Bulky DNA adducts in white blood cells: a pooled analysis of 3,600 subjects

Fulvio Ricceri; Roger W Godschalk; Marco Peluso; David H Phillips; Antonio Agudo; Panagiotis Georgiadis; Steffen Loft; Anne Tjønneland; Ole Raaschou-Nielsen; Domenico Palli; Frederica Perera; Roel Vermeulen; Emanuela Taioli; Radim J Sram; Armelle Munnia; Fabio Rosa; Alessandra Allione; Giuseppe Matullo; Paolo Vineis

doi:10.1158/1055-9965.EPI-10-0314

Bulky DNA adducts in white blood cells: a pooled analysis of 3,600 subjects

Fulvio Ricceri, Roger W Godschalk, Marco Peluso, David H Phillips, Antonio Agudo, Panagiotis Georgiadis, Steffen Loft, Anne Tjønneland, Ole Raaschou-Nielsen, Domenico Palli, Frederica Perera, Roel Vermeulen, Emanuela Taioli, Radim J Sram, Armelle Munnia, Fabio Rosa, Alessandra Allione, Giuseppe Matullo, Paolo Vineis

23 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Cancer Epidemiology, Biomarkers & Prevention
Vol/bind	19
Udgave nummer	12
Sider (fra-til)	3174-81
Antal sider	8
ISSN	1055-9965
DOI	https://doi.org/10.1158/1055-9965.EPI-10-0314
Status	Udgivet - 1 dec. 2010

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10.1158/1055-9965.EPI-10-0314

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Ricceri, F., Godschalk, R. W., Peluso, M., Phillips, D. H., Agudo, A., Georgiadis, P., Loft, S., Tjønneland, A., Raaschou-Nielsen, O., Palli, D., Perera, F., Vermeulen, R., Taioli, E., Sram, R. J., Munnia, A., Rosa, F., Allione, A., Matullo, G., & Vineis, P. (2010). Bulky DNA adducts in white blood cells: a pooled analysis of 3,600 subjects. Cancer Epidemiology, Biomarkers & Prevention, 19(12), 3174-81. https://doi.org/10.1158/1055-9965.EPI-10-0314

Ricceri, F, Godschalk, RW, Peluso, M, Phillips, DH, Agudo, A, Georgiadis, P, Loft, S, Tjønneland, A, Raaschou-Nielsen, O, Palli, D, Perera, F, Vermeulen, R, Taioli, E, Sram, RJ, Munnia, A, Rosa, F, Allione, A, Matullo, G & Vineis, P 2010, 'Bulky DNA adducts in white blood cells: a pooled analysis of 3,600 subjects', Cancer Epidemiology, Biomarkers & Prevention, bind 19, nr. 12, s. 3174-81. https://doi.org/10.1158/1055-9965.EPI-10-0314

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title = "Bulky DNA adducts in white blood cells: a pooled analysis of 3,600 subjects",

abstract = "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.",

keywords = "DNA Adducts, Female, Humans, Leukocytes, Male, Seasons",

author = "Fulvio Ricceri and Godschalk, {Roger W} and Marco Peluso and Phillips, {David H} and Antonio Agudo and Panagiotis Georgiadis and Steffen Loft and Anne Tj{\o}nneland and Ole Raaschou-Nielsen and Domenico Palli and Frederica Perera and Roel Vermeulen and Emanuela Taioli and Sram, {Radim J} and Armelle Munnia and Fabio Rosa and Alessandra Allione and Giuseppe Matullo and Paolo Vineis",

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doi = "10.1158/1055-9965.EPI-10-0314",

language = "English",

volume = "19",

pages = "3174--81",

journal = "Cancer Epidemiology, Biomarkers & Prevention",

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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

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 -

Bulky DNA adducts in white blood cells: a pooled analysis of 3,600 subjects

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