Cholesterol and Prostate Cancer

Prostate cancer (PC) is the most common nonskin cancer in American men. In North America, about 10% of men are diagnosed with PC during their lifetime. Laboratory studies of PC models and human tissues, and observational studies of nutrition in migrants, have provided evidence that a Western diet, rich in fat and cholesterol, increases PC risk. This hypothesis is supported by some observational studies of potential chemo-preventive effects of cholesterol-lowering drugs. Cholesterol, a neutral lipid synthesized in mammalian cells via the mevalonate pathway, is essential for maintenance of cell membrane integrity, androgen synthesis, and other cell processes. It has been known for decades that PC cells and tissues can accumulate excess cholesterol. In this chapter we discuss certain aspects of cholesterol homeostasis as they relate to PC, and the likely role of cholesterol dysregulation in PC incidence and progression. We also consider the implications of perturbations in cholesterol metabolism during disease progression, and in the emergence of aggressive PC variants that are less dependent on the androgen axis.