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与内分泌癌相关的昼夜节律基因多态性概述。

An Overview of the Polymorphisms of Circadian Genes Associated With Endocrine Cancer.

作者信息

Morales-Santana Sonia, Morell Santiago, Leon Josefa, Carazo-Gallego Angel, Jimenez-Lopez Jose C, Morell María

机构信息

Proteomic Research Service, San Cecilio University Hospital, Instituto de Investigación Biosanitaria de Granada (Ibs.GRANADA), Granada, Spain.

Department of Genetics, University of Cambridge, Cambridge, United Kingdom.

出版信息

Front Endocrinol (Lausanne). 2019 Feb 26;10:104. doi: 10.3389/fendo.2019.00104. eCollection 2019.

Abstract

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: , and . 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.

摘要

全球工业化生活方式的一个主要后果是,白天环境中自然光时间增加,夜间人工照明增多。这一重大变化扰乱了内源性稳态与外部昼夜节律线索,而这与影响人类健康的疾病风险增加有关,其中主要包括癌症等。昼夜节律紊乱会促进肿瘤发展并加速其快速进展。昼夜节律基因的失调机制受到这些基因遗传变异性的极大影响。迄今为止,已经鉴定出几种核心昼夜节律基因,也称为生物钟基因,包括以下几种: ,以及 。这些昼夜节律基因的多态性变体可能会增加个体患癌症的风险。在这篇简短的综述中,我们重点关注了与生物钟相关的基因,这些基因通过影响生物钟,最有可能影响激素调节,从而成为内分泌依赖性癌症易感性的主要因素。我们研究了影响乳腺癌、前列腺癌和卵巢癌发生的多态性,此外还研究了胰腺癌和甲状腺癌。通过为发现用于癌症预防、预后和靶向治疗的新型遗传生物标志物奠定基础,进一步研究生物钟控制肿瘤中的基因组成将具有重要意义。

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