DOI QR코드

DOI QR Code

Mll3 Genetic Variants Affect Risk of Gastric Cancer in the Chinese Han Population

  • Li, Bing (Department of Surgical Oncology, General Hospital of the People's Liberation Army) ;
  • Liu, Hong-Yi (Department of Surgical Oncology, General Hospital of the People's Liberation Army) ;
  • Guo, Shao-Hua (Department of Surgical Oncology, General Hospital of the People's Liberation Army) ;
  • Sun, Peng (Department of Surgical Oncology, General Hospital of the People's Liberation Army) ;
  • Gong, Fang-Ming (Department of Surgical Oncology, General Hospital of the People's Liberation Army) ;
  • Jia, Bao-Qing (Department of Surgical Oncology, General Hospital of the People's Liberation Army)
  • Published : 2013.07.30

Abstract

It is reported that the expression level of MLL3 in gastric cancer tissue highly correlates with tumor progression. However, whether MLL3 genetic variants are associated with the risk of gastric cancer remains unclear. In this study, we conducted a genotyping analysis for MLL3 in 314 cases of gastric cancer and 322 controls from the Chinese Han population. 4 SNPs (rs6943984, rs4725443, rs3800836, rs6464211) were selected for the present analysis. We found 2 SNPs (rs6943984, rs4725443) of MLL3 gene were significantly associated with the risk of gastric cancer : the rs6943984 with the minor allele A and rs4725443 with the minor allele C revealed strong associations with increased gastric cancer risk [P < 0.001, OR=1.97, 95% CI=1.48~2.64 and P <0.001, OR=2.23, 95% CI=1.54~3.24]. Haplotype analysis of the four SNPs showed that haplotype A-T-A-C, G-T-G-C, and G-C-A-C increased the risk of gastric cancer (P <0.001, P=0.18, and P<0.001, respectively), while haplotype G-T-A-C significantly reduced the risk of gastric cancer (P <0.001). We concluded that MLL3 variants are significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of MLL3 gene variants in carcinogenesis of gastric cancer of the Chinese Han population.

Keywords

MLL3;gastric cancer;genetic variants;Chinese Han

References

  1. Balakrishnan A, Bleeker FE, Lamba S, et al (2007). Novel somatic and germline mutations in cancer candidate genes in glioblastoma, melanoma, and pancreatic carcinoma. Cancer Res, 67, 3545-50. https://doi.org/10.1158/0008-5472.CAN-07-0065
  2. Dohner K, Brown J, Hehmann U, et al (1998). Molecular cytogenetic characterization of a critical region in bands 7q35-q36 commonly deleted in malignant myeloid disorders. Blood, 92, 4031-35.
  3. Duell EJ, Sala N, Travier N, et al (2012). Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Carcinogenesis, 33, 361-7. https://doi.org/10.1093/carcin/bgr285
  4. Hou R, Cao B, Chen Z, et al (2010). Association of cytotoxic T lymphocyte-associated antigen-4 gene haplotype with the susceptibility to gastric cancer. Mol Biol Rep, 37, 515-20. https://doi.org/10.1007/s11033-009-9705-1
  5. Kim R, Emi M, Tanabe K (2007). Cancer immunoediting from immune surveillance to immune escape. Immunology, 121, 1-14. https://doi.org/10.1111/j.1365-2567.2007.02587.x
  6. Lee J, Kim DH, Lee S, et al (2009). A tumor suppressive coactivator complex of p53 containing ASC-2 and histone H3-lysine-4 methyltransferase MLL3 or its paralogue MLL4. Proc Natl Acad Sci U S A, 106, 8513-8. https://doi.org/10.1073/pnas.0902873106
  7. Li Z, Zhang Z, He Z, et al (2009). A partition-ligationcombination- subdivision EM algorithm for haplotype inference with multiallelic markers, update of the SHEsis (http, //analysis.bio-x.cn). Cell Res, 19, 519-23. https://doi.org/10.1038/cr.2009.33
  8. Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108. https://doi.org/10.3322/canjclin.55.2.74
  9. Ruault M, Brun ME, Ventura M, Roizes G, De SA (2002). MLL3, a new human member of the TRX/MLL gene family, maps to 7q36, a chromosome region frequently deleted in myeloid leukaemia. Gene, 284, 73-81. https://doi.org/10.1016/S0378-1119(02)00392-X
  10. Saha V, Chaplin T, Gregorini A, Ayton P, Young BD (1995). The leukemiaassociated-protein (LAP) domain, a cysteinerich motif, is present in a wide range of proteins, including MLL, AF10, and MLLT6 proteins. Proc Natl Acad Sci U S A, 92, 9737-41. https://doi.org/10.1073/pnas.92.21.9737
  11. Shin CM, Kim N, Lee HS, et al (2011). Intrafamilial aggregation of gastric cancer, a comprehensive approach including environmental factors, Helicobacter pylori virulence, and genetic susceptibility. Eur J Gastroenterol Hepatol, 23, 411-7. https://doi.org/10.1097/MEG.0b013e328343b7f5
  12. Siegel R, Ward E, Brawley O, Jemal A (2011). Cancer statistics, 2011, the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin, 61, 212-36. https://doi.org/10.3322/caac.20121
  13. Watanabe Y, Castoro RJ, Kim HS, et al (2011). Frequent alteration of MLL3 frameshift mutations in microsatellite deficient colorectal cancer. PLoS One, 6, e23320. https://doi.org/10.1371/journal.pone.0023320
  14. Xie X, Ma YT, Fu ZY, et al (2009). Haplotype analysis of the CYP8A1 gene associated with myocardial infarction. Clin Appl Thromb Hemost, 15, 574-80. https://doi.org/10.1177/1076029608329581
  15. Zhang Y, Sun LP, Xing CZ, et al (2012). Interaction between GSTP1 Val allele and H. pylori infection, smoking and alcohol consumption and risk of gastric cancer among the Chinese population. PLoS One, 7, e47178. https://doi.org/10.1371/journal.pone.0047178

Cited by

  1. Downregulation of MLL3 in esophageal squamous cell carcinoma is required for the growth and metastasis of cancer cells vol.36, pp.2, 2015, https://doi.org/10.1007/s13277-014-2616-3
  2. Genetic variation and gastric cancer risk: a field synopsis and meta-analysis vol.64, pp.8, 2015, https://doi.org/10.1136/gutjnl-2015-309168
  3. genetic polymorphisms, smoking, and alcohol drinking in laryngeal cancer: a case-control study vol.5, pp.3, 2016, https://doi.org/10.1002/cam4.589
  4. Genetic variants in the histone methylation and acetylation pathway and their risks in eight types of cancers vol.19, pp.2, 2018, https://doi.org/10.1111/1751-2980.12574