An insertion/deletion polymorphism within the proximal promoter of EGLN2 is associated with susceptibility for gastric cancer in the Chinese population.

Gastric cancer (GC) is among the most common human malignancies and the second leading cause of cancer-related death worldwide. Accumulated evidence from molecular genetics indicates that an individual's genetic factors are involved in their susceptibility to GC. Hypoxia is a common feature of cancer and the hypoxia-inducible factor (HIF), a transcription factor that regulates oxygen homeostasis, plays key roles in the growth of solid tumors and regulating cellular responses to hypoxia. Prolyl hydroxylase (PHD1, also known as EGLN2) is one of the three enzymes capable of hydroxylating the alpha subunit of HIF and results in polyubiquitinylation and proteasomal degradation of HIF. A case-control study, including 415 GC patients and 830 healthy controls, was conducted to investigate the association between GC susceptibility with a 4-bp insertion/deletion polymorphism (rs10680577) in the proximal promoter of EGLN2. Logistic regression analysis showed that the heterozygote and the homozygote 4-bp del/del confer a significantly increased risk of GC after controlling for other covariates (adjusted odds ratio [OR]=1.35, 95% confidence interval [CI] 1.05-1.75, p=0.017; OR=2.19, 95% CI 1.15-4.18, p=0.009, respectively). Carriage of the 4-bp deletion allele was associated with a greatly increased risk of developing the disease (OR=1.38, 95% CI 1.12-1.70, p=0.002). Moreover, stratification analysis showed that the association was more prominent in smokers (adjusted OR=2.09, 95% CI=1.40-3.12, p for heterogeneity=0.01). Our data suggested that common genetic polymorphisms in EGLN2 may influence GC risk in the Chinese population. Considering the relative small sample size, replication in other populations with a larger sample size and further functional analysis are required for fully understanding the roles of EGLN2 polymorphisms in predisposition for GC.