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Medical Research Council Toxicology Unit, University of Leicester, Leicester LE1 9HN, United Kingdom [C. L., E. J. D, R. S., E. G., D. E. G. S.]; Norfolk and Norwich Health Care Trust, NR4 7U4, United Kingdom [M. A. W.]; Strangeways Research Laboratory, European Prospective Investigation on Cancer (EPIC), University of Cambridge, Cambridge, CB1 4RN, United Kingdom [A. W., N. E. D.]; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232 [L. J. M]; Imperial Cancer Research Fund Colorectal Cancer Unit, St. Mark’s Hospital, Middlesex, HA1 3UJ United Kingdom [W. A.]; and Medical Research Council Dunn Human Nutrition Centre, Cambridge, CB2 2X4 United Kingdom [S. A. B]
Colorectal biopsies from normal mucosa of participants in the United Kingdom Flexible Sigmoidoscopy Trial and European Prospective Investigation on Cancer (EPIC; n = 162) were analyzed for the presence of malondialdehyde-deoxyguanosine (M1-dG), a DNA adduct derived from lipid peroxidation. The aim was to investigate whether dietary factors can modulate M1-dG levels and whether M1-dG in normal mucosa is a risk factor for colorectal adenomas. Samples were analyzed using a sensitive immunoslot blot assay. This study has shown for the first time that M1-dG is present in human colorectal tissue. M1-dG levels ranged from undetectable (n = 13) to 12.23 per 107 total bases. Mean levels were 4.3 ± 3 and 4.6 ± 2.9 per 107 total bases in men and women, respectively. In men, there were positive associations of adduct levels with height and age, and inverse associations with body mass index. Legumes, fruit, salad, and whole meal bread were inversely associated with M1-dG adducts, whereas consumption of offal, white meat, beer, and alcohol were positively associated with elevated levels. In women, there was an inverse association of the adduct with the ratio of polyunsaturated:saturated fatty acids (P = 0.019) and a weak positive correlation with saturated fat (P < 0.061). When levels of adducts were compared in individuals with and without adenomas, there was a trend for higher levels in individuals presenting with adenomas especially in the highest category of M1-dG adducts (P < 0.005).
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