Hormone related cancers

Prostate Cancer. Evidence that phytoestrogens can influence the incidence of male-speciflc diseases is restricted to prostate cancer, and is largely of an observational nature. In the UK, prostate cancer is the most common hormone-related cancer in men. However, like breast cancer in women, it is comparatively rare as a clinically evident disease in men living in Asian countries. 

In recent years, concern that chemicals might inadvertently be disrupting the endocrine system of humans and wildlife has increased. The concerns regarding exposure to these endocrine disrupters are based on adverse effects observed in certain wildlife, fish, and ecosystems increased incidences of certain endocrine-related human diseases and adverse effects observed in laboratory animals exposed to certain chemicals. The main effects reported in both wildlife and humans concern reproductive and sexual development and function altered immune system, nervous system, and thyroid function and hormone-related cancers. Endocrine dismption is not considered a toxicological endpoint in its own right, but a functional change or toxicological mode(s) of action that may lead to adverse effects. Endocrine dismpters are addressed further in Section 4.11. 

Hormone-related cancers of the breast, ovary, endometrium, and prostate have been reported to vary by as much as 5 to 20-fold between populations. Migrant studies indicate that the difference is largely attributable to environmental factors rather than genetics [219,220]. The highest rates of these cancers are typically observed in populations with Western lifestyles that include relatively high fat, meat-based, low fiber diets, whereas the lowest rates are typically observed in Asian populations with Eastern lifestyles that include plant-based diets with a high content of phytoestrogens [219,221]. 

A different form of toxicity occurs in the estrogen and androgen receptors when environmental chemicals have the ability to bind to them. Acting both as agonists or antagonists, these so-called endocrine disruptors are responsible for a number of hormone-related cancers, in addition to their roles in adversely affecting sexual development and reproductive fertility. 

A, Dunn BK, Wickerham DL, Ford LG. Prevention of hormone-related cancers Breast cancer. J Clin Oncol 2005 23 357-67. 

Pressler H, Sissung TM, Venzon D, Price DK, Figg WD (2011) Expression of OATP family members in hormone-related cancers potential markers of progression. PLoS One 6 e20372... 

Terry, P. D., Rohan, T. E., and Wolk, A. (2003). Intakes of fish and marine fatty adds and the risks of cancers of the breast and prostate and of other hormone-related cancers A review of the epidemiologic evidence. Am. J. Nutr. 77,532-544. 

Products and Uses A trace mineral that occurs naturally in whole wheat bread and pastas, Brazil nuts, pork, lamb, and beef The recommended daily allowance is 55 megs. A 1996 study showed that selenium reduced some cancer incidence by 67%. Unfortunately, this was an all-male study. Research still needs to be done in women, on hormone-related cancers. 

Perhaps the strongest driver for the increase in consumption of soyfoods is perceived health benefits. Consumption of soyfoods has been linked to a number of benefits most prominently prevention of heart disease, prevention of colon cancer and hormone related cancers e.g., breast and prostate), and alleviation of women s post-menopausal health problems (menopausal symptoms and osteoporosis). For the... 

Breast cancer is one of the most common forms of cancer affecting women and, in Western countries, the incidence is rising. The risk of breast cancer increases markedly with age, although a decrease in the rate occurs after the menopause, suggesting that development is hormone-dependent. To date, a number of hormone-related risk factors have been identified (Bingham et al, 1998). Countries such as Japan have relatively low rates of breast cancer, which have been associated with consumption of a diet high in soy foods. Currently, however, the data from epidemiological studies is inconclusive. 

The delicate balance maintained by these factors is altered in patients with cancer by two principal mechanisms tumor production of humoral factors that alter calcium metabolism (humoral hypercalcemia) and local osteolytic activity from bone metastases.27 Humoral hypercalcemia causes around 80% of all hypercalcemia cases and is mediated primarily by systemic secretion of parathyroid hormone-related protein... 

