TY - JOUR
T1 - Bulky DNA adducts in white blood cells: a pooled analysis of 3,600 subjects
AU - Ricceri, Fulvio
AU - Godschalk, Roger W
AU - Peluso, Marco
AU - Phillips, David H
AU - Agudo, Antonio
AU - Georgiadis, Panagiotis
AU - Loft, Steffen
AU - Tjønneland, Anne
AU - Raaschou-Nielsen, Ole
AU - Palli, Domenico
AU - Perera, Frederica
AU - Vermeulen, Roel
AU - Taioli, Emanuela
AU - Sram, Radim J
AU - Munnia, Armelle
AU - Rosa, Fabio
AU - Allione, Alessandra
AU - Matullo, Giuseppe
AU - Vineis, Paolo
N1 - ©2010 AACR.
PY - 2010/12/1
Y1 - 2010/12/1
N2 - Background: Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect the ability of an individual to metabolically activate carcinogens and to repair DNA damage. Polycyclic aromatic hydrocarbons (PAHs) represent a major class of carcinogens that are capable of forming such adducts. Factors that have been reported to be related to DNA adduct levels include smoking, diet, body mass index (BMI), genetic polymorphisms, the season of collection of biologic material, and air pollutants. Methods: We pooled 11 studies (3,600 subjects) in which bulky DNA adducts were measured in human white blood cells with similar 32P-postlabeling techniques and for which a similar set of variables was available, including individual data on age, gender, ethnicity, batch, smoking habits, BMI, and season of blood collection, and a limited set of gene variants. Results: Lowest DNA adduct levels (P = 0.006) were observed in the spring (median = 0.50 adducts per 108 nucleotides), followed by summer (0.64), autumn (0.70), and winter (0.85). The same pattern emerged in multivariate analysis but only among never smokers (P = 0.02). Adduct levels were significantly lower (P = 0.001) in northern Europe (the Netherlands and Denmark; mean = 0.60, median = 0.40) than in southern Europe (Italy, Spain, France, and Greece; mean = 0.79, median = 0.60). Conclusions: In this large pooled analysis, we have found only weak associations between bulky DNA adducts and exposure variables. Seasonality (with higher adducts levels in winter) and air pollution may partly explain some of the interarea differences (north vs. south Europe), but most inter-area and interindividual variations in adduct levels still remain unexplained. Impact: Our study describes the largest pooled analysis of bulky DNA adducts so far, showing that interindividual variation is still largely unexplained, though seasonality seems to play a role.
AB - Background: Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect the ability of an individual to metabolically activate carcinogens and to repair DNA damage. Polycyclic aromatic hydrocarbons (PAHs) represent a major class of carcinogens that are capable of forming such adducts. Factors that have been reported to be related to DNA adduct levels include smoking, diet, body mass index (BMI), genetic polymorphisms, the season of collection of biologic material, and air pollutants. Methods: We pooled 11 studies (3,600 subjects) in which bulky DNA adducts were measured in human white blood cells with similar 32P-postlabeling techniques and for which a similar set of variables was available, including individual data on age, gender, ethnicity, batch, smoking habits, BMI, and season of blood collection, and a limited set of gene variants. Results: Lowest DNA adduct levels (P = 0.006) were observed in the spring (median = 0.50 adducts per 108 nucleotides), followed by summer (0.64), autumn (0.70), and winter (0.85). The same pattern emerged in multivariate analysis but only among never smokers (P = 0.02). Adduct levels were significantly lower (P = 0.001) in northern Europe (the Netherlands and Denmark; mean = 0.60, median = 0.40) than in southern Europe (Italy, Spain, France, and Greece; mean = 0.79, median = 0.60). Conclusions: In this large pooled analysis, we have found only weak associations between bulky DNA adducts and exposure variables. Seasonality (with higher adducts levels in winter) and air pollution may partly explain some of the interarea differences (north vs. south Europe), but most inter-area and interindividual variations in adduct levels still remain unexplained. Impact: Our study describes the largest pooled analysis of bulky DNA adducts so far, showing that interindividual variation is still largely unexplained, though seasonality seems to play a role.
KW - DNA Adducts
KW - Female
KW - Humans
KW - Leukocytes
KW - Male
KW - Seasons
U2 - 10.1158/1055-9965.EPI-10-0314
DO - 10.1158/1055-9965.EPI-10-0314
M3 - Journal article
C2 - 20921335
SN - 1055-9965
VL - 19
SP - 3174
EP - 3181
JO - Cancer Epidemiology, Biomarkers & Prevention
JF - Cancer Epidemiology, Biomarkers & Prevention
IS - 12
ER -