Human Clock Genes and Cancer

Abstract

Modern social life often demands aberrant light exposures (i.e., jet lag, shift work, or nocturnal life style), which results in desynchronization and misalignment of circadian rhythms. Experimental and epidemiological data suggest that circadian disruption, caused by genetic manipulations or forced light/dark conditions, promotes cancerogenesis. Human genetic studies highlight the contribution of individual clock genes to this process, though the exact function is somewhat controversial. Multiple reports demonstrate an association of genetic variations within clock genes with risk of tumor development. Mutations or deregulated expression of clock genes are frequently detected in different tumors and often show correlation with cancer progression and patient prognosis. Cellular studies report contradictory results that clock genes can inhibit as well as support tumor growth and proliferation in different cells. Clock genes appear to have multifaceted functions during cancer development and can act both as tumor suppressors or promote cancerogenesis depending on the particular type of tumor. However, the exact conditions and factors which determine such behavior remain elusive and must be investigated in future studies.