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Smoking-related DNA adducts in anal epithelium
Authors:David H. Phillips   Alan Hewer   John H. Scholefield  Paul Skinner
Affiliation:a Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton SM2 5NG, UK;b Queens Medical Centre, Nottingham University Hospital, Nottingham NG7 2UH, UK;c Sheffield Northern General Hospital NHS Trust, Herries Road, Sheffield S5 7AU, UK
Abstract:Several studies have identified tobacco smoking as a risk factor for anal cancer in both women and men. Samples of anal epithelium from haemorrhoidectomy specimens from current smokers (n=20) and age-matched life-long non-smokers (n=16) were analysed for DNA adducts by the nuclease P1 digestion enhancement procedure of 32P-postlabelling analysis. The study included 14 men and 22 women. Both qualitative and quantitative differences in the adduct profiles were observed between the smokers and non-smokers. The mean adduct level was significantly higher in the smokers than in the non-smokers (1.88±0.71 (S.D.) versus 1.36±0.60 adducts per 108 nucleotides, P=0.02, two-tailed unpaired t-test with Welch’s correction); furthermore, the adduct pattern seen in two-dimensional chromatograms revealed the smoking-related diagonal radioactive zone in 17/20 smokers, but not in any of the non-smokers (P<0.00001, Fisher’s exact test). These results indicate that components of tobacco smoke inflict genotoxic damage in the anal epithelium of smokers and provide a plausible mechanism for a causal association between smoking and anal cancer.
Keywords:DNA adducts   32P-postlabelling   Anal cancer   Tobacco smoking
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