DNA adducts and lung cancer risk: a prospective study.
Objectives were to investigate prospectively the ability of DNA adducts to predict cancer and to study the determinants of adducts, especially air pollutants. DNA adducts were measured in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) investigation. Cases included newly diagnosed lung cancer (n = 115), upper respiratory cancers (pharynx and larynx; n = 82), bladder cancer (n = 124), leukemia (n = 166), and chronic obstructive pulmonary disease or emphysema deaths (n = 77) accrued after a median follow-up of 7 years among the EPIC former smokers and never-smokers. Three controls per case were matched for questionnaire analyses and two controls per case for laboratory analyses. Matching criteria were gender, age, smoking status, country of recruitment, and follow-up time. Individual exposure to air pollution was assessed using concentration data from monitoring stations in routine air quality monitoring networks. Leukocyte DNA adducts were analyzed blindly using 32P postlabeling technique. Adducts were associated with the subsequent risk of lung cancer, with an odds ratio (OR) of 1.86 [95% confidence interval (95% CI), 0.88-3.93] when comparing detectable versus nondetectable adducts. The association with lung cancer was stronger in never-smokers (OR, 4.04; 95% CI, 1.06-15.42) and among the younger age groups. After exclusion of the cancers occurring in the first 36 months of follow-up, the OR was 4.16 (95% CI, 1.24-13.88). A positive association was found between DNA adducts and ozone (O3) concentration. Our prospective study suggests that leukocyte DNA adducts may predict lung cancer risk of never-smokers. Besides, the association of DNA adduct levels with O3 indicates a possible role for photochemical smog in determining DNA damage.
Peluso
Marco
M
Cancer Risk Factor Branch, CSPO-Scientific Institute of Tuscany Region, Florence, Italy. m.peluso@cspo.it
Munnia
Armelle
A
Hoek
Gerard
G
Krzyzanowski
Michal
M
Veglia
Fabrizio
F
Airoldi
Luisa
L
Autrup
Herman
H
Dunning
Alison
A
Garte
Seymour
S
Hainaut
Pierre
P
Malaveille
Christian
C
Gormally
Emmanuelle
E
Matullo
Giuseppe
G
Overvad
Kim
K
Raaschou-Nielsen
Ole
O
Clavel-Chapelon
Francoise
F
Linseisen
Jacob
J
Boeing
Heiner
H
Trichopoulou
Antonia
A
Trichopoulos
Dimitrios
D
Kaladidi
Anna
A
Palli
Domenico
D
Krogh
Vittorio
V
Tumino
Rosario
R
Panico
Salvatore
S
Bueno-De-Mesquita
H Bas
HB
Peeters
Petra H
PH
Kumle
Merethe
M
Gonzalez
Carlos A
CA
Martinez
Carmen
C
Dorronsoro
Miren
M
Barricarte
Aurelio
A
Navarro
Carmen
C
Quiros
J Ramón
JR
Berglund
Goran
G
Janzon
Lars
L
Jarvholm
Bengt
B
Day
Nicholas E
NE
Key
Tim J
TJ
Saracci
Rodolfo
R
Kaaks
Rudolf
R
Riboli
Elio
E
Vineis
Paolo
P
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018736:DNA Adducts / Q000097:blood*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors
D018736:DNA Adducts