Association between EPHA5 methylation status in peripheral blood leukocytes and the risk and prognosis of gastric cancer

Altered DNA methylation, genetic alterations, and environmental factors are involved in tumorigenesis. As a tumor suppressor gene, abnormal methylation was found in gastric cancer (GC) tissues and was linked to the initiation, progression and prognosis of GC. In this study, the methylation level in peripheral blood leukocytes (PBLs) was detected to explore its relationship with GC risk and prognosis. A total of 366 GC cases and 374 controls were selected as the subjects of this study to collect their environmental factors, and the methylation status was detected through the methylation-sensitive high-resolution melting method. Logistic regression analysis was utilized to evaluate the associations among methylation, environmental factors and GC risk. Meanwhile, the propensity score (PS) was used to adjust the imbalance of some independent variables. After PS adjustment, Pm (positive methylation) was more likely to increase the GC risk than Nm (negative methylation) (OR = 1.827, 95% CI [1.202-2.777], = 0.005). Pm had a more significant association with GC risk in the elderly (OR = 2.785, 95% CI [1.563-4.961], = 0.001) and -negative groups (OR = 2.758, 95% CI [1.369-5.555], = 0.005). Moreover, the combined effects of Pm and infection (OR = 3.543, 95% CI [2.233-5.621], < 0.001), consumption of alcohol (OR = 2.893, 95% CI [1.844-4.539], < 0.001), and salty food intake (OR = 4.018, 95% CI [2.538-6.362], < 0.001) on increasing the GC risk were observed. In addition, no convincing association was found between Pm and the GC prognosis. methylation in PBLs and its combined effects with environmental risk factors are related to the GC risk.