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Published in: Gastric Cancer 2/2021

01-03-2021 | Helicobacter Pylori | Original Article

Promising aberrant DNA methylation marker to predict gastric cancer development in individuals with family history and long-term effects of H. pylori eradication on DNA methylation

Authors: Hee Jin Kim, Nayoung Kim, Hyoung Woo Kim, Ji Hyun Park, Cheol Min Shin, Dong Ho Lee

Published in: Gastric Cancer | Issue 2/2021

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Abstract

Objective

It remains unknown whether individuals with a family history (FH) of gastric cancer (GC) are associated with aberrant DNA methylation. The aim of this study was to investigate the association between aberrant DNA methylation and FH of GC.

Design

Using quantitative MethyLight assay, MOS, miR124a-3, NKX6-1, EMX1, CDH1, and TWIST1 methylation levels in the noncancerous gastric mucosa was compared between subjects with and without FH based on GC and Helicobacter pylori (Hp) infection. Changes in the methylation levels were evaluated over time after Hp eradication.

Results

In Hp-positive GC patients, MOS (P < 0.001), CDH1 (P < 0.001), and TWIST1 (P = 0.004) methylation were decreased in subjects with FH (n = 64) than in those without FH (n = 58). In Hp-positive controls, MOS methylation was lower in subjects with FH (n = 73) than in those without FH (n = 50) (P = 0.042), while miR124a-3 (P = 0.006), NKX6-1 (P < 0.001), and CDH1 (P < 0.001) methylation were higher in subjects with FH. CDH1 methylation constantly decreased from 2 years in GC patients and 3–4 years in controls after Hp eradication (all P < 0.001). A persistent decrease in methylation over time was not observed in other genes after eradication.

