Barrow TM, et al. – This research aspired to determine the epigenetic changes related to smoking behaviours. Exploratory evidence was yielded for hypermethylation of the key tumour suppressor gene APC being implicated in smoking–associated colorectal carcinogenesis. In order to establish the validity of these observations in independent cohorts, advanced studies were warranted.

Methods

• An epigenome-wide analysis was pursued of DNA methylation in colorectal tumours from 36 never smokers, 47 former smokers and 13 active smokers, and adjacent mucosa from 49 never smokers, 64 former smokers and 18 active smokers.

Results

• 15 CpG sites were detected within the APC 1A promoter.
• These were prominently hypermethylated.
• 14 CpG loci within the NFATC1 gene body were significantly hypomethylated (pLIS<1x10-5) in tumours of active smokers.
• The APC 1A promoter was hypermethylated in 7 of 36 tumours from never smokers (19%), 12 of 47 tumours from former smokers (26%), and 8 of 13 tumours from active smokers (62%).
• A positive link was noted between promoter hypermethylation with duration of smoking (Spearman rank correlation, ρ=0.26, p=0.03).
• It was confined to tumours, with hypermethylation never being observed in adjacent mucosa.
• Additional assessment of adjacent mucosa disclosed marked hypomethylation of four loci related to the TNXB gene in tissue from active smokers.