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 (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-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 10(8) nucleotides) than polyp-free controls (median, 1.2 adducts per 10(8) 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 10(8) 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; P(trend) = 0.048) for risk of colorectal adenoma. These data support a link between PAH exposure and colorectal adenoma.