Hormones in the aetiology of cancer

Different hormones and their related growth factors play a variety of roles in carcinogenesis in a number of malignancies, including cancer of the:

In these sites the cancer results from excessive hormonal stimulation of relevant target cells. These effects occur independently of other aetiological agents like chemical carcinogens or ionizing radiation.

In the 1960s, daughters of women treated with diethylstilbestrol (DES) during pregnancy were found to develop vaginal adenocarci-noma as they reached menarche, an indication that hormones could be both directly carcinogenic and involved in tumour promotion. Now it seems DES causes persistence of Mullerian duct remnants in the vagina, and these are activated with the hormonal changes of puberty. There is some evidence that exposure of the male foetus to high levels of oestrogens can also have carcinogenic effects later in life, with increased risk of maldescent and testicular cancer.

The role of hormones in promoting cancer is further shown by the fact that women whose ovaries never secrete steroid hormones do not develop breast cancer. Hormonal factors associated with an increased risk of breast cancer are:

♦ Late age at first pregnancy.

As with breast cancer, an increased risk of ovarian cancer is associated with nulliparity. It is thought that promoters of ovarian cancer are growth factors that control normal repair after ovulation (the fewer numbers of ovulations, the less risk of ovarian cancer). In endometrial cancer the risk of disease is related to exposure of the endometrium to oestrogens, unopposed by the effects of progesterone (HRT, obesity, sequential oral contraceptives, late menopause).

In laboratory animals, prostate cancer can be produced by exposure to large doses of exogenous testosterone; in man, castration at an early age provides lifelong protection from this common tumour. However, circulating testosterone levels have not shown consistent differences between prostate cancer cases and controls, and studies of alteration in androgen receptors have so far been inconclusive.

Pimentel, E. (1987) Hormones, grown factors and oncogenes. Chapman and Hall, London.

Hodges, G.M., Rowlatt, C. (1993) Developmental biology and cancer. Chapman and Hall, London.

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