Abstract
Background And ObjectiveTwo recent genome-wide association studies have identified a shared susceptibility variation PLCE1 rs2274223 for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). Subsequent case-control studies have reported this association in other populations. However, the findings were controversial and the effect remains undetermined. Our aim is to provide a precise quantification of the association between PLCE1 rs2274223 variation and the risk of ESCC and GCA.MethodsStudies were identified by a literature search in MEDLINE and EMBASE databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association in allele, dominant, recessive, homozygous, and heterozygous models.ResultsTen articles were identified, including 22156 ESCC cases and 28803 controls, 5197 GCA cases and 17613 controls. Overall, PLCE1 rs2274223 G allele (G vs. A: OR=1.26, 95% CI: 1.15-1.39 for ESCC; OR=1.51, 95% CI: 1.35–1.69 for GCA) and its carrier (GG +AG vs. AA: OR = 1.23; 95% CI =1.02-1.49 for ESCC; OR =1.62; 95% CI =1.15-2.29 for GCA) were significantly associated with the risk of ESCC and GCA. In stratified analysis by ethnicity, significant association of PLCE1 rs2274223 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.ConclusionsOur meta-analysis results indicated that PLCE1 rs2274223 G allele significantly contributed to the risk of ESCC and GCA, especially in Chinese population.
Highlights
Esophageal cancer is the eighth most common cancer worldwide, with approximate 482,300 new cases and 406,800 related deaths in 2008 [1], and the incidence of which varies significantly according to geographic locations and ethnicity [2]
Published articles that explored the association of PLCE1 and esophageal squamous cell carcinoma (ESCC) or gastric cardia adenocarcinomas (GCA) in peer-reviewed journals were identified by searching PubMed and Ovid MEDLINE database and ISI Web of Science, Science Citation Index Expanded, and China National Knowledge Infrastructure (CNKI)
Characteristics of studies The main characteristics of the 10 studies included in the meta-analysis were summarized in Table 1, of which 8 and 5 studies reported on ESCC and GCA, respectively
Summary
Esophageal cancer is the eighth most common cancer worldwide, with approximate 482,300 new cases and 406,800 related deaths in 2008 [1], and the incidence of which varies significantly according to geographic locations and ethnicity [2]. In the same highincidence area, only a subset of individuals exposed to the environmental risk factors would develop ESCC or GCA, suggesting a role of genetic variations in ESCC and GCA carcinogenesis. Previous evidences of population genetics and familial aggregation suggested that inherited susceptibility contributed significantly to the high rate of ESCC and GCA in these areas [6,7,8]. Two recent genome-wide association studies have identified a shared susceptibility variation PLCE1 rs2274223 for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). In stratified analysis by ethnicity, significant association of PLCE1 rs2274223 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. Conclusions: Our meta-analysis results indicated that PLCE1 rs2274223 G allele significantly contributed to the risk of ESCC and GCA, especially in Chinese population
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