Conclusion

The methylation of MOS and CDH1 provided an association between aberrant DNA methylation and gastric carcinogenesis in FH of GC, a useful marker for GC risk in individuals with FH. Furthermore, CDH1 methylation decreased after Hp eradication.
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Literature
1.
go back to reference Ushijima T. Epigenetic field for cancerization. J Biochem Mol Biol. 2007;40:142–50.PubMed Ushijima T. Epigenetic field for cancerization. J Biochem Mol Biol. 2007;40:142–50.PubMed
2.
go back to reference Ushijima T, Sasako M. Focus on gastric cancer. Cancer Cell. 2004;5:121–5.CrossRef Ushijima T, Sasako M. Focus on gastric cancer. Cancer Cell. 2004;5:121–5.CrossRef
3.
go back to reference Chan AO, Lam SK, Wong BC, Wong WM, Yuen MF, Yeung YH, et al. Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer. Gut. 2003;52:502–6.CrossRef Chan AO, Lam SK, Wong BC, Wong WM, Yuen MF, Yeung YH, et al. Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer. Gut. 2003;52:502–6.CrossRef
4.
go back to reference Niwa T, Tsukamoto T, Toyoda T, Mori A, Tanaka H, Maekita T, et al. Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Res. 2010;70:1430–40.CrossRef Niwa T, Tsukamoto T, Toyoda T, Mori A, Tanaka H, Maekita T, et al. Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Res. 2010;70:1430–40.CrossRef
5.
go back to reference Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M, et al. High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res. 2006;12:989–95.CrossRef Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M, et al. High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res. 2006;12:989–95.CrossRef
6.
go back to reference Shin CM, Kim N, Jung Y, Park JH, Kang GH, Park WY, et al. Genome-wide DNA methylation profiles in noncancerous gastric mucosae with regard to Helicobacter pylori infection and the presence of gastric cancer. Helicobacter. 2011;16:179–88.CrossRef Shin CM, Kim N, Jung Y, Park JH, Kang GH, Park WY, et al. Genome-wide DNA methylation profiles in noncancerous gastric mucosae with regard to Helicobacter pylori infection and the presence of gastric cancer. Helicobacter. 2011;16:179–88.CrossRef
7.
go back to reference Shin CM, Kim N, Jung Y, Park JH, Kang GH, Kim JS, et al. Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis. Cancer Sci. 2010;101:1337–466.CrossRef Shin CM, Kim N, Jung Y, Park JH, Kang GH, Kim JS, et al. Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis. Cancer Sci. 2010;101:1337–466.CrossRef
8.
go back to reference Leung WK, Man EP, Yu J, Go MY, To KF, Yamaoka Y, et al. Effects of Helicobacter pylori eradication on methylation status of E-cadherin gene in noncancerous stomach. Clin Cancer Res. 2006;12:3216–21.CrossRef Leung WK, Man EP, Yu J, Go MY, To KF, Yamaoka Y, et al. Effects of Helicobacter pylori eradication on methylation status of E-cadherin gene in noncancerous stomach. Clin Cancer Res. 2006;12:3216–21.CrossRef
9.
go back to reference Perri F, Cotugno R, Piepoli A, Merla A, Quitadamo M, Gentile A, et al. Aberrant DNA methylation in non-neoplastic gastric mucosa of H. pylori infected patients and effect of eradication. Am J Gastroenterol. 2007;102:1361–71.CrossRef Perri F, Cotugno R, Piepoli A, Merla A, Quitadamo M, Gentile A, et al. Aberrant DNA methylation in non-neoplastic gastric mucosa of H. pylori infected patients and effect of eradication. Am J Gastroenterol. 2007;102:1361–71.CrossRef
10.
go back to reference Nakajima T, Enomoto S, Yamashita S, Ando T, Nakanishi Y, Nakazawa K, et al. Persistence of a component of DNA methylation in gastric mucosae after Helicobacter pylori eradication. J Gastroenterol. 2010;45:37–44.CrossRef Nakajima T, Enomoto S, Yamashita S, Ando T, Nakanishi Y, Nakazawa K, et al. Persistence of a component of DNA methylation in gastric mucosae after Helicobacter pylori eradication. J Gastroenterol. 2010;45:37–44.CrossRef
11.
go back to reference Yaghoobi M, Bijarchi R, Narod SA. Family history and the risk of gastric cancer. Br J Cancer. 2010;102:237–42.CrossRef Yaghoobi M, Bijarchi R, Narod SA. Family history and the risk of gastric cancer. Br J Cancer. 2010;102:237–42.CrossRef
12.
go back to reference Oliveira C, Pinheiro H, Figueiredo J, Seruca R, Carneiro F. Familial gastric cancer: genetic susceptibility, pathology, and implications for management. Lancet Oncol. 2015;16:e60–70.CrossRef Oliveira C, Pinheiro H, Figueiredo J, Seruca R, Carneiro F. Familial gastric cancer: genetic susceptibility, pathology, and implications for management. Lancet Oncol. 2015;16:e60–70.CrossRef
13.
