The dynamic and static modification of the epigenome by hormones: a role in the developmental origin of hormone related cancers.
There are numerous diseases associated with abnormal hormonal regulation and these include cancers of the breast and prostate. There is substantial evidence that early hormonal perturbations (in utero or during early development) are associated with increased disease susceptibility later in life. These perturbations may arise from exposure to environmental agents or endocrine disruptors which mimic hormones and disrupt normal hormonal signaling. Epigenetic alterations have often been proposed as the underlying mechanism by which early hormonal perturbations may give rise to disease in adulthood. Currently, there is minimal evidence to support a direct link between early hormonal perturbations and epigenetic modifications; or between epigenetic alterations and subsequent onset of cancer. Given that epigenetic modifications may play an important role in hormone-dependent cancers, it is essential to better understand the relationship between the hormonal environment and epigenetic modifications in both normal and disease states. In this review, we highlight several important studies which support the hypothesis that: hormonal perturbations early in life may result in epigenetic changes that may modify hormone receptor function, thereby contributing to an increased risk of developing hormone-related cancers.
Chiam
Karen
K
Dame Roma Mitchell Cancer Research Laboratories, Discipline of Medicine, The University of Adelaide, Hanson Institute, PO Box 14 Rundle Mall, Adelaide, South Australia, 5000, Australia.
Tilley
Wayne D
WD
Butler
Lisa M
LM
Bianco-Miotto
Tina
T
D044127:Epigenesis, Genetic; D006728:Hormones / Q000502:physiology*; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics*
D006728:Hormones