First we shall describe the effects of tamoxifen, a first-generation SERM used as adjuvant treatment in women with breast cancer, on uterine leiomyomas and endometriosis. Considerable space will be devoted to raloxifene, a second-generation SERM administered for the prevention and treatment of postmenopausal women recently tested for the treatment of these two sex-hormone-related diseases. Unfortunately, at present no or very little data are available on the new third-generation SERMs such as lasofoxifene, idroxifene, droloxifene, ospemifene, azomifene, fulvestrant, and MDL 103.323. 

Hormones regulate many important bodily functions and are also associated with cancer. One of the first hints of the relationship of hormones to cancers was the observation that nuns had a greater incidence of breast cancer. This was naturally related to the nuns not having children and now we know that breast cancer may be hormone related. Since then there have been numerous studies on the use of birth control with cancer, childbirth, and most recently hormone replacement association with cancer. In males there is ongoing study of the hormones and prostate cancer. While it is clear that hormones and cancer are related, the exact characterization of this relationship is still unclear. 

Use of Hormones in Nonendocrine Disease. There are many examples of how various hormones and hormone-related drugs can be used to treat conditions that are not directly related to the endocrine system. For instance, certain forms of cancer respond to treatment with glucocorticoids (see Chapter 36). Drugs that block the cardiac beta-1 receptors may help control angina and hypertension by preventing excessive stimulation from adrenal medulla hormones (epinephrine, norepinephrine see Chapters 21 and 22). 

Rabbani, S. A., Gladu, J., Harakidas, R, Jamison, B. and Goltzman, D. (1999). Over-production of parathyroid hormone-related peptide results in increased osteolytic skeletal metastasis by prostate cancer cells in vivo. Inti. J. Cancer 80, 257-264. 

Parathyroid Hormone-Related Protein PTHrP was discovered in 1987 by investigators studying the mechanism by which certain cancers produce humoral hypercalcemia of malignancy (HHM). ... 

Blind E. Humoral hypercalcemia of malignancy role of parathyi oid hormone-related protein. Recent Results Cancer Res 1994 137 20-43. 

Burtis WJ, Brady TG, Orlofif JJ, Ersbale JB, WarreU RP Jr, Olson BR, et al. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. 

Ralston SH> Danks J, Hayman J, Fraser WD, Stewart CS, Martin TJ. Parathyroid hormone-related protein of malignancy immunohistochemical and biochemical studies in normal and hypercalcemic patients with cancer. J Clin Pathol 1991 44 472-6. 

A second member of the parathyroid hormone family, parathyroid hormone-related protein (PTHrP), is quite similar to PTH in amino acid sequence and protein structure. Like PTH, it activates the parathyroid hormone receptor causing increased bone resorption and renal tubular calcium reabsorption. Increased serum concentrations of parathyroid hormone-related protein are the predominant cause of hypercalcemia in cancer patients with solid tumors. This observation led to its discovery and to the elucidation of its many cellular functions in normal tissues. In contrast to PTH, which is expressed only in parathyroid glands, PTHrP is detected in many tissues in fetuses and adults it is found in epithelia, mesenchymal tissues, endocrine glands, and the central nervous system. This protein is also the principal regulator of placental calcium transport to the fetus. 

Danks JA, Ebeling PR, Hayman J, et al. Parathyroid hormone related protein Immunohistochemical localization in cancers and in normal skin. J Bone Miner Res. 1989 4 273-278. 

Some cancers may cause hyper-calcaemia. In many cases this is due to the secretion of parathyroid hormone related protein, PTHrP, so-called because of its relationship with PT H both in its structure and function. 

K. Griffiths, W.B. Peeling, M.E. Harper, P. Davies and C.G. Pierrepont, in Hormonal Management of Endocrine-Related Cancer, ed. B.A. Stoll (Lloyd-Luke, London) (1981) pp. 131-147. 

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