Pharmacogenomics and Personalized Medicine (May 2022)

Susceptibility of Genetic Variations in Methylation Pathway to Gastric Cancer

  • Xiong M,
  • Pan B,
  • Wang X,
  • Nie J,
  • Pan Y,
  • Sun H,
  • Xu T,
  • Cho WCS,
  • Wang S,
  • He B

Journal volume & issue
Vol. Volume 15
pp. 441 – 448

Abstract

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Mengqiu Xiong,1,* Bei Pan,2,* Xuhong Wang,2 Junjie Nie,1 Yuqin Pan,1 Huiling Sun,1 Tao Xu,1 William CS Cho,3 Shukui Wang,1,4,5 Bangshun He1,4,5 1Clinical Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China; 2Medical College, Southeast University, Nanjing, 210006, People’s Republic of China; 3Department of Clinical Oncology, Queen Elizabeth Hospital, Hongkong SAR, People’s Republic of China; 4Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 5Helicobacter pylori Research Key Laboratory, Nanjing Medical University, Nanjing, 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bangshun He, Email [email protected]: DNA methylation in the CpG island is associated with gastric cancer, genetic variations residue in genes involved in methylation pathway could contribute to the occurrence of gastric cancer. Here, we investigated the association between DNMTs (DNMT1/DNMT3A/DNMT3B), MTHFR genetic variations and gastric cancer risk and patients’ survival.Patients and Methods: We recruited 490 gastric cancer patients and 488 age- and sex-matched healthy controls. The genotypes of the genetic variations were detected by a Mass-array platform. A commercial Helicobacter pylori (H. pylori) immunogold testing kit was used to determine the H. pylori infection.Results: We found that carriers of DNMT1 rs2228612C allele was associated with decreased gastric cancer risk (CT vs. TT: adjusted OR = 0.70, 95% CI = 0.53– 0.94, P = 0.02; CT/CC vs.TT: adjusted OR = 0.73, 95% CI = 0.56– 0.96, P = 0.02). Further stratified analysis showed that DNMT1 rs2228612 CT/CC were associated with a decreased gastric cancer risk in the subgroups of age ≤ 64 years old (adjusted OR = 0.61, 95% CI = 0.41– 0.90, P = 0.01), male (adjusted OR = 0.72, 95% CI = 0.53– 0.98, P = 0.03), negative H. pylori infection (adjusted OR = 0.67, 95% CI = 0.45– 0.98, P = 0.04), tumor stage T3-T4 (adjusted OR = 0.69, 95% CI = 0.51– 0.92, P = 0.01), and non-gastric cardiac adenocarcinoma (NGCA) (adjusted OR = 0.72, 95% CI = 0.54– 0.97, P = 0.03). However, none of the genetic variations of this study was associated with overall survival.Conclusion: We concluded that the DNMT1 rs2228612C genotype is a protective factor for gastric cancer in Han Chinese population.Keywords: DNMTs, MTHFR, genetic variation, gastric cancer

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