Pooled analyses suggested that PLCE1rs2274223 variant was significantly correlated with the likelihood of esophageal cancer (dominant model: p < 0.001, OR = 0.77, 95% CI 0.72-0.83; recessive model: p < 0.001, OR = 1.28, 95% CI 1.12-1.45; additive model: p < 0.001, OR = 1.20, 95% CI 1.11-1.29; allele model: p < 0.001, OR = 0.80, 95% CI 0.74-0.88) and gastric cancer (recessive model: p = 0.001, OR = 1.27, 95% CI 1.10-1.47; allele model: p = 0.03, OR = 0.88, 95% CI 0.78-0.98) in overall population.
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.
The PLCE1rs2274223 polymorphism has a relationship with family history of esophageal cancer, but does not have any significant association with age, gender, smoking, alcohol drinking, food hygiene, eating habits, living around the environment and occupation in cases.
Overall, we determined that PLCE1 expression was associated with tumor progression in both esophageal cancers (pooled OR=5.93; 95%CI=3.86 to 9.11) and gastric cancers (pooled OR=9.73; 95%CI=6.46 to 14.7).
However, three genome-wide association studies of esophageal cancer have identified a shared susceptibility locus at 10q23 (rs2274223: A5780G) in phospholipase C epsilon 1 (PLCE1).
Stratified analyses indicated a significantly increased risk of esophageal cancer associated with the PLCE1rs2274223 AG genotype was more evident among females, younger patients and never drinkers, compared with the PLCE1 rs2274223 AA genotypes.
Association between novel PLCE1 variants identified in published esophageal cancer genome-wide association studies and risk of squamous cell carcinoma of the head and neck.