This review is an attempt to comprehend the diverse groups of environmental chemical contaminants with a potential for pathogenesis of
breast cancer, their probable sources and the possible mechanisms by which these environmental contaminants act and interplay with other risk factors.
Estrogens are closely related to the pathogenesis of
breast cancer. Oxidative catabolism of
estrogen, mediated by various
cytochrome P450 enzymes, generates reactive
free radicals that can cause oxidative damage. The same
enzymes of estrogenic metabolic pathways catalyze biological activation of several environmental (
xenobiotic) chemicals.
Xenobiotic chemicals may exert their pathological effects through generation of reactive
free radicals. Breast tissue can be a target of several
xenobiotic agents.
DNA-reactive metabolites of different
xenobiotic compounds have been detected in breast tissue. Many phase I and II
xenobiotic metabolizing
enzymes are expressed in both normal and cancerous breast tissues. These
enzymes play a significant role in the activation/detoxification of
xenobiotic and endogenous compounds including
estrogens. More than 30 carcinogenic chemicals are present in tobacco
smoke; many of them are fat-soluble, resistant to metabolism and can be stored in breast adipose tissue. Similarly, pesticides are also known to cause oxidative stress; while some act as
endocrine disruptor, some are shown to suppress apoptosis in
estrogen sensitive cell lines. Reports have shown an association of smoking (both active and passive) and pesticides with
breast cancer risk. However, the issues have remained controversial. Different mutagenic substances that are generated in the cooking process e.g., heterocyclic
amines and
polycyclic aromatic hydrocarbons (PAHs) can be a threat to breast tissue. PAHs and
dioxins exert their adverse effects through the
aryl hydrocarbon receptor (AhR), which activates several genes involved in the metabolisms of
xenobiotic compounds and endogenous
estrogens. These chemicals also induce AhR-dependent
mitochondrial dysfunction. Many of the
environmental pollutants suppress the immune system, which are implicated to risk. A better understanding about the biological effects of different environmental carcinogenic compounds and determination of their impact on rising incidence of
breast cancer will be beneficial in improving preventive policy against
breast cancer.