title: Association between cyclin D1 polymorphism with CpG island promoter methylation status of tumor suppressor genes in gastric cancer.
abstract: BACKGROUND
  CpG island hypermethylation of tumor suppressor genes is highly involved in gastric carcinogenesis, and enhanced cell proliferation could accelerate this process. Cyclin D1 regulates cell cycle function and may play a role in methylation-related carcinogenesis.
  
  
  OBJECTIVE
  We investigated the association between Cyclin D1 gene G870A polymorphism and the methylation status of tumor suppressor genes in gastric cancer.
  
  
  METHODS
  Polymorphisms at G870A in the Cyclin D1 gene were genotyped, and methylation status of the p14, p16, DAP-kinase, and CDH1 genes were determined by methylation-specific-polymerase chain reaction in 139 gastric cancer tissues. CIHM high was defined as three or more methylated CpG islands.
  
  
  RESULTS
  Although no association was found between methylation status and different stages and Lauren's subtypes, patients with CIHM of DAP-kinase showed significantly worse survival than those without (p = 0.017). In addition, the number of methylated sites was also associated with survival curves (p = 0.0397). The 870G carrier a significantly lower prevalence of CIHM high compared to the AA genotype in advanced-stage gastric cancer (adjusted OR = 0.32, p = 0.047). A weak correlation between the same genotypes and CIHM of p14 were found in the same subtype (adjusted OR = 0.32, p = 0.052). The mean methylation number was significantly lower in G carriers than in AA genotypes in advanced-stage gastric cancer (p = 0.017).
  
  
  CONCLUSIONS
  Genetic polymorphism of CCND1 is associated with CIHM status in gastric cancer, especially in the advanced stage, but is independent of clinico-pathological features.
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-Cho, Toyoake, Aichi 470-1192, Japan. tomomiccyu@yahoo.co.jp
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshioka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okubo
authors.forename: Joh
authors.initials: J
authors.lastname: Yonemura
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Maeda
authors.forename: Naoko
authors.initials: N
authors.lastname: Maruyama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kamano
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.forename: Masami
authors.initials: M
authors.lastname: Iwata
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
mesh_terms: D000368:Aged; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D019940:Genes, bcl-1 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
references.citation: Cancer Res. 2001 May 1;61(9):3573-7
references.pmid: 11325821
references.citation: Cancer Res. 1999 Nov 1;59(21):5438-42
references.pmid: 10554013
references.citation: Carcinogenesis. 2002 Feb;23(2):257-64
references.pmid: 11872630
references.citation: Cancer Res. 2001 Apr 1;61(7):2847-51
references.pmid: 11306456
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6
references.pmid: 8790415
references.citation: Acta Pathol Microbiol Scand. 1965;64:31-49
references.pmid: 14320675
references.citation: Oncogene. 1998 Apr 2;16(13):1701-12
references.pmid: 9582018
references.citation: Cancer Res. 2002 Jun 1;62(11):3200-6
references.pmid: 12036934
references.citation: Blood. 1999 Jun 15;93(12):4347-53
references.pmid: 10361133
references.citation: Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):989-95
references.pmid: 16467114
references.citation: Oncogene. 1995 Sep 7;11(5):1005-11
references.pmid: 7675441
references.citation: Int J Oncol. 2005 Jun;26(6):1493-500
references.pmid: 15870861
references.citation: Neoplasma. 2007;54(3):235-9
references.pmid: 17447856
references.citation: Mol Cell Biol. 1995 Jul;15(7):3463-9
references.pmid: 7791752
references.citation: Cancer Res. 2000 Jan 15;60(2):249-52
references.pmid: 10667569
references.citation: Aliment Pharmacol Ther. 2002 Apr;16 Suppl 2:145-57
references.pmid: 11966535
references.citation: Clin Chem Lab Med. 2008;46(12):1696-701
references.pmid: 19055446
references.citation: Int J Radiat Oncol Biol Phys. 2001 Apr 1;49(5):1305-10
references.pmid: 11286838
references.citation: Cancer Res. 2000 Jan 1;60(1):129-33
references.pmid: 10646864
references.citation: Cancer Sci. 2003 Apr;94(4):360-4
references.pmid: 12824905
references.citation: Eur J Gastroenterol Hepatol. 2009 Jun;21(6):613-9
references.pmid: 19307977
references.citation: Exp Cell Res. 2001 Mar 10;264(1):185-92
references.pmid: 11237533
references.citation: Oncogene. 1993 Dec;8(12):3447-57
references.pmid: 8247550
references.citation: Oncogene. 2001 Oct 25;20(48):7104-9
references.pmid: 11704835
references.citation: Oncogene. 2000 Jun 15;19(26):2978-85
references.pmid: 10871849
references.citation: Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7634-8
references.pmid: 8755527
references.citation: Carcinogenesis. 2001 Nov;22(11):1801-7
references.pmid: 11698342
references.citation: Clin Cancer Res. 2009 Jul 1;15(13):4431-8
references.pmid: 19549773
references.citation: Infect Immun. 2001 Jun;69(6):3965-71
references.pmid: 11349065
references.citation: J Biol Chem. 2000 May 26;275(21):16064-72
references.pmid: 10747974
references.citation: Am J Pathol. 2001 Nov;159(5):1917-24
references.pmid: 11696452
references.citation: Cancer Invest. 2009 May;27(4):459-65
references.pmid: 19160099
references.citation: Genes Dev. 1993 Aug;7(8):1559-71
references.pmid: 8339933
references.citation: Cancer Res. 2002 Apr 15;62(8):2378-84
references.pmid: 11956100
references.citation: Mol Carcinog. 2007 Sep;46(9):807-17
references.pmid: 17393422
references.citation: Curr Top Microbiol Immunol. 2000;249:101-18
references.pmid: 10802941
references.citation: Int J Cancer. 2003 Jun 10;105(2):281-4
references.pmid: 12673692
references.citation: Int J Gynecol Cancer. 1999 Jul;9(4):342-347
references.pmid: 11240791
references.citation: World J Gastroenterol. 2004 Feb 15;10(4):491-6
references.pmid: 14966904
references.citation: Int J Cancer. 2000 Oct 1;88(1):77-81
references.pmid: 10964085
references.citation: Hum Pathol. 1999 Sep;30(9):1087-92
references.pmid: 10492044
references.citation: Cancer Lett. 1997 Feb 26;113(1-2):123-30
references.pmid: 9065811
references.citation: Genes Chromosomes Cancer. 2002 Jul;34(3):276-84
references.pmid: 12007188
references.citation: Am J Pathol. 2003 Oct;163(4):1551-6
references.pmid: 14507661
references.citation: Hum Pathol. 2008 Nov;39(11):1637-46
references.pmid: 18657295
references.citation: Science. 1996 Dec 6;274(5293):1672-7
references.pmid: 8939849
references.citation: Biochem Biophys Res Commun. 2008 May 23;370(1):118-22
references.pmid: 18355450
references.citation: Gut. 2003 Apr;52(4):502-6
references.pmid: 12631658