Endocrine dismodulation and cancer.
OBJECTIVE
Carcinogenesis has generally been viewed as a genomic disease resulting from genetic mutations occurring at critical locations in the genome in a particular sequence. In the last 10 years, scientists have increasingly identified changes in the levels, frequency and types of endocrine hormones as important contributors to the major cancers faced by western populations such as breast cancer (estrogen, progesterone, prolactin), prostate cancer (estrogen, testosterone), endometrial cancer (estrogen) and thyroid cancer (TSH, T3, T4). This manuscript summarizes cancer mechanisms linked to changes in endocrine function and discusses tools for analyzing and understanding the associated data.


CONCLUSIONS
A number of chemicals in the environment mimic the role of hormones to bind to receptors (e.g. phytoestrogens as estrogen mimics), alter signaling pathways (e.g. retinoids), inhibit steroid hormone synthesis (such as some fungicides) or alter steroid hormone metabolism (such as TCDD altering the metabolism of both estrogen and thyroid hormones). Genomic and non-genomic endocrine signaling pathways are extensively present in the body and function in a complicated fashion. In order to fully understand the basis for endocrine-induced cancers, one must simultaneously study the various receptors, ligands, enzymes, other proteins within different organs which all contribute to endocrine system function. Also, cross-talk between endocrine systems is common and is key to understanding a potential role of light-dark cycles on human cancer risks.


CONCLUSIONS
Mechanism-based mathematical models are the only analysis tool available to address all aspects of these complicated networks.
Portier
Christopher J
CJ
Environmental Toxicology Program, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA. portier@niehs.nih.gov
D000818:Animals; D006728:Hormones / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000503:physiopathology*; D009490:Neurosecretory Systems / Q000502:physiology*
D006728:Hormones