title: The Role of Cholesterol in Cancer.
abstract: The roles played by cholesterol in cancer development and the potential of therapeutically targeting cholesterol homeostasis is a controversial area in the cancer community. Several epidemiologic studies report an association between cancer and serum cholesterol levels or statin use, while others suggest that there is not one. Furthermore, the Cancer Genome Atlas (TCGA) project using next-generation sequencing has profiled the mutational status and expression levels of all the genes in diverse cancers, including those involved in cholesterol metabolism, providing correlative support for a role of the cholesterol pathway in cancer development. Finally, preclinical studies tend to more consistently support the role of cholesterol in cancer, with several demonstrating that cholesterol homeostasis genes can modulate development. Because of space limitations, this review provides selected examples of the epidemiologic, TCGA, and preclinical data, focusing on alterations in cholesterol homeostasis and its consequent effect on patient survival. In melanoma, this focused analysis demonstrated that enhanced expression of cholesterol synthesis genes was associated with decreased patient survival. Collectively, the studies in melanoma and other cancer types suggested a potential role of disrupted cholesterol homeostasis in cancer development but additional studies are needed to link population-based epidemiological data, the TCGA database results, and preclinical mechanistic evidence to concretely resolve this controversy. Cancer Res; 76(8); 2063-70. ©2016 AACR.
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Omer F
authors.initials: OF
authors.lastname: Kuzu
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Noory
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Department of Pathology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Department of Dermatology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Penn State Hershey Melanoma Center, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Penn State Melanoma Therapeutics Program, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. The Foreman Foundation for Melanoma Research, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. gprobertson@psu.edu.
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Robertson
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D002784:Cholesterol