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Gender Differences in Autoantibodies to Oxidative DNA Base Damage in Cigarette Smokers¹

Department of Environmental Health Sciences, Joseph L. Mailman School of Public Health [L. A. M., F. P. P., Y. H.], Institute of Human Nutrition [A. M. V., W. S. B.], and Department of Psychiatry, College of Physicians and Surgeons [L. C.], Columbia University, New York, New York 10032; School of Medicine, New York University, New York, New York 10016 [J. K., K. F.]; and New York State Psychiatric Institute, New York, New York 10032 [L. C., T. C.]

Oxidative DNA damage and antibodies to that damage have been implicated in lung, breast, and colorectal cancer. In this observational validation study, the relationship between anti-5-hydroxymethyl-2'-deoxyuridine (HMdU) autoantibody (aAb) and plasma micronutrients was assessed in 140 heavy smokers by ELISA. Anti-HMdU aAbs were 50% higher in women after adjustment for cigarettes/day (CPD; P = 0.002), although men smoked more and had higher plasma cotinine levels. The women reported taking more vitamin C (P < 0.005) and had higher plasma levels of -carotene and ß-carotene (P < 0.001) and cryptoxanthin (P < 0.01) than men. Neither CPD nor cotinine was associated with aAb titers. Anti-HMdU aAbs were associated inversely with -tocopherol (P = 0.10), retinol (P = 0.06), and age (P = 0.04) in women but not in men. In contrast to the men, women 50 years of age had significantly higher aAbs than those >50 years of age (P = 0.05). Given the same duration of exposure, women had higher anti-HMdU aAbs and also reached peak levels at a lower cumulative smoking exposure (30 years) compared with male smokers (40 years). Subjects smoked an average of 28.9 ± 0.81 CPD and initiated smoking at 17.2 ± 0.33 (SE) years of age. Therefore, smokers who reported smoking for 30 years were typically <50 years old. Women 50 years in the younger age group that smoked 21–30 years had significantly higher levels of aAbs than did men of the same age and smoking history (P = 0.012).

Gender difference in aAbs was also evident in 29 persons who gave serial samples before and after quitting smoking (P < 0.028). In women, aAbs remained elevated for 14 months after smoking cessation but decreased significantly by 20.5 months (P < 0.032) by paired t tests. In men, aAbs increased with time since quitting smoking but not significantly.

The finding of significantly elevated aAbs to oxidized DNA in females 50 compared with male smokers of the same age and exposure suggests a possible interaction with hormones (e.g., estrogens) and may explain a heightened risk of smoking-induced lung cancer in women compared with men.

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