Height, Leg Length, and Cancer Risk: A Systematic Review

Associations between height and cancer risk have been reported in a number of prospective studies (1, 2). Taller individuals appear to be at increased risk. Furthermore, ecologic analyses indicate that geographic patterns of cancer incidence and mortality are associated with variations in population height (3-5). The most consistent associations have been found in relation to breast cancer (6-8), although associations have also been reported for many other cancer sites. Therefore, common mechanisms may underlie these associations, but their precise nature remains unclear. Models of cancer pathogenesis suggest that cancer arises as a result of DNA damage at a number of specific loci important in the regulation of the cell cycle or DNA repair (9, 10). While specific oncogenes, tumor suppresser genes, and cancer susceptibility genes have been identified, it has become increasingly apparent that epigenetic pathways also underlie the development of some malignancies. Several mechanisms may be common to many different cancers. For example, angiogenesis (the formation of new blood vessels) is an absolute requirement for the growth of all solid tumors (11). Similarly, apoptosis is a mechanism for eliminating damaged or dangerous cells from the body, and thus it provides a natural defense against cancer. The most potent cell survival factor controlling apoptosis is insulin-like growth factor I (IGF-I). Raised levels of IGF-I and reduced levels of its main binding protein, insulin-like growth factor (IGF)- binding protein 3, may diminish this defense against a range of cancers. In support of this notion, recent prospective research has demonstrated that raised levels of IGF-I are associated with increased risks of prostate (12-14), breast (15), and colorectal (16, 17) cancers.