Association between PLCE1 rs2274223 A > G polymorphism and cancer risk: proof from a meta-analysis

Abstract

Phospholipase C epsilon 1 (PLCE1) plays an important role in cell growth, differentiation and oncogenesis. An increasing number of individual studies have investigated the association between PLCE1 rs2274223 polymorphism and cancer risk, but the conclusions are inconclusive. To obtain a comprehensive conclusion, we performed a meta-analysis of 22 studies with 13188 cases and 14666 controls. The pooled results indicated that PLCE1 rs2274223 A > G polymorphism was associated with an increased risk of overall cancer (G vs. A: OR = 1.15, 95% CI = 1.06–1.25; GG vs. AA: OR = 1.30, 95% CI = 1.10–1.55; GA vs. AA: OR = 1.18, 95% CI = 1.08–1.30; GG/GA vs. AA: OR = 1.20, 95% CI = 1.08–1.32; GG vs. GA/AA: OR = 1.22, 95% CI = 1.04–1.42). The stratification analysis showed the polymorphism was significantly associated with an increased risk of esophageal squamous cell carcinoma (ESCC) other than gastric cancer (GC), especially among the subgroups of Asian, high quality score, sample size > 1000 and the studies consistent with Hardy-Weinberg equilibrium (HWE). This meta-analysis demonstrated that PLCE1 rs2274223 A > G polymorphism may be associated with increased susceptibility to cancer, especially for ESCC. However, due to the substantial heterogeneities across the studies, the conclusion might be not conclusive that need more studies to confirm.

DNMT1 , DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis

“…Among the 20 studies, 18 studies were for Chinese population (respectively from Jiangsu, Jiangxi, Hebei, Shandong, Jilin and Heilongjiang provinces of China), 1 study was for Iranian population (from Fars and Tork) and another one was for Japanese population (from Hiroshima and Yamaguchi). According to the quality assessment criteria (Table S1), scores of the 13 studies (included in the meta-analysis) were 4–12 and 8 studies were with high quality scores (Xue et al, 2015). The main characteristics of the 13 studies were listed in Table 1.…”

“…The quality of each study was assessed according to the quality assessment criteria (Table S1) (Thakkinstian et al, 2011, Xue et al, 2015), in which the overall quality scores ranged from 0 to 15. Studies with scores ≥ 9 were regarded as high quality studies; otherwise, studies were considered to have a low quality.…”

Evaluation of GWAS-identified SNPs at 6p22 with neuroblastoma susceptibility in a Chinese population

“…For example, most of previous studies conducted among Asians, investigating the association between PLCE1 rs2274223 A>G polymorphism and cancer susceptibility, successfully replicated the findings of the original GWAS in the same race. On the contrary, studies performed among Caucasian and African descents failed to confirm the association of this polymorphism with esophageal squamous cell carcinoma susceptibility [20]. Maris et al [8] performed the first GWAS for neuroblastoma with 1032 neuroblastoma patients and 2043 control subjects of European descent at the discovery stage.…”

The controversial role of phospholipase C epsilon (PLCε) in cancer development and progression

“…Recent studies of Qu et al that included 550 patients with ESCC and 550 control individuals demonstrated that GA genotype of rs10882379 was significantly correlated with decreased ESCC risk, whereas AA genotype of rs829232 was significantly associated with a high ESCC risk in Chinese population as compared to GG genotype 34. In attempt to obtain a more comprehensive conclusion about the possible link between PLCε rs2274223A gene polymorphism and risk of ESCC or GC development, Xue and coauthors conducted a meta-analysis of 22 published studies including 13188 cancer cased and 14666 controls 35. This study concluded that rs2274223A>G correlates with an increased risk of both types of cancer, especially ESCC, However, the authors acknowledge that due to the retrospective character of the most of the data and high heterogeneity across the studies, which is attributed to a small number of participants and ethnic variations, their analysis might not be conclusive and needs the data from additional prospective studies for confirmation 35, One of the further reason for the discrepancy between the Chinese and African GWAS studies is a lower linkage disequilibrium (LD) which is an index of the non-random association between alleles at the different loci.…”

“…In attempt to obtain a more comprehensive conclusion about the possible link between PLCε rs2274223A gene polymorphism and risk of ESCC or GC development, Xue and coauthors conducted a meta-analysis of 22 published studies including 13188 cancer cased and 14666 controls 35. This study concluded that rs2274223A>G correlates with an increased risk of both types of cancer, especially ESCC, However, the authors acknowledge that due to the retrospective character of the most of the data and high heterogeneity across the studies, which is attributed to a small number of participants and ethnic variations, their analysis might not be conclusive and needs the data from additional prospective studies for confirmation 35, One of the further reason for the discrepancy between the Chinese and African GWAS studies is a lower linkage disequilibrium (LD) which is an index of the non-random association between alleles at the different loci. According to this hypothesis, the PLCε SNPs described in the Chinese GWAS studies are not directly associated with carcinogenesis, but rather tagging with a high LD some other SNPs which are driving this association 33…”