title: MTHFR C677T polymorphisms are associated with aberrant methylation of the IGF-2 gene in transitional cell carcinoma of the bladder.
abstract: The purpose of this study was to determine the relationship between methylation status of the insulin-like growth factor 2 (IGF-2) gene and methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms in bladder transitional cell carcinoma tissues in a Chinese population. The polymorphisms of the folate metabolism enzyme gene MTHFR were studied by restrictive fragment length polymorphism (RFLP). PCR-based methods of DNA methylation analysis were used to detect the CpG island methylation status of the IGF-2 gene. The association between the methylation status of the IGF-2 gene and clinical characteristics, as well as MTHFR C677T polymorphisms, was analyzed. Aberrant hypomethylation of the IGF-2 gene was found in 68.3% bladder cancer tissues and 12.4% normal bladder tissues, respectively, while hypomethylation was not detected in almost all normal bladder tissues. The hypomethylation rate of the IGF-2 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables the variant allele of MTHFR C677T was found to be associated with hypomethylation of the IGF-2 gene. Compared with wildtype CC, the odds ratio was 4.33 (95% CI=1.06-10.59) for CT and 4.95 (95% CI=1.18-12.74) for TT. MTHFR 677 CC and CT genotypes might be one of the reasons that cause abnormal hypomethylation of the IGF-2 gene, and the aberrant CpG island hypomethylation of the IGF-2 gene may contribute to the genesis and progression of bladder transitional cell carcinoma.
authors.affiliation: Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Cheng
authors.forename: Zhonglei
authors.initials: Z
authors.lastname: Deng
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jiantang
authors.initials: J
authors.lastname: Su
keywords: bladder transitional cell carcinoma; epidemiology; folate; insulin-like growth factor 2 (IGF-2); methylation; methylenetetrahydrofolate reductase
references.citation: Cell. 1997 Feb 7;88(3):333-46
references.pmid: 9039260
references.citation: Mod Pathol. 2007 Jul;20(7):802-10
references.pmid: 17483816
references.citation: Cancer Lett. 2006 Feb 20;233(1):124-30
references.pmid: 16473673
references.citation: J Dent Res. 2011 Jan;90(1):65-70
references.pmid: 20940365
references.citation: Oncogene. 2004 Nov 18;23(54):8841-6
references.pmid: 15480421
references.citation: Curr Issues Mol Biol. 2008;10(1-2):25-36
references.pmid: 18525104
references.citation: AJR Am J Roentgenol. 2009 Jun;192(6):1481-7
references.pmid: 19457808
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Apr;14(4):938-43
references.pmid: 15824167
references.citation: PLoS One. 2010 Aug 23;5(8):e12334
references.pmid: 20808801
references.citation: Mol Genet Metab. 1998 Jul;64(3):169-72
references.pmid: 9719624
references.citation: Int J Oncol. 2011 Sep;39(3):727-33
references.pmid: 21617853
references.citation: J Thyroid Res. 2011;2011:895470
references.pmid: 21765995
references.citation: Nutr Res. 2007 Jan;27(1):1365-1317
references.pmid: 18167510
references.citation: Diagn Pathol. 2006 Nov 08;1:41
references.pmid: 17092354
references.citation: Cancer Res. 2011 Sep 1;71(17):5859-70
references.pmid: 21724586
references.citation: Cancer Res. 1997 Mar 15;57(6):1098-102
references.pmid: 9067278
references.citation: Mol Cell Biochem. 2007 Jan;294(1-2):181-7
references.pmid: 16855792
references.citation: Carcinogenesis. 2007 Mar;28(3):560-71
references.pmid: 17012225
references.citation: Cancer Treat Rev. 2003 Dec;29(6):489-99
references.pmid: 14585259
references.citation: Cell. 1988 Apr 22;53(2):173-4
references.pmid: 3282673
references.citation: Mol Biol Rep. 2006 Dec;33(4):253-6
references.pmid: 17077989
references.citation: Semin Cancer Biol. 2004 Dec;14(6):427-32
references.pmid: 15489135
references.citation: Ann N Y Acad Sci. 2007 Apr;1100:60-74
references.pmid: 17460165
references.citation: Toxicol Mech Methods. 2011 May;21(4):275-88
references.pmid: 21495866
references.citation: Clin Cancer Res. 2006 Feb 15;12(4):1208-14
references.pmid: 16489075
references.citation: Anticancer Res. 2004 Mar-Apr;24(2B):649-54
references.pmid: 15161007
references.citation: Nucleic Acids Res. 1994 Feb 25;22(4):695-6
references.pmid: 8127720
references.citation: Science. 2003 Mar 14;299(5613):1753-5
references.pmid: 12637750
references.citation: Gastroenterol Hepatol. 2008 Jan;31(1):37-45
references.pmid: 18218279
references.citation: Cell. 2007 Feb 23;128(4):683-92
references.pmid: 17320506
references.citation: J Nutr. 2011 Jun;141(6):1165-71
references.pmid: 21525250
references.citation: Dis Esophagus. 2005;18(3):177-84
references.pmid: 16045580
references.citation: Carcinogenesis. 2005 Jul;26(7):1285-90
references.pmid: 15790587
references.citation: PLoS One. 2008 Mar 26;3(3):e1849
references.pmid: 18365005
references.citation: Genetics. 2008 Jan;178(1):215-34
references.pmid: 18202369
references.citation: Cancer Res. 2007 Nov 15;67(22):10753-8
references.pmid: 18006818