Joint Effects Between CDKN2B/P15 Methylation and Environmental Factors on the Susceptibility to Gastric Cancer.

BACKGROUND: The incidence of gastric cancer has long been at a high level in China, seriously affecting the health of Chinese people.

AIMS: This case‒control study was performed to identify gene methylation biomarkers of gastric cancer susceptibility.

METHODS: A total of 393 gastric cancer cases and 397 controls were included in this study. Gene methylation in peripheral blood leukocytes was detected by a methylation-sensitive high-resolution melting method, and the Helicobacter pylori antibody presence was semi-quantified in serum by ELISA.

RESULTS: Individuals with total methylation of CDKN2B/P15 had a 1.883-fold (95%CI: 1.166-3.040, P = 0.010) risk of gastric cancer compared with unmethylated individuals. Individuals with both CDKN2B/P15 and NEUROG1 methylation had a higher risk of gastric cancer (OR = 2.147, 95% CI: 1.137-4.073, P = 0.019). The interaction between CDKN2B/P15 and NEUROG1 total methylation on gastric cancer risk was affected by the pattern of adjustment. In addition, the joint effects between CDKN2B/P15 total methylation and environmental factors, such as freshwater fish intake (OR = 6.403, 95% CI = 2.970-13.802, P < 0.001), irregular diet (OR = 5.186, 95% CI = 2.559-10.510, P < 0.001), unsanitary water intake (OR = 2.238, 95% CI = 1.144-4.378, P = 0.019), smoking (OR = 2.421, 95% CI = 1.456-4.026, P = 0.001), alcohol consumption(OR = 2.163, 95% CI = 1.309-3.576, P = 0.003), and garlic intake(OR = 0.373, 95% CI = 0.196-0.709, P = 0.003) on GC risk were observed, respectively. However, CDKN2B/P15 and NEUROG1 total methylation were not associated with gastric cancer prognosis.

CONCLUSION: CDKN2B/P15 methylation in peripheral blood may be a potential biomarker for evaluating susceptibility to gastric cancer. The joint effects between CDKN2B/P15 methylation and environmental factors may also contribute to gastric cancer susceptibility.