Carcinogenesis Advance Access originally published online on February 2, 2007
Carcinogenesis 2007 28(7):1426-1429; 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, National Institutes of Health, Division of Health and Human Services, Bethesda, MD 20852, USA
2 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
3 Carcinogen-DNA Interactions Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Division of Health and Human Services, Bethesda, MD 20892, USA
4 Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, MA 02115, USA
5 Division of Environmental Epidemiology, Institute of Risk Assessment Sciences, University of Utrecht, Utrecht, NL-3508 TD, The Netherlands
6 Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
* To whom correspondence should be addressed. Tel: +718 430 3089; Fax: +718 430 8780; Email: mgunter{at}aecom.yu.edu
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 using an antiserum elicited against DNA modified with (±)-7ß,8
-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene 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 (OR) 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 OR 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.
Abbreviations: BP, benzo[a]pyrene; BPDE, 7ß,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene; BPdG, 10ß-(deoxyguanosin-N2-yl)-7ß,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene; CI, confidence interval; CIA, chemiluminescence immunoassay; OR, odds ratio; PAH, polycyclic aromatic hydrocarbon
These authors contributed equally to this study. Received December 4, 2006; revised January 19, 2007; accepted January 23, 2007.