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.
Pooled analyses suggested that PLCE1 rs2274223 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.
Results of subgroup analysis showed that the rs2274223 polymorphism was associated with higher risk for esophageal cancer and gastric cancer relative to colorectal cancer and head and neck cancer.
The PLCE1 rs2274223 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.
Eight single nucleotide polymorphisms (SNPs), rs465498, rs17728461, rs4488809, rs753955, rs13361707, rs9841504, rs2274223, and rs13042395, were reported by genome wide association studies (GWASs) to be closely related to the susceptibility of lung cancer (LC), gastric cancer (GC) or esophageal cancer (EC) in Han population from northern or southern China.
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).
Gene-environment interaction analysis presented a best model consisted of four factors (rs2274223, rs2274224, family history, and smoking) with testing balance accuracy (TBA): 0.66 and cross validation consistency (CVC): 7/10, which could increase the esophageal cancer risk in the "high risk group" with 3.67-fold (OR: 3.67, 95% CI: 2.74-4.92), compared to the "low risk group".
A single-nucleotide polymorphism (rs2274223: A5780G:His1927Arg) in the phospholipase C epsilon gene (PLCϵ) was recently identified as a susceptibility locus for esophageal cancer in Chinese subjects.
Stratified analyses indicated a significantly increased risk of eso</span>pha</span>geal cancer associated with the PLCE1 rs2274223</span> AG genotype was more evident among females, younger patients and never drinkers, compared with the PLCE1 r</span>s2274223 AA genotypes.
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).