Role of Xenoestrogens and Endogenous Sources of Estrogens on the Occurrence of Premenopausal Breast Cancer in Iran

Breast cancer affects Iranian women one decade younger than their counterparts in other countries and the underlying risk factors have remained controversial. The aryl hydrocarbon receptor (AhR) mediates endocrine disruptive activities of polyaromatic hydrocarbons (PAHs) and dioxins, which may compromise ovarian functions of women in polluted environments. This study focused on tissue expression levels of AhR and associations with exposure to chemicals with estrogen-like activities (xenoestrogens) and other reproductive factors in premenopausal breast cancer patients. Fifty cases who underwent surgery from June 2009 to June 2010 were matched with 100 controls by age and hospital records. AhR overexpression was detected in 87% of epithelial cells of young breast cancer patients. Living near factories generating PAHs and dioxins was considered as a major risk factor in premenopausal breast cancer (p=0.001, OR=4.8). History of idiopathic infertility was identified as a second significant risk factor (p=0.002, OR=3.50), which could be affected by endogenous estrogen levels. Long term (>5 yrs) consumption of oral contraceptive pills was identified as the third most important risk factor (p=0.006, OR=2.27). Adiposity and abnormal weight gain after 18 years were considered as two major background factors, which may contribute to the levels of endogenous estrogens. Direct and indirect exposure to cigarette smoke (p=0.005, OR=1.43) was considered as a weak risk factor without association with AhR levels. It seems that AhR overexpression is affected by exposure to xenoestrogens and by adiposity. Early occurrence of breast cancer in Iran may be a result of interactions between hormonal and environmental factors.