ABSTRACT
Complex diseases such as cancer are influenced by numerous risk factors, including genetic makeup, environmental stresses, and lifestyle choices such as diet. These risk factors combine to alter cellular and molecular function, ranging from uncontrolled proliferation to evading programmed cell death to invasion and migration, ultimately resulting in the myriad of negative health consequences that define cancer. Lifestyle choices such as diet represent risk factors that can be reasonably controlled 14and manipulated for disease prevention and general health benefit. However, identifying and understanding the contribution of individual components of the human diet to health and pathological conditions represents a tremendous challenge, particularly in the context of a disease such as cancer, which can arise in most tissues and has a multitude of underlying etiologies. One dietary component that has recently gained attention as a potential cancer-modifying factor is inorganic phosphate (Pi), which is highly abundant in the Western diet. Cell-based studies have identified Pi as a factor that can alter cell behavior, including proliferation, metabolism, and migration, through direct effects on cellular and molecular functions, as well as changes in the micro and macro environment. Pi therefore represents a dietary element that has the potential to influence multiple facets of cancer etiology and progression. Indeed, recent studies utilizing murine cancer models have identified a diet high in Pi as a contributing risk factor for cancer initiation and progression relative to a reduced Pi diet. This chapter will discuss the modulating effects of dietary Pi consumption on cancer evaluated using preclinical models and will consider the potential mechanisms by which cancer might be influenced by varying Pi consumption, including cell autonomous, autocrine, paracrine, and endocrine effects.
