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Gastric Mucosal Atrophy Impedes Housekeeping Gene Methylation in Gastric Cancer Patients
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Jung-Hwan Oh, Mun-Gan Rhyu, Suk-Il Kim, Mi-Ri Yun, Jung-Ha Shin, Seung-Jin Hong
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Cancer Res Treat. 2019;51(1):267-279. Published online April 30, 2018
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DOI: https://doi.org/10.4143/crt.2018.085
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 Abstract
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- Purpose
Helicobacter pylori infection induces phenotype-stabilizing methylation and promotes gastric mucosal atrophy that can inhibit CpG-island methylation. Relationship between the progression of gastric mucosal atrophy and the initiation of CpG-island methylation was analyzed to delineate epigenetic period for neoplastic transformation.
Materials and Methods
Normal-appearing gastric mucosa was biopsied from 110 H. pylori–positive controls, 95 H. pylori–negative controls, 99 gastric cancer patients, and 118 gastric dysplasia patients. Gastric atrophy was assessed using endoscopic-atrophic-border score. Methylation-variable sites of eight CpG-island genes adjacent to Alu (CDH1, ARRDC4, PPARG, and TRAPPC2L) or LTR (MMP2, CDKN2A, RUNX2, and RUNX3) retroelements and stomach-specific TFF3 gene were analyzed using radioisotope-labeled methylation-specific polymerase chain reaction.
Results
Mean ages of H. pylori–positive controls with mild, moderate, and severe atrophy were 51, 54, and 65 years and those of H. pylori–associated TFF3 overmethylation at the three atrophic levels (51, 58, and 63 years) tended to be periodic. Alu-adjacent overmethylation (50 years) was earlier than TFF3 overmethylation (58 years) in H. pylori–positive controls with moderate atrophy. Cancer patients with moderate atrophy showed late Alu-adjacent (58 years) overmethylation and frequent LTR-adjacent overmethylation. LTR-adjacent overmethylation was frequent in cancer (66 years) and dysplasia (68 years) patients with severe atrophy.
Conclusion
Atrophic progression is associated with gastric cancer at moderate level by impeding the initiation of Alu-adjacent methylation. LTR-adjacent methylation is increased in cancer patients and subsequently in dysplasia patients.
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Citations
Citations to this article as recorded by  - The global prevalence of gastric cancer in Helicobacter pylori-infected individuals: a systematic review and meta-analysis
Maryam Shirani, Reza Pakzad, Mohammad Hossein Haddadi, Sousan Akrami, Arezoo Asadi, Hossein Kazemian, Melika Moradi, Vahab Hassan Kaviar, Abolfazl Rafati Zomorodi, Saeed Khoshnood, Mahnaz Shafieian, Ronia Tavasolian, Mohsen Heidary, Morteza Saki
BMC Infectious Diseases.2023;[Epub] CrossRef - Periodic Fluctuations in the Incidence of Gastrointestinal Cancer
Mun-Gan Rhyu, Jung-Hwan Oh, Tae Ho Kim, Joon-Sung Kim, Young A Rhyu, Seung-Jin Hong
Frontiers in Oncology.2021;[Epub] CrossRef - Fluoride exposure and CALCA methylation is associated with the bone mineral density of Chinese women
Renjie Sun, Guoyu Zhou, Lihua Liu, Lijun Ren, Yu Xi, Jingyuan Zhu, Hui Huang, Zhiyuan Li, Yan Li, Xuemin Cheng, Yue Ba
Chemosphere.2020; 253: 126616. CrossRef - Periodic Methylation Patterns in the Background Mucosa of Gastric Cancer
Sang-Woong Kim, Jung-Hwan Oh, Tae Ho Kim, Joon-Sung Kim, Seung-Jin Hong
The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2019; 19(1): 48. CrossRef
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