MYOD-1 in normal colonic mucosa – role as a putative biomarker?

BMC Research Notes

Mike Bradburn³  John C Mathers¹  Daniel Commane¹  M Nabil Quraishi²  Ramesh P Arasaradnam⁴ 

[1] Human Nutrition Research Institute, Newcastle University, Newcastle, UK;Department of Gastroenterology, University Hospital Coventry & Warwickshire, Coventry, UK;Department of Colorectal Surgery, Wansbeck General Hospital, Wansbeck, Northumberland, UK;Clinical Sciences Research Institute, Warwick Medical School, Clifford Bridge Road, Coventry, CV2 2DX, UK

关键词: Promoter methylation;    Age;    Colorectal cancer;    MYOD-1;   

Others  :  1166416
DOI  :  10.1186/1756-0500-5-240

 received in 2011-12-14, accepted in 2012-05-16,  发布年份 2012

【 摘 要 】

Background

DNA methylation of promoter-associated CpG islands of certain genes may play a role in the development of colorectal cancer. The MYOD-1 gene which is a muscle differentiation gene has been showed to be significantly methylated in colorectal cancer which, is an age related event. However the role of this gene in the colonic mucosa is not understood and whether methylation occurs in subjects without colon cancer. In this study, we have determined the frequency of methylation of the MYOD-1 gene in normal colonic mucosa and investigated to see if this is associated with established colorectal cancer risk factors primarily ageing.

Results

We analysed colonic mucosal biopsies in 218 normal individuals and demonstrated that in most individuals promoter hypermethylation was not quantified for MYOD-1. However, promoter hypermethylation increased significantly with age (p < 0.001 using regression analysis) and this was gender independent. We also showed that gene promoter methylation increased positively with an increase in waist to hip (WHR) ratio – the latter is also a known risk factor for colon cancer development.

Conclusions

Our study suggests that promoter gene hypermethylation of the MYOD-1 gene increases significantly with age in normal individuals and thus may offer potential as a putative biomarker for colorectal cancer.

【 授权许可】

   
2012 Arasaradnam et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Kinzler KW, Vogelstein B: Lessons from hereditary colorectal cancer. Cell 1996, 87(2):159-170.
• [2]Jones PA, Baylin SB: The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002, 3(6):415-428.
• [3]Jones PA: DNA Methylation errors and cancer. Cancer Res 1996, 56(11):2463-2467.
• [4]Agrawal A, Murphy RF, Agrawal DK: DNA methylation in breast and colorectal cancers. Mod Pathol 2007, 20(7):711-721.
• [5]Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB: Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genetics 1994, 7(4):536-540.
• [6]Arasaradnam RP, Commane DM, Bradburn D, Mathers JC: A review of dietary factors and its influence on DNA methylation in colorectal carcinogenesis. Epigenetics 2008, 3(4):193-198.
• [7]Wallner M, Herbst A, Behrens A, Crispin A, Stieber P, Göke B, et al.: Methylation of serum DNA is an independent prognostic marker in colorectal cancer. Clin Cancer Res 2006, 12:7347-7352.
• [8]Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP: Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res 1998, 58(23):5489-5494.
• [9]Hiranuma C, Kawakami K, Oyama K, Ota N, Omura K, Watanabe G: Hypermethylation of the MYOD1 gene is a novel prognostic factor in patients with colorectal cancer. Int J Mol Med 2004, 13(3):413-417.
• [10]Megeney LA, Kablar B, Garrett K, Anderson JE, Rudnicki MA: MyoD is required for myogenic stem cell function in adult skeletal muscle. Genes Dev 1996, 10:1173-1183.
• [11]Davis RL, Cheng PF, Lassar AB, Weintraub H: The MyoD DNA binding domain contains recognition code for muscle-specific gene activation. Cell 1990, 60(5):733-746.
• [12]Cancer Research UK: Cancer Statistics Registrations: Registrations of Cancer Diagnosed in 2007. Office for National Statistics, England; Available at: http://www.ons.gov.uk/ons/rel/vsob1/cancer-statistics-registrations--england--series-mb1-/no--39--2008/cancer-statistics--registrations-series-mb1.pdf webcite (Accessed: 2nd July 2011)
• [13]Ye C, Shrubsole MJ, Cai Q, Ness R, Grady WM, Smalley W: Promoter methylation status of the MGMT, hMLH1, and CDKN2A/p16 genes in non-neoplastic mucosa of patients with and without colorectal adenomas. Oncol Rep 2006, 16(2):429-435.
• [14]Kawakami K, Ruszkiewicz A, Bennett G, Moore J, Grieu F, Watanabe G: DNA hypermethylation in the normal colonic mucosa of patients with colorectal cancer. Br J Cancer 2006, 94(4):593-598.
• [15]Issa JP, Ahuja N, Toyota M, Bronner MP, Brentnall TA: Accelerated Age-related CpG Island Methylation in Ulcerative Colitis. Cancer Res 2001, 61(9):3573-3577.
• [16]Xu XL, Yu J, Zhang HY, Sun MH, Gu J, Du X, Shi DR: Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis. World J Gastroenterology 2004, 10(23):3441-3454.
• [17]Chen X, Liu H, Li L, Si J, Wang J: Expression of the MYOD Gene Family on Small Intestine development of ducks. China Poultry, China; 2010:8.
• [18]Friedenreich C, Norat T, Steindorf K, Boutron-Ruault MC, Pischon T, Mazuir M, et al.: Physical activity and risk of colon and rectal cancers: the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 2006, 15(12):2398-2407.
• [19]Xiong Z, Laird P: COBRA: a sensitive and quantitative DNA methylation assay. Nucl. Acids Res. 1997, 25(12):2532-2534.