DOI QR코드

DOI QR Code

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

  • Cao, Xue-Yuan (Department of Gastric and Colorectal Surgery, First Hospital of Jilin University) ;
  • Jia, Zhi-Fang (Division of Clinical Epidemiology, First Hospital of Jilin University) ;
  • Cao, Dong-Hui (Division of Clinical Epidemiology, First Hospital of Jilin University) ;
  • Kong, Fei (Division of Clinical Epidemiology, First Hospital of Jilin University) ;
  • Jin, Mei-Shan (Division of Pathology, First Hospital of Jilin University) ;
  • Suo, Jian (Department of Gastric and Colorectal Surgery, First Hospital of Jilin University) ;
  • Jiang, Jing (Division of Clinical Epidemiology, First Hospital of Jilin University)
  • Published : 2013.10.30

Abstract

Background: DNA methyltransferase-3a (DNMT3a) plays significant roles in embryogenesis and the generation of aberrant methylation in carcinogenesis. This study aimed to investigate associations between single nucleotide polymorphisms (SNPs) of the DNMT3a gene and risk of Helicobacter pylori infection, gastric atrophy and gastric cancer. Methods: The subjects comprised 447 patients with gastric cancer; 111 individuals with gastric atrophy and 961 healthy controls. Two SNPs (rs1550117 and rs13420827) of the DNMT3a gene were genotyped by Taqman assay. DNMT3a expression was analyzed in cancer tissues from 89 patients by tissue microarray technique. Odds ratio (ORs) and 95% confidence intervals were calculated by multivariate logistic regression. Results: Among healthy controls, risk of H.pylori infection was significantly higher in subjects with the rs1550117 AA genotype, compared to those with GG/AG genotypes of DNMT3a [OR=2.08, (95%CI: 1.02-4.32)]. However, no significant correlation was found between the two SNPs and risk of developing gastric atrophy or gastric cancer. In addition, no increase in DNMT3a expression was observed in the gastric cancer with H.pylori infection. Conclusions: This study revealed that DNMT3a rs1550117 polymorphism is significantly associated with an increased risk of H. pylori infection, but did not support any evidence for contributions of DNMT3a rs1550117 and rs13420827 to either gastric atrophy or gastric cancer. The biological roles of DNMT3a polymorphisms require further investigation.

Keywords

Polymorphisms;DNA methyltransferase 3a;Helicobacter pylori;gastric atrophy;gastric cancer

