Bronchial malondialdehyde DNA adducts, tobacco smoking, and lung cancer.
Tobacco smoking is a major risk factor for lung cancer causing, among other effects, oxidative stress and lipid peroxidation. Malondialdehyde (MDA)-DNA adducts can be induced by direct DNA oxidation and by lipid peroxidation. We measured the relationship between bronchial MDA-DNA adducts and tobacco smoking, cancer status, and selected polymorphisms in 43 subjects undergoing a bronchoscopic examination for diagnostic purposes. MDA-DNA adducts were higher in current smokers than in never smokers (frequency ratio (FR) = 1.51, 95% confidence interval (CI) 1.01-2.26). MDA-DNA adducts were also increased in lung cancer cases with respect to controls, but only in smokers (FR = 1.70, 95% CI 1.16-2.51). Subjects with GA and AA cyclin D1 (CCND1) genotypes showed higher levels of MDA-DNA adducts than those with the wild-type genotype (FR = 1.51 (1.04-2.20) and 1.45 (1.02-2.07)). Lung cancer cases with levels of MDA-DNA adducts over the median showed a worse, but not statistically significant, survival, after adjusting for age, gender, and packyears (hazard ratio = 2.48, 95% CI 0.65-9.44). Our findings reinforce the role of smoking in lung carcinogenesis through oxidative stress. Subjects who carry at least one variant allele of the CCND1 gene could accumulate DNA damage for altered cell-cycle control and reduced DNA repair proficiency.
Munnia
Armelle
A
Cancer Risk Factor Branch, CSPO-Scientific Institute of Tuscany Region, Villa Delle Rose, Via Cosimo il Vecchio No. 2, Florence 50139, Italy.
Bonassi
Stefano
S
Verna
Anna
A
Quaglia
Roberto
R
Pelucco
David
D
Ceppi
Marcello
M
Neri
Monica
M
Buratti
Marina
M
Taioli
Emanuela
E
Garte
Seymour
S
Peluso
Marco
M
D000368:Aged; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics; D018736:DNA Adducts; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
D018736:DNA Adducts; D019938:Cyclin D1; D008315:Malondialdehyde