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Antibodies against 5-Hydroxymethyl-2'-deoxyuridine Are Associated with Lifestyle Factors and GSTM1 Genotype

A Report from the Malmö Diet and Cancer Cohort¹

Departments of Medicine [P. W., E. W., G. B.] and Community Medicine [B. G., L. J.], Lund University, Malmö University Hospital, SE-205 02 Malmö, Sweden; Nelson Institute of Environmental Medicine, New York University School of Medicine, New York, New York [K. F., J. K.]; and Active Biotech Research AB, Lund, Sweden [J. S.]

Plasma autoantibodies (aAbs) against the oxidized DNA base derivative 5-hydroxymethyl-2'-deoxyuridine (5-HMdU) are potential biomarkers of cancer risk and oxidative stress. We examined their association with a number of cancer risk factors: smoking, alcohol habits, body fatness, and absence of the glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) in a sample from the population-based Malmö Diet and Cancer cohort (Sweden).

This was a cross-sectional study of 264 men and 280 women, 46–67 years of age. Anti-5-HMdU aAb concentration was determined by an ELISA. Data on tobacco exposure were collected through a questionnaire. Alcohol consumption was estimated by a modified diet history method. Body fatness was assessed by a bioimpedance method. The absence or presence of genes coding for GSTM1 and GSTT1 was determined in granulocyte DNA by a multiplex PCR technique.

aAb titers were significantly greater in those with high alcohol consumption. Current smokers lacking GSTM1, particularly men, had greater aAb titers compared with nonsmokers or persons expressing GSTM1. Body fatness was inversely associated with antibody titers in men. GSTT1 genotype was not associated with aAb titers. Overall, women had higher aAb titers than men. Adjustment for potential confounders (history of chronic diseases, anti-inflammatory medication, and season of blood sampling) did not change the results.

Our study shows that a high alcohol consumption, smoking in combination with lack of GSTM1, and low body fatness (in men) is associated with high titers of anti-5-HMdU aAbs in this population.