A sequence variant in the phospholipase C epsilon C2 domain is associated with esophageal carcinoma and esophagitis. Issue 1 (6th February 2013)

• Record Type: Journal Article
• Authors: Wang, Li‐Dong; Bi, Xiuli; Song, Xin; Pohl, Nicole M.; Cheng, Yulan; Zhou, Yixing; Shears, Stephen; Ansong, Emmanuel; Xing, Mengtao; Wang, Shaomeng; Xu, Xiao‐Chun; Huang, Peng; Xu, Liyan; Wang, Liang; Fan, Zongmin; Zhao, Xueke; Dong, Huali; Meltzer, Stephen J.; Ding, Ivan; Yang, Wancai; Angel, Joe
• Is Part Of: Molecular carcinogenesis. Volume 52:Issue 1(2013:Jan.)
• Page Start: 80
• Page End: 86
• Publication Date: 2013-02-06
• Subjects: Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22016
• Languages: English
• ISSNs: 0899-1987

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="mc22016-sec-0001" sec-type="section"> <p>A single‐nucleotide polymorphism (rs2274223: A5780G:His1927Arg) in the phospholipase C epsilon gene (<italic>PLCϵ</italic>) was recently identified as a susceptibility locus for esophageal cancer in Chinese subjects. To determine the underlying mechanisms of <italic>PLCϵ</italic> and this SNP in esophageal carcinogenesis, we analyzed PLC<italic>ϵ</italic> 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 <italic>PLCϵ</italic> 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; <italic>P</italic> = 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.</p> </sec> </abstract>