Acknowledgement

Supported by : National Natural Science Foundation of China

References

  1. Cao Q, Ran ZH, Xiao SD (2007). Screening of atrophic gastritis and gastric cancer by serum pepsinogen, gastrin-17 and Helicobacter pylori immunoglobulin G antibodies. J Dig Dis, 8, 15-22. https://doi.org/10.1111/j.1443-9573.2007.00271.x
  2. Bray F, Jemal A, Grey N, Ferlay J, Forman D (2012). Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol, 13, 790-801. https://doi.org/10.1016/S1470-2045(12)70211-5
  3. Chuah SK, Tsay FW, Hsu PI, Wu DC (2011). A new look at anti-Helicobacter pylori therapy. World J Gastroenterol, 17, 3971-5. https://doi.org/10.3748/wjg.v17.i35.3971
  4. Cortessis VK, Thomas DC, Levine AJ, et al (2012). Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships. Hum Genet, 131, 1565-89. https://doi.org/10.1007/s00439-012-1189-8
  5. Ding WJ, Fang JY, Chen XY, Peng YS (2008). The expression and clinical significance of DNA methyltransferase proteins in human gastric cancer. Dig Dis Sci, 53, 2083-9. https://doi.org/10.1007/s10620-007-0145-2
  6. Fan H, Liu D, Qiu X, et al (2010). A functional polymorphism in the DNA methyltransferase-3A promoter modifies the susceptibility in gastric cancer but not in esophageal carcinoma. BMC Med, 8, 12. https://doi.org/10.1186/1741-7015-8-12
  7. Guo XB, Guo L, Zhi QM, et al (2011). Helicobacter pylori induces promoter hypermethylation and downregulates gene expression of IRX1 transcription factor on human gastric mucosa. J Gastroenterol Hepatol, 26, 1685-90. https://doi.org/10.1111/j.1440-1746.2011.06808.x
  8. Kamangar F, Dawsey SM, Blaser MJ, et al (2006). Opposing risks of gastric cardia and noncardia gastric adenocarcinomas associated with Helicobacter pylori seropositivity. J Natl Cancer Inst, 98, 1445-52. https://doi.org/10.1093/jnci/djj393
  9. He S, Wang F, Yang L, et al (2011). Expression of DNMT1 and DNMT3a are regulated by GLI1 in human pancreatic cancer. PLoS One, 6, e27684. https://doi.org/10.1371/journal.pone.0027684
  10. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  11. Jiang J, Jia Z, Cao D, et al (2012). Polymorphisms of the DNA methyltransferase 1 associated with reduced risks of Helicobacter pylori infection and increased risks of gastric atrophy. PLoS One, 7, e46058. https://doi.org/10.1371/journal.pone.0046058
  12. Kelemen LE, Goodman MT, McGuire V, et al (2010). Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium. Cancer Epidemiol Biomarkers Prev, 19, 1822-30. https://doi.org/10.1158/1055-9965.EPI-09-1317
  13. Kim MS, Kim YR, Yoo NJ, Lee SH (2013). Mutational analysis of DNMT3a gene in acute leukemias and common solid cancers. APMIS, 121, 85-94. https://doi.org/10.1111/j.1600-0463.2012.02940.x
  14. Lehours P, Ruskone-Fourmestraux A, Lavergne A, Cantet F, Megraud F (2003). Which test to use to detect Helicobacter pylori infection in patients with low-grade gastric mucosaassociated lymphoid tissue lymphoma? Am J Gastroenterol, 98, 291-5. https://doi.org/10.1111/j.1572-0241.2003.t01-1-07264.x
  15. Maekita T, Nakazawa K, Mihara M, et al (2006). High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res, 12, 989-95. https://doi.org/10.1158/1078-0432.CCR-05-2096
  16. Malfertheiner P, Megraud F, O'Morain CA, et al(2012). Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut, 61, 646-64. https://doi.org/10.1136/gutjnl-2012-302084
  17. Oh BK, Kim H, Park HJ, et al (2007). DNA methyltransferase expression and DNA methylation in human hepatocellular carcinoma and their clinicopathological correlation. Int J Mol Med, 20, 65-73.
  18. Mavaddat N, Dunning AM, Ponder BA, Easton DF, Pharoah PD (2009). Common genetic variation in candidate genes and susceptibility to subtypes of breast cancer. Cancer Epidemiol Biomarkers Prev, 18, 255-9. https://doi.org/10.1158/1055-9965.EPI-08-0704
  19. Nakajima T, Maekita T, Oda I, et al (2006). Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers. Cancer Epidemiol Biomarkers Prev, 15, 2317-21. https://doi.org/10.1158/1055-9965.EPI-06-0436
  20. Nakajima T, Yamashita S, Maekita T, et al (2009). The presence of a methylation fingerprint of Helicobacter pylori infection in human gastric mucosae. Int J Cancer, 124, 905-10. https://doi.org/10.1002/ijc.24018
  21. Park SY, Yoo EJ, Cho NY, Kim N, Kang GH (2009). Comparison of CpG island hypermethylation and repetitive DNA hypomethylation in premalignant stages of gastric cancer, stratified for Helicobacter pylori infection. J Pathol, 219, 410-6. https://doi.org/10.1002/path.2596
  22. Rahman MM, Qian ZR, Wang EL, et al(2010). DNA methyltransferases 1, 3a, and 3b overexpression and clinical significance in gastroenteropancreatic neuroendocrine tumors. Hum Pathol, 41, 1069-78. https://doi.org/10.1016/j.humpath.2010.01.011
  23. Saeki N, Ono H, Sakamoto H, Yoshida T (2013). Genetic factors related to gastric cancer susceptibility identified using a genome-wide association study. Cancer Sci, 104, 1-8. https://doi.org/10.1111/cas.12042
  24. Tsang DP, Cheng AS (2011). Epigenetic regulation of signaling pathways in cancer: role of the histone methyltransferase EZH2. J Gastroenterol Hepatol, 26, 19-27.
  25. Wang ZK, Liu J, Liu C, et al (2012). Hypermethylation of adenomatous polyposis coli gene promoter is associated with novel Wnt signaling pathway in gastric adenomas. J Gastroenterol Hepatol, 27, 1629-34. https://doi.org/10.1111/j.1440-1746.2012.07219.x
  26. Weisenberger DJ, Velicescu M, Preciado-Lopez MA, et al (2002). Identification and characterization of alternatively spliced variants of DNA methyltransferase 3a in mammalian cells. Gene, 298, 91-9. https://doi.org/10.1016/S0378-1119(02)00976-9
  27. Wu Q, Lu S, Wang L, et al (2012). DNMT3a rs36012910 A>G polymorphism and gastric cancer susceptibility in a Chinese population. Mol Biol Rep, 39, 10949-55. https://doi.org/10.1007/s11033-012-1996-y
  28. Yamada N, Nishida Y, Tsutsumida H, et al (2008). MUC1 expression is regulated by DNA methylation and histone H3 lysine 9 modification in cancer cells. Cancer Res, 68, 2708-16. https://doi.org/10.1158/0008-5472.CAN-07-6844
  29. Yang J, Wei X, Wu Q, et al (2011). Clinical significance of the expression of DNA methyltransferase proteins in gastric cancer. Mol Med Rep, 4, 1139-43.
  30. Yang XX, He XQ, Li FX, et al (2012). Risk-association of DNA methyltransferases polymorphisms with gastric cancer in the southern chinese population. Int J Mol Sci, 13, 8364-78. https://doi.org/10.3390/ijms13078364
  31. Zhao Z, Li C, Song Y, et al (2012). Association of the DNMT3a-448A>G polymorphism with genetic susceptibility to colorectal cancer. Oncol Lett, 3, 450-4.

Cited by

  1. Efficacy and Safety of Docetaxel or Epirubicin, Combined with Cisplatin and Fluorouracil, (DCF and ECF) Regimens as First Line Chemotherapy for Advanced Gastric Cancer: a Retrospective Analysis from Turkey vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6727
  2. Association of DNA Methyltransferases 3A and 3B Polymorphisms, and Plasma Folate Levels with the Risk of Urothelial Carcinoma vol.9, pp.8, 2014, https://doi.org/10.1371/journal.pone.0104968
  3. Common Genetic Variations in the MUC5AC Gene are Not Related to Helicobacter pylori Serologic Status vol.15, pp.24, 2015, https://doi.org/10.7314/APJCP.2014.15.24.10719
  4. and host genetic variants in gastric carcinogenesis vol.12, pp.18, 2016, https://doi.org/10.2217/fon-2016-0233
  5. DNA methyltransferases and gastric cancer: insight into targeted therapy pp.1750-192X, 2018, https://doi.org/10.2217/epi-2018-0096
  6. with gastric cancer in a Chinese population vol.14, pp.17, 2018, https://doi.org/10.2217/fon-2017-0707