go back to reference Shin CM, Kim N, Yang HJ, Cho SI, Lee HS, Kim JS, et al. Stomach cancer risk in gastric cancer relatives: interaction between Helicobacter pylori infection and family history of gastric cancer for the risk of stomach cancer. J Clin Gastroenterol. 2010;44:e34–e3939.CrossRef Shin CM, Kim N, Yang HJ, Cho SI, Lee HS, Kim JS, et al. Stomach cancer risk in gastric cancer relatives: interaction between Helicobacter pylori infection and family history of gastric cancer for the risk of stomach cancer. J Clin Gastroenterol. 2010;44:e34–e3939.CrossRef
14.
go back to reference Choi YJ, Kim N, Jang W, Seo B, Oh S, Shin CM, et al. Familial clustering of gastric cancer: a retrospective study based on the number of first-degree relatives. Medicine. 2016;95:e3606.CrossRef Choi YJ, Kim N, Jang W, Seo B, Oh S, Shin CM, et al. Familial clustering of gastric cancer: a retrospective study based on the number of first-degree relatives. Medicine. 2016;95:e3606.CrossRef
15.
go back to reference El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000;404:398–402.CrossRef El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000;404:398–402.CrossRef
16.
go back to reference Kim HJ, Kwon M, Kim N, Lee JB, Won S. The influence of family history on stage and survival of gastric cancer according to the TGFB1 C-509T polymorphism in Korea. Gut Liver. 2020;14:79–88.CrossRef Kim HJ, Kwon M, Kim N, Lee JB, Won S. The influence of family history on stage and survival of gastric cancer according to the TGFB1 C-509T polymorphism in Korea. Gut Liver. 2020;14:79–88.CrossRef
17.
go back to reference Yoon H, Kim N, Shin CM, Lee HS, Kim BK, Kang GH, et al. Risk factors for metachronous gastric neoplasms in patients who underwent endoscopic resection of a gastric neoplasm. Gut liver. 2016;10:228–36.CrossRef Yoon H, Kim N, Shin CM, Lee HS, Kim BK, Kang GH, et al. Risk factors for metachronous gastric neoplasms in patients who underwent endoscopic resection of a gastric neoplasm. Gut liver. 2016;10:228–36.CrossRef
18.
go back to reference Shin CM, Kim N, Lee HS, Park JH, Ahn S, Kang GH, et al. Changes in aberrant DNA methylation after Helicobacter pylori eradication: a long-term follow-up study. Int J Cancer. 2013;133:2034–42.CrossRef Shin CM, Kim N, Lee HS, Park JH, Ahn S, Kang GH, et al. Changes in aberrant DNA methylation after Helicobacter pylori eradication: a long-term follow-up study. Int J Cancer. 2013;133:2034–42.CrossRef
19.
go back to reference Maeda M, Nakajima T, Oda I, Shimazu T, Yamamichi N, Maekita T, et al. High impact of methylation accumulation on metachronous gastric cancer: 5-year follow-up of a multicentre prospective cohort study. Gut. 2017;66:1721–3.CrossRef Maeda M, Nakajima T, Oda I, Shimazu T, Yamamichi N, Maekita T, et al. High impact of methylation accumulation on metachronous gastric cancer: 5-year follow-up of a multicentre prospective cohort study. Gut. 2017;66:1721–3.CrossRef
20.
go back to reference Kaise M, Yamasaki T, Yonezawa J, Miwa J, Ohta Y, Tajiri H. CpG island hypermethylation of tumor-suppressor genes in H. pylori-infected non-neoplastic gastric mucosa is linked with gastric cancer risk. Helicobacteria. 2008;13:35–41.CrossRef Kaise M, Yamasaki T, Yonezawa J, Miwa J, Ohta Y, Tajiri H. CpG island hypermethylation of tumor-suppressor genes in H. pylori-infected non-neoplastic gastric mucosa is linked with gastric cancer risk. Helicobacteria. 2008;13:35–41.CrossRef
21.
go back to reference Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117:927–39.CrossRef Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117:927–39.CrossRef
22.
go back to reference Puisieux A, Valsesia-Wittmann S, Ansieau S. A twist for survival and cancer progression. Br J Cancer. 2006;94:13–7.CrossRef Puisieux A, Valsesia-Wittmann S, Ansieau S. A twist for survival and cancer progression. Br J Cancer. 2006;94:13–7.CrossRef
23.
go back to reference Kokkola A, Kosunen TU, Puolakkainen P, Sipponen P, Harkonen M, Laxen F, et al. Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis. APMIS. 2003;111:619–24.CrossRef Kokkola A, Kosunen TU, Puolakkainen P, Sipponen P, Harkonen M, Laxen F, et al. Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis. APMIS. 2003;111:619–24.CrossRef
24.
go back to reference Trinh BN, Long TI, Laird PW. DNA methylation analysis by MethyLight technology. Methods. 2001;25:456–62.CrossRef Trinh BN, Long TI, Laird PW. DNA methylation analysis by MethyLight technology. Methods. 2001;25:456–62.CrossRef
25.
