Susceptibility of Genetic Variations in Methylation Pathway to Gastric Cancer

Background: 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 variatio...

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Bibliographic Details
Published in:Pharmacogenomics and personalized medicine 2022-05, Vol.15, p.441
Main Authors: Xiong, Mengqiu, Pan, Bei, Wang, Xuhong, Nie, Junjie, Pan, Yuqin, Sun, Huiling, Xu, Tao, Cho, William C.S, Wang, Shukui, He, Bangshun
Format: Article
Language:English
Subjects:
Analysis
Disease susceptibility
Genes
Genetic aspects
Health aspects
Helicobacter infections
Methylation
Methyltransferases
Stomach cancer
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Summary:Background: 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 [less than or equal to]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
ISSN:1178-7066
1178-7066
DOI:10.2147/PGPM.S340911