Clock genes and cancer development in particular in endocrine tissues.

Circadian rhythms in central and peripheral level are operated by transcriptional/translational feedback loops involving a set of genes called 'clock genes' that are implicated in the development of several diseases including malignancies. Dysregulation of Clock system can affect cancer susceptibility by regulating DNA damage and repair mechanisms as well as apoptosis. A number of oncogenic pathways can be dysregulated via clock genes' epigenetic alterations including hypermethylation of clock genes' promoters or variants of clock genes. Clock genes disruption has been well studied in breast, lung, prostate cancer and hematological malignancies. However, it is still not entirely clear whether clock genes disruption is the cause or the consequence of tumourogenesis. Data in endocrine neoplasms are scarce. Recent findings suggest that clock genes are implicated in benign and malignant adrenocortical neoplasias. They are also associated with follicular and papillary thyroid carcinomas and parathyroid adenomas as well as pituitary adenomas and craniopharyngiomas. Dysregulation of clock genes is also encountered in ovarian and testicular tumours and may also be related with their susceptibility to chemotherapeutic agents. The most common clock genes that are implicated in endocrine neoplasms are PER1, CRY1 and in most cases their expression is down-regulated in tumoural compared to normal tissues. Although there is still a lot to be done for the better understanding of the role of clock genes in endocrine tumourigenenesis, existing evidence could guide research and help identify novel therapeutic targets aiming mainly at the peripheral component of the clock gene system.