title: Insights into genetic and epigenetic determinants with impact on vitamin d signaling and cancer association studies: the case of thyroid cancer.
abstract: 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.
authors.affiliation: 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.
authors.forename: Grégoire B
authors.initials: GB
authors.lastname: Morand
authors.affiliation: 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.
authors.forename: Sabrina Daniela
authors.initials: SD
authors.lastname: da Silva
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, McGill University , Montreal, QC , Canada.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hier
authors.affiliation: 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.
authors.forename: Moulay A
authors.initials: MA
authors.lastname: Alaoui-Jamali
keywords: VDR; cancer susceptibility; genome-wide studies; thyroid cancer; vitamin D