In:
Molecular Carcinogenesis, Wiley, Vol. 52, No. S1 ( 2013-11), p. 80-86
Abstract:
A single‐nucleotide polymorphism (rs2274223: A5780G:His1927Arg) in the phospholipase C epsilon gene ( PLCϵ ) was recently identified as a susceptibility locus for esophageal cancer in Chinese subjects. To determine the underlying mechanisms of PLCϵ and this SNP in esophageal carcinogenesis, we analyzed PLC ϵ genotypes, expression, and their correlation in esophageal cancer cell lines, non‐transformed esophageal cells, 58 esophageal squamous cell carcinomas and 10,614 non‐cancer subjects from China. We found that the G allele (AG or GG) was associated with increased PLCϵ mRNA and protein expression in esophageal cancer tissues and in esophageal cancer cell lines. G allele was also associated with higher enzyme activity, which might be associated with increased protein expression. Quantitative analysis of the C2 domain sequences revealed that A:G allelic imbalance was strongly linked to esophageal malignancy. Moreover, the analysis of 10,614 non‐cancer subjects demonstrated that the G allele was strongly associated with moderate to severe esophagitis in the subjects from the high‐incidence areas of China (OR 6.03, 95% CI 1.59–22.9 in high‐incidence area vs. OR 0.74, 95% CI 0.33–1.64 in low‐incidence area; P = 0.008). In conclusion, the PLCϵ gene, particularly the 5780G allele, might play a pivotal role in esophageal carcinogenesis via upregulating PLCϵ mRNA, protein, and enzyme activity, and augmenting inflammatory process in esophageal epithelium. Thus, 5780G allele may constitute a promising biomarker for esophageal squamous cell carcinoma risk stratification, early detection, and progression prediction. © 2013 Wiley Periodicals, Inc.
Type of Medium:
Online Resource
ISSN:
0899-1987
,
1098-2744
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2001984-1
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