An Association and Meta-Analysis of Esophageal Squamous Cell Carcinoma Risk Associated with PLCE1rs2274223, C20orf54 rs13042395 and RUNX1 rs2014300 Polymorphisms.
A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus in genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) that share similar risk factors with SCCHN.
Our findings suggested that genetic variants in PLCE1 might serve as candidate markers for Kazakh ESCC susceptibility, and these LD variants might influence ESCC risk individually and jointly by promoting the messenger RNA and protein expression of the gene.
In conclusion, PLCE1rs2274223 polymorphism may be used as a potential biomarker for DTC susceptibility particularly for ESCC and GCA in the Chinese population.
Our results further confirmed that genetic variations in PLCE1 may contribute to ESCC risk associated with tobacco exposure in a central Chinese population.
In contrast to the modulation of the risk of ESCC in Asians, it is unlikely that the PLCE1rs2274223 and RFT2 13042395 SNPs play a role in EAC or ESCC susceptibility in Dutch Caucasians.
In additional, five variants on five genes were rated as strong cumulative epidemiological evidence for a nominally significant association with EC and ESCC risk, including CYP1A1 rs1048943, EGF rs444903, HOTAIR rs920778, MMP2 rs243865, and PLCE1rs2274223, 10 variants were rated as moderate, and 18 variants were rated as weak.
Recent large-scale genome-wide association studies (GWAS) reported that functional genetic variations in the phospholipase C epsilon gene (PLCE1) were strongly associated with risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in Chinese population.
These results highlighted the role of a genetic factor in ESCC and suggested that the PLCε1rs2274223 SNP might be an effective genetic marker to assess the risk of ESCC in individuals with a UGIC family history from a region of high incidence in northern China.
In stratified analysis by ethnicity, significant association of PLCE1rs2274223 G allele and the risk of ESCC (OR=1.33, 95% CI 1.21-1.45) and GCA (OR =1.56, 95% CI: 1.47-1.64) was observed in Chinese population.
A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for gastric cancer (P = 8.40 x 10(-9); per-allele odds ratio (OR) = 1.31) and ESCC (P = 3.85 x 10(-9); OR = 1.34).
We genotyped five PLCE1 variants in cases and controls, and found association of rs17417407" genes_norm="51196">Arg548Leu (rs17417407) with a reduced risk of OSCC (OR = 0.74, 95% CI = 0.60-0.93, P = 0.008) in the Black population.
Our study identified and validated that this immunohistochemical biomarker panel of 3 proteins, consisting of PLCE1, IKBα, and p53, is not only independently associated with an unfavorable outcome for ESCC patients but also able to predict disease progression to precancerous lesions.
To our knowledge, this study demonstrates for the first time that PLCE1 overexpression correlates with lymph node metastasis and advanced TNM stages of Kazakh ESCC, implicating a role of PLCE1 in cancer metastasis and aggressiveness in ethnic Kazakh patients with ESCC.