Carcinogenesis Advance Access published online on February 2, 2007
Carcinogenesis, doi:10.1093/carcin/bgm022
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Published by Oxford University Press 2007.
Leukocyte Polycyclic Aromatic Hydrocarbon-DNA Adduct Formation and Colorectal Adenoma
1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
2 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA
3 Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
4 Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, MA, USA
5 Institute of Risk Assessment Sciences, University of Utrecht, Utrecht, The Netherlands
6 Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
Correspondence to: Dr. Marc Gunter, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300, Morris Park Avenue, Bronx, New York, NY, 10461, USA
Consumption of charbroiled red meat and meat-derived polycyclic aromatic hydrocarbons (PAHs) has been associated with risk of colorectal adenoma, a precursor of colorectal cancer. Furthermore, leukocyte PAH-DNA adduct levels have been demonstrated to increase in response to charbroiled red meat intake but to date there have been no studies that have investigated the relationship between leukocyte PAH-DNA adduct levels and risk of colorectal adenoma. We investigated the relation of leukocyte PAH-DNA adduct formation and colorectal adenoma in a clinic-based case-control study of colorectal adenomas. The study comprised 82 cases of colorectal adenoma and 111 polyp-free controls, none of whom were current smokers. Leukocyte PAH-DNA adducts were measured by a sensitive chemiluminescence immunoassay (CIA) using an antiserum elicited against DNA modified with (±)-7ß,8
-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE) that recognizes several PAHs bound to human DNA. Leukocyte PAH-DNA adduct levels were higher among colorectal adenoma cases (median, 1.4 adducts per 108 nucleotides) than polyp-free controls (median, 1.2 adducts per 108 nucleotides) (P = 0.02). There was a positive association between PAH-DNA adduct level and adenoma prevalence: each unit increase in PAH-DNA adduct level (per 108 nucleotides) was associated with an odds ratio of 1.5 (95% confidence interval [CI], 1.1-2.2). In addition, a comparison of the lowest quartile for PAH-DNA adduct level with the highest quartile yielded an odds ratio of 2.8 (95%CI, 1.2-6.5; Ptrend = 0.048) for risk of colorectal adenoma. These data support a link between PAH exposure and colorectal adenoma.
Key Words: Polycyclic Aromatic Hydrocarbon • DNA adduct • chemiluminescence immunoassay • colorectal adenoma
M.J Gunter and R.L Divi contributed equally to this manuscript Received December 4, 2006; revised January 19, 2007; accepted January 23, 2007.