Phosphorus and Malignancies

Cancer, in its origins, is a disease of the cell born of acquired or inherited genetic mutations. Progression to malignancy is a complex and partially understood multistage process involving genetic and/or somatic mutations and influenced by environmental factors and the functions of neighboring and distant cells and tissues. Lifestyle factors, such as diet, can have a strong influence over initiation and progression of cancer in part through changes in functional genomic output. Phosphorus, usually in the form of inorganic phosphate (Pi), is abundant in the Western diet and represents an element that might alter cell behavior through direct effects on cellular and molecular functions as well as changes in the micro- and macroenvironment. Pi therefore represents a dietary element that has the potential to influence multiple facets of cancer etiology and progression. Given the significance of Pi for cell function and energy metabolism, it is somewhat surprising that relatively little is known about the potential effects of changes in cellular and serum Pi on cell growth and transformation related to cancer. This chapter will review the consequences of changes in serum Pi levels and dietary Pi consumption on direct cellular and molecular functions as well as the potential effects of Pi-responsive endocrine/paracrine/autocrine factors on noncancerous cell growth and cancerous transformation to malignancy.