An overview of the polymorphisms of circadian genes associated with endocrine cancer

A major consequence of the world industrialized lifestyle is the increasing period of unnatural light in environments during the day and artificial lighting at night. This major change disrupts endogenous homeostasis with external circadian cues, which has been associated to higher risk of diseases affecting human health, mainly cancer among others. Circadian disruption promotes tumor development and accelerate its fast progression. The dysregulation mechanisms of circadian genes is greatly affected by the genetic variability of these genes. To date, several core circadian genes, also called circadian clock genes, have been identified, comprising the following: ARNTL, CLOCK, CRY1, CRY2, CSNK1E, NPAS2, NR1D1, NR1D2, PER1, PER2, PER3, RORA, and TIMELESS. The polymorphic variants of these circadian genes might contribute to an individual's risk to cancer. In this short review, we focused on clock circadian clock-related genes, major contributors of the susceptibility to endocrine-dependent cancers through affecting circadian clock, most likely affecting hormonal regulation. We examined polymorphisms affecting breast, prostate and ovarian carcinogenesis, in addition to pancreatic and thyroid cancer. Further study of the genetic composition in circadian clock-controlled tumors will be of great importance by establishing the foundation to discover novel genetic biomarkers for cancer prevention, prognosis and target therapies.SM-S would like to thank the grant awards from SEIOMM (2017) and SEEN (2018). JJ-L was funded by a Ramon y Cajal Research Program from the Spanish Ministry of Economy, Industry and Competitiveness (grant ref. number YC-2014-16536); the grant ref. BFU2016-77243-P; by the CSIC—intramural grant ref. 201540E065; and by the EU Marie Curie Research Program FP7-PEOPLE-2011-IOF, grant ref. PIOF-GA-2011-301550. All authors thank Michela Verbeni for the English language edition performed on the manuscript