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Smoking is Associated with Changes in DNA Methylation of the MGMT and SEPT9 Genes in Colorectal Cancer – the ColoCare Study

Lookup NU author(s): Dr Timothy Barrow


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Normal 0 false false false DE JA X-NONE Smoking tobacco is a known risk factor for the development of colorectal cancer, and for mortality associated with the disease. While smoking has been reported to be associated with changes in DNA methylation in blood and in bladder and lung tissue, there has been little work to date exploring how epigenetic factors may be implicated in the increased risk of developing colorectal cancer. We investigated DNA methylation within 14 genes (AHRR, APC, CDKN2A/p16, DNMT3B, F2RL3, IGF2, MGMT, MLH1, MSH2, MTHFR, RARB, RASSF1, RUNX3, and SEPT9) in colorectal tumours and mucosa adjacent to tumours (AM) collected from 26 never-smokers and 36 ever-smokers. We identified 10 CpG sites that were significantly differentially methylated in tumours by smoking status (p < 0.05 following FDR), and 34 sites that were significantly different in AM by smoking status. Significant differences were seen in both tumours and AM within MGMT (2 in tumours, 6 in AM) and SEPT9 (2 in tumours, 3 in AM). Methylation at cg07828472 (MGMT) in tumours and at cg06848185 (SEPT9) in AM were significantly associated with pack-years of smoking (Spearman’s rank correlation coefficient, p < 0.05). Within the CpG island containing the SEPT9 cg06848185 locus (chr17:75368689-75370506), we observed considerable statistically significant differences (Db > 0.16; p < 0.0001) in median methylation levels at all 10 loci between tumours and AM. Our results identify MGMT and SEPT9 as being differentially methylated among smokers at regions displaying significant differences between histologically-normal mucosa and tumours, thereby possibly implicating these genes in the increased risk of colorectal cancer associated with smoking.

Publication metadata

Author(s): Barrow TM, Toth R, Gigic B, Habermann N, Scherer D, Schrotz-King P, Böhm J, Tosic S, Abbenhardt C, Schneider M, Ulrich A, Schirmacher P, Herpel E, Michels KB, Ulrich CM

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Epigenomics of Common Diseases

Year of Conference: 2014