go back to reference Ando T, Yoshida T, Enomoto S, Asada K, Tatematsu M, Ichinose M, et al. DNA methylation of microRNA genes in gastric mucosae of gastric cancer patients: its possible involvement in the formation of epigenetic field defect. Int J Cancer. 2009;124:2367–74.CrossRef Ando T, Yoshida T, Enomoto S, Asada K, Tatematsu M, Ichinose M, et al. DNA methylation of microRNA genes in gastric mucosae of gastric cancer patients: its possible involvement in the formation of epigenetic field defect. Int J Cancer. 2009;124:2367–74.CrossRef
26.
go back to reference Nanjo S, Asada K, Yamashita S, Nakajima T, Nakazawa K, Maekita T, et al. Identification of gastric cancer risk markers that are informative in individuals with past H. pylori infection. Gastric Cancer. 2012;15:382–8.CrossRef Nanjo S, Asada K, Yamashita S, Nakajima T, Nakazawa K, Maekita T, et al. Identification of gastric cancer risk markers that are informative in individuals with past H. pylori infection. Gastric Cancer. 2012;15:382–8.CrossRef
27.
go back to reference Kang GH, Lee S, Cho NY, Gandamihardja T, Long TI, Weisenberger DJ, et al. DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis. Lab Invest. 2008;88:161–70.CrossRef Kang GH, Lee S, Cho NY, Gandamihardja T, Long TI, Weisenberger DJ, et al. DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis. Lab Invest. 2008;88:161–70.CrossRef
28.
go back to reference Shin CM, Kim N, Park JH, Kang GH, Kim JS, Jung HC, et al. Prediction of the risk for gastric cancer using candidate methylation markers in the non-neoplastic gastric mucosae. J Pathol. 2012;226:654–65.CrossRef Shin CM, Kim N, Park JH, Kang GH, Kim JS, Jung HC, et al. Prediction of the risk for gastric cancer using candidate methylation markers in the non-neoplastic gastric mucosae. J Pathol. 2012;226:654–65.CrossRef
29.
go back to reference Kim JJ, Chung SW, Kim JH, Kim JW, Oh JS, Kim S, et al. Promoter methylation of helicase-like transcription factor is associated with the early stages of gastric cancer with family history. Ann Oncol. 2006;17:657–62.CrossRef Kim JJ, Chung SW, Kim JH, Kim JW, Oh JS, Kim S, et al. Promoter methylation of helicase-like transcription factor is associated with the early stages of gastric cancer with family history. Ann Oncol. 2006;17:657–62.CrossRef
30.
go back to reference Chang ZW, Dong L, Qin YR, Song M, Guo HY, Zhu QL. Correlations between gastric cancer family history and ROBO2 and RASSF2A gene methylations. J Cancer Res Ther. 2016;12:597–600.CrossRef Chang ZW, Dong L, Qin YR, Song M, Guo HY, Zhu QL. Correlations between gastric cancer family history and ROBO2 and RASSF2A gene methylations. J Cancer Res Ther. 2016;12:597–600.CrossRef
31.
go back to reference Kang GH, Shim YH, Jung HY, Kim WH, Ro JY, Rhyu MG. CpG island methylation in premalignant stages of gastric carcinoma. Cancer Res. 2001;61:2847–51.PubMed Kang GH, Shim YH, Jung HY, Kim WH, Ro JY, Rhyu MG. CpG island methylation in premalignant stages of gastric carcinoma. Cancer Res. 2001;61:2847–51.PubMed
32.
go back to reference Choi IJ, Kook MC, Kim YI, Cho SJ, Lee JY, Kim CG, et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med. 2018;378:1085–95.CrossRef Choi IJ, Kook MC, Kim YI, Cho SJ, Lee JY, Kim CG, et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med. 2018;378:1085–95.CrossRef
33.
go back to reference Michigami Y, Watari J, Ito C, Nakai K, Yamasaki T, Kondo T, et al. Long-term effects of H. pylori eradication on epigenetic alterations related to gastric carcinogenesis. Sci Rep. 2018;8:14369.CrossRef Michigami Y, Watari J, Ito C, Nakai K, Yamasaki T, Kondo T, et al. Long-term effects of H. pylori eradication on epigenetic alterations related to gastric carcinogenesis. Sci Rep. 2018;8:14369.CrossRef
34.
go back to reference Kristensen LS, Hansen LL. PCR-based methods for detecting single-locus DNA methylation biomarkers in cancer diagnostics, prognostics, and response to treatment. Clin Chem. 2009;55:1471–83.CrossRef Kristensen LS, Hansen LL. PCR-based methods for detecting single-locus DNA methylation biomarkers in cancer diagnostics, prognostics, and response to treatment. Clin Chem. 2009;55:1471–83.CrossRef
Metadata
Title
Promising aberrant DNA methylation marker to predict gastric cancer development in individuals with family history and long-term effects of H. pylori eradication on DNA methylation
Authors
Hee Jin Kim
Nayoung Kim
Hyoung Woo Kim
Ji Hyun Park
Cheol Min Shin
Dong Ho Lee
Publication date
01-03-2021
Publisher
Springer Singapore
Published in
Gastric Cancer / Issue 2/2021
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-020-01117-w

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