Morand Grégoire B, da Silva Sabrina Daniela, Hier Michael P, Alaoui-Jamali Moulay A
Department of Otolaryngology-Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, McGill University , Montreal, QC , Canada ; Departments of Medicine and Oncology, Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University , Montreal, QC , Canada.
Department of Otolaryngology-Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, McGill University , Montreal, QC , Canada.
Front Oncol. 2014 Nov 4;4:309. doi: 10.3389/fonc.2014.00309. eCollection 2014.
Vitamin D is a key regulator of calcium metabolism and has been implicated as a cancer preventive agent. However, clinical studies have revealed conflicting results on its cancer preventive properties, attributed in part to multiple metabolic and regulatory factors susceptible to affect individual responses to exogenous vitamin D. Vitamin D is obtained from dietary sources and sun exposure, which depends on numerous parameters such as skin type, latitude, and lifestyle factors. Focusing on thyroid cancer (TC), we document that genetic and epigenetic determinants can greatly impact individual response to vitamin D and may outweigh the classical clinical correlative studies that focus on sun exposure/dietary intake factors. In particular, genetic determinants innate to host intrinsic metabolic pathways such as highly polymorphic cytochromes P450s responsible for the metabolic activation of vitamin D are expressed in many organs, including the thyroid gland and can impact vitamin D interaction with its nuclear receptor (VDR) in thyroid tissue. Moreover, downstream regulatory pathways in vitamin D signaling as well as VDR are also subject to wide genetic variability among human populations as shown by genome-wide studies. These genetic variations in multiple components of vitamin D pathways are critical determinants for the revaluation of the potential preventive and anticancer properties of vitamin D in TC.
维生素D是钙代谢的关键调节因子，并且被认为是一种癌症预防剂。然而，临床研究显示其癌症预防特性的结果相互矛盾，部分原因是多种代谢和调节因素容易影响个体对外源性维生素D的反应。维生素D可从饮食来源和阳光照射中获取，而这取决于众多参数，如皮肤类型、纬度和生活方式因素。聚焦于甲状腺癌（TC），我们证明遗传和表观遗传决定因素会极大地影响个体对维生素D的反应，并且可能比专注于阳光照射/饮食摄入因素的经典临床相关性研究更为重要。特别是，宿主内在代谢途径固有的遗传决定因素，如负责维生素D代谢激活的高度多态性细胞色素P450s，在包括甲状腺在内的许多器官中表达，并可影响维生素D与其在甲状腺组织中的核受体（VDR）的相互作用。此外，全基因组研究表明，维生素D信号传导以及VDR中的下游调节途径在人群中也存在广泛的遗传变异性。维生素D途径多个组成部分的这些遗传变异是重新评估维生素D在TC中的潜在预防和抗癌特性的关键决定因素。
