So, we aimed to replicate association of two previously reported non-synonymous polymorphisms (rs2274223A>G and rs3765524C>T) from haplotype block 10 and evaluated a novel variant (rs7922612C>T) from haplotype block 2 of PLCE1 with susceptibility and prognosis of ESCC in northern Indian population.
In this meta-analysis, the PLCE1 rs2274223 polymorphism was confirmed to have a statistically significant association with an increasing risk of ESCC and gastric cancer.
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).
Consistent with the previous study, loci at rs2074356 and rs2274223 could increase the risk of ESCC, furthermore, there were significant interactions between HPV sero-status and the susceptibility loci on the risk of ESCC.
Our meta-analysis results indicated that PLCE1 rs2274223 G allele significantly contributed to the risk of ESCC and GCA, especially in Chinese population.
In conclusion, PLCE1 rs2274223 polymorphism may be used as a potential biomarker for DTC susceptibility particularly for ESCC and GCA in the Chinese population.
These results highlighted the role of a genetic factor in ESCC and suggested that the PLCε1 rs2274223 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.
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.
This meta-analysis demonstrated that PLCE1 rs2274223 A > G polymorphism may be associated with increased susceptibility to cancer, especially for ESCC.
SNP rs2274223 was independently associated with increased risk of ESCC (adjusted odds ratio [OR], 2.80; 95% confidence interval [95% CI], 1.45-5.39 for GG vs. AA), and SNP rs2274224 was found to be associated with decreased risk of ESCC (adjusted OR, 0.65; 95% CI, 0.46-0.91 for CG vs. CC).
To the best of our knowledge, this is the first study to report an association between rs2274223 and rs4072037 and the risk of oesophageal squamous cell carcinoma in a Caucasian population.
We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case-control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.
In contrast to the modulation of the risk of ESCC in Asians, it is unlikely that the PLCE1 rs2274223 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 PLCE1 rs2274223, 10 variants were rated as moderate, and 18 variants were rated as weak.
We genotyped five PLCE1 variants in cases and controls, and found association of Arg548Leu (rs17417407) with a reduced risk of OSCC (OR = 0.74, 95% CI = 0.60-0.93, P = 0.008) in the Black population.
In the present study, we validated this finding and also explored the risk of ESCC associated with other two unreported potentially functional SNPs (rs17417407 G>T and rs2274224 C>G) of PLCE1 in a population-based case-control study to investigate the association between these three potentially functional SNPs in PLCE1 and susceptibility to ESCC.
To evaluate the association between the single nucleotide polymorphisms (SNPs) in PLCE1 gene and ESCC risk, a case-control study including 550 patients with ESCC and 550 age, gender-matched controls was carried out to investigate the genetic susceptibility of three SNPs (rs3765524 C/T and two unreported potentially functional SNPs rs10882379 G/A and rs829232 G/A) as well as the interactions of gene-gene and gene-environment in the development of ESCC.
So, we aimed to replicate association of two previously reported non-synonymous polymorphisms (rs2274223A>G and rs3765524C>T) from haplotype block 10 and evaluated a novel variant (rs7922612C>T) from haplotype block 2 of PLCE1 with susceptibility and prognosis of ESCC in northern Indian population.
SNP rs2274223 was independently associated with risk of ESCC (adjusted odds ratio [OR], 1.49; 95% confidence interval [95% CI], 1.03-2.17 for GG vs AA), and SNP rs11187870 was also found to be associated with risk of ESCC assuming a dominant model (adjusted OR, 1.20; 95% CI, 1.00-1.44 for CG/CC vs GG).
We found that only 4 SNPs (rs753724, rs11187842, rs2274223, and rs12263737) with moderate linkage disequilibrium (LD) confer significantly increased risk of ESCC, with the ORs ranging from 1.43 to 2.04, and there was a risk allele dose-dependent increase in ESCC risk (P-trend=0.043).