Endocrine factors in human carcinogenesis

Endogenous hormones probably do not initiate cancer directly but may influence carcinogenesis by facilitation or inhibition of endogenous production of carcinogens; effects on the metabolic activation or inactivation of carcinogens; alteration of the susceptibility of tissues to the initiation of cancer; promotion of the development of clinical cancer from initiated cells; and (theoretically) alteration of the body's capacity to eliminate initiated cells. Evidence exists for a role of endogenous hormones in cancers of the salivary gland, colon and rectum, liver, gall-bladder, pancreas, breast, cervix uteri, corpus uteri, ovary, prostate, testis, kidney, thyroid and pituitary glands and malignant melanoma. Oestrogens are the most commonly implicated hormone, and there is sufficient evidence for their causal association with cancers of the breast and endometrium. The most commonly postulated mechanisms of action are alteration of the susceptibility of tissues to initiation, and promotion of the once-initiated cancer. In human beings and, to some extent, in animals it is difficult to distinguish between these two mechanisms, both of which are based on hormone-induced cell proliferation, because the time of initiation cannot be pinpointed. Environmental factors may influence carcinogenesis by effects on the production, transport, peripheral action, inactivation and excretion of endogenous hormones. Examples that illustrate some of these possibilities may be derived from the effects of diet on risk of breast, endometrial and thyroid cancers.