Polycyclic Aromatic Hydrocarbons (PAHs)
CATEGORY: IARC probable, NTP reasonably anticipated, Endocrine disruptor
USED IN: Products of combustion in cigarette smoke, diesel exhaust, grilled meats, and coal and coke-burners
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous byproducts of combustion, from sources as varied as coal and coke burners, diesel-fueled engines, grilled meats and cigarettes. PAH residues are often associated with suspended particulate matter in the air, and thus inhalation is a major source of PAH exposure (Bonner, 2005). In the Silent Spring Institute study of environmental contaminants in house dust, three PAHs (pyrene, benz[a]anthracene and benz[a]pyrene) were found in more than three-quarters of the homes tested (Rudel, 2003). Although they are still found extensively in suspended particulate matter, federally imposed standards on vehicular emissions have led to a significant decrease in PAH release by vehicles from their highest levels in the 1970s (Beyea, 2008).
Like many other environmental chemicals that are associated with breast cancer risk, PAHs are lipophilic and are stored in the fat tissue of the breast. PAHs have been shown to increase risk for breast cancer through a variety of mechanisms. The most common PAHs are weakly estrogenic (estrogen mimicking), due to interactions with the cellular estrogen receptor (Pliskova, 2005). However, the major receptor-directed pathway is different, with PAHs associating with a protein called the aryl hydrocarbon receptor (AhR), initiating a series of cell changes that lead to altered cell signaling and ultimately to increases in DNA mutations (Kemp, 2006; Santodonato, 1997). PAHs can also be directly genotoxic, meaning that the chemicals themselves or their breakdown products can directly interact with genes and cause damage to DNA (Ralston, 1997).
Several epidemiological studies have implicated PAH exposure in increased risk for breast cancer. One of the studies from the Long Island Breast Cancer Study Project found that women with the highest level of PAH-DNA adducts had a 50 percent increased risk of breast cancer. PAH-DNA adducts are indicators of problems in DNA repair in cells, one of the early hallmarks of tumor development (Gammon, 2002). In an earlier report, researchers explored the presence of PAH-DNA adducts in breast samples taken from women diagnosed with cancer as compared with those diagnosed with benign breast disease. Cancerous samples were twice as likely to have PAH-DNA adducts as were benign samples (Rundle, 2000). Follow-up work indicates that those women who had higher levels of PAH adducts may not necessarily have had higher exposures to PAHs, but instead had particular genetic profiles that encourage the deficits in DNA repair (Gammon, 2008). Other studies support the presence of different genetic profiles for women who have increased numbers of PAH-DNA adducts, including polymorphisms in genes involved in cell metabolism, tumor-suppressor mechanisms and DNA repair (Gammon, 2008; Mahadevan, 2005). Differences were not found in the profiles of genes whose products are involved in the activation and deactivation of the PAHs themselves (McCarty, 2009).
Occupational exposure studies have looked at workers exposed regularly to gasoline fumes and vehicular exhaust, major sources of PAHs (as well as benzene). These occupational exposures are associated with an increased risk of breast cancer for pre-menopausal women (Petralia, 1999) and also for men. In the case of male breast cancer, PAHs may increase the risk of breast cancer specifically in men carrying a BRCA1 or BRCA2 mutation (Palli, 2004).
A recent case-control study in western New York indicated that very early life exposure (around the time of birth) to high levels of total suspended particulates, a proxy measure for PAH levels, is associated with increased risk of breast cancer in post-menopausal women (Bonner, 2005). An extension of this study, examining PAH exposures at critical times in women’s reproductive histories, demonstrated a relationship between particulate exposures at the time of menarche (first period) and incidence of pre-menopausal breast cancer, and a relationship between exposure levels at the time of first birth and risk of post-menopausal breast cancer (Nie, 2007). The results are complex, but all contribute to our understanding that exposures to environmental toxicants at critical periods of breast development can influence later cancer risk.
The studies above all looked at breast cancer incidence. One recent analysis examined the relationship between PAH-adduct levels and mortality among women who had been diagnosed with breast cancer. In an extension of the Long Island study described above, researchers found no overall relationship between survivorship and PAH-DNA-adduct levels. Looking more closely at groups of women who had undergone different types of treatments, however, revealed a twofold increase in deaths from breast cancer among women with high PAH-DNA adduct levels who had received radiation treatment; this was offset partially by an increased survival for women with adducts who had received hormone therapy (Sagiv, 2009).
