Why Hormones Protect Against Large Bowel Cancer: Old Ideas, New Evidence

摘要

Colorectal cancer (CRC) is second only to lung cancer as the leading cause of cancer mortality in men and women, and remains a significant cause of morbidity. Accumulating evidence from observational, clinical, and laboratory studies indicates that hormones reduce large bowel cancer risk. Recently, questions have arisen regarding which hormones are germane, and in what milieu they are relevant. In this chapter, we consider the genesis of this hypothesis, its studies in humans, and biological pathways that might explain recent and past findings, including new genetic and epigenetic mechanisms. Other perturbations in metabolizing enzymes responsible for estrogen metabolisms and the conversion of progesterone to estrogens may be relevant, although specific polymorphisms contributing to variations in hormone concentrations have not been directly related to CRC risk (1). We also provide some new evidence on the long-term effects of hormones on specific subtypes of large bowel tumors, and on CRC mortality, further supporting putative roles for hormone effects.