Leukocyte polycyclic aromatic hydrocarbon–DNA adduct formation and colorectal adenoma

Abstract

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.

A review of airborne polycyclic aromatic hydrocarbons (PAHs) and their human health effects

“…Moreover, as PAHs have the potential to interfere with hormone systems, they can exert harmful effects on reproduction and immune function. As such, DNA damage induced by PAH exposure has been demonstrated by numerous authors (Garcia-Suastegui et al, 2011;Gunter et al, 2007;John et al, 2009). Long-term exposure to PAHs is suspected to raise the risks of cell damage via gene mutation and cardiopulmonary mortality (Kuo et al, 2003).…”

Polycyclic-Aromatic Hydrocarbon (Pahs) in Environment and Human Health: A Review.

“…Moreover, as PAHs have the potential to interfere with hormone systems, they can exert harmful effects on reproduction and immune function. As such, DNA damage induced by PAH exposure has been demonstrated by numerous authors (John et al, 2009;Gunter et al, 2007 and Garcia-Suastegui et al, 2011). Long-term exposure to PAHs is suspected to raise the risks of cell damage via gene mutation and cardiopulmonary mortality (Kuo et al, 2003).…”

Use of DNA adducts to identify human health risk from exposure to hazardous environmental pollutants: The increasing role of mass spectrometry in assessing biologically effective doses of genotoxic carcinogens

“…A recent study by Gunter et al have found that there was a 2.8-fold increase in the risk of colon adenoma in the quartile of individuals with the highest white blood cell PAH DNA adduct levels compared to the lowest quartile [93]. Many other associations have been drawn between adducts and biological effect in human studies, which have been well summarised in the review of Kyrtopoulos [94].…”