Xenoestrogens challenge 17β-estradiol protective effects in colon cancer

Several epidemiological, cellular, and molecular studies demonstrate the role of environmental chemicals with endocrine disrupting activities, typical of Westernized societies, in the pathogenesis of numerous diseases including cancer. Nonetheless this information, the design and execution of studies on endocrine disruptors are not yet cognizant that the specific actions of individual hormones often change with development and ageing, they may be different in males and females and may be mediated by different receptors isoforms expressed in different tissues or at different life stages. These statements are particularly true when assessing the hazard of endocrine disruptors against 17β-estradiol (E2) actions in that this hormone is crucial determinant of sex-related differences in anatomical, physiological, and behavioral traits which characterize male and female physiology. Moreover, E2 is also involved in carcinogenesis. The oncogenic effects of E2 have been investigated extensively in breast and ovarian cancers where hormone-receptor modulators are now an integral part of targeted treatment. Little is known about the E2 preventive signalling in colorectal cancer, although this disease is more common in men than women, the difference being more striking amongst pre-menopausal women and age-matched men. This review aims to dissect the role and action mechanisms of E2 in colorectal cancer evaluating the ability of estrogen disruptors (i.e., xenoestrogens) in impair these E2 actions. Data discussed here lead to define the possible role of xenoestrogens in the impairment and/or activation of E2 signals important for colorectal cancer prevention.