title: Gender differences in autoantibodies to oxidative DNA base damage in cigarette smokers.
abstract: 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 alpha-carotene and beta-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 alpha-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 <or=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 <or=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 <or=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.
authors.affiliation: Department of Environmental Health Sciences, Joseph L. Mailman School of Public Health, Columbia University, New York, New York 10032, USA. lam14@columbia.edu
authors.forename: L A
authors.initials: LA
authors.lastname: Mooney
authors.forename: F P
authors.initials: FP
authors.lastname: Perera
authors.forename: A M
authors.initials: AM
authors.lastname: Van Bennekum
authors.forename: W S
authors.initials: WS
authors.lastname: Blaner
authors.forename: J
authors.initials: J
authors.lastname: Karkoszka
authors.forename: L
authors.initials: L
authors.lastname: Covey
authors.forename: Y
authors.initials: Y
authors.lastname: Hsu
authors.forename: T B
authors.initials: TB
authors.lastname: Cooper
authors.forename: K
authors.initials: K
authors.lastname: Frenkel
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000032:analysis / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D004249:DNA Damage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D013936:Thymidine / Q000031:analogs & derivatives / Q000032:analysis / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D001323:Autoantibodies; D015415:Biomarkers; C018080:5-hydroxymethyl-2'-deoxyuridine; D013936:Thymidine