleotide polymorphisms (SNPs) rs13042395 (C > T) and rs3746803 (G > A) in SLC52A3 and risk, tumor characteristics and survival of ESCC patients remain inconclusive and of unknown prognostic significance.<bold>Methods: </bold>Analyses of the association between SNPs in SLC52A3 and ESCC risk were performed on 479 ESCC cases, together with 479 controls, in a case-control study. Blood samples for cases and controls were collected and genotyped by real-time polymerase chain reaction (PCR) using TaqMan assays. Among the 479 ESCC cases, 343 cases with complete clinical data were used to investigate the association between SNPs and ESCC clinical characteristics; 288 cases with complete clinical data and 5-year follow-up data were used to analyze the association between SNPs and prognosis. Dual luciferase reporter assays and electrophoretic mobility shift assays (EMSAs) were used to investigate the biological function of rs13042395.<bold>Results: </bold>No association was found between SLC52A3 rs3746803 and susceptibility, tumor characteristics or survival of ESCC patients. For rs13042395, TT genotype carriers were likely to have reduced lymph node metastasis (odds ratio (OR) = 0.55, 95 % confidence interval (CI), 0.31-0.98) and longer relapse-free survival time (P = 0.03) . Also, both rs13042395 (hazard ratio (HR) = 0.62, 95 % CI, 0.38-0.99) and regional lymph node metastasis (HR = 2.06, 95 % CI, 1.36-3.13 for N1 vs. N0; HR = 2.88, 95 % CI, 1.70-4.86 for N2 vs. N0; HR = 2.08, 95 % CI, 1.01-4.30 for N3 vs. N0) were independent factors affecting relapse-free survival for ESCC patients who underwent surgery. Dual luciferase reporter assays and EMSAs suggested that the CC genotype of rs13042395 enhanced SLC52A3 expression, probably via binding with specific transcription factors.<bold>Conclusions: </bold>The rs13042395 polymorphism in SLC52A3 is associated with regional lymph node metastasis and relapse-free survival in ESCC patients.
- Subjects
ESOPHAGEAL cancer patients; SINGLE nucleotide polymorphisms; LYMPH node cancer; BLOOD testing; POLYMERASE chain reaction; CANCER relapse; CELL lines; DISEASE susceptibility; ESOPHAGEAL tumors; GENES; GENETIC polymorphisms; GENETICS; METASTASIS; MULTIVARIATE analysis; PROGNOSIS; SQUAMOUS cell carcinoma; KAPLAN-Meier estimator; MEMBRANE transport proteins; GENOTYPES
- Publication
BMC Cancer, 2016, Vol 16, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-016-2588-3