Hormones and carcinogenesis

Abstract

Hormones are important regulators of growth. By stimulating proliferation, hormones may increase the risk of mutation and at the same time stimulate the replication of the mutated cell. Thus, hormones are complete carcinogens. A direct carcinogenic effect of oestrogen in man is known from the occurrence of vaginal carcinomas in girls born of mothers who were treated with oestrogen during pregnancy. There are also experimental animal studies indicating that even peptide hormones may induce malignant tumours.An excellent example is the so-called enterochromaffin-like cell (ECL-cell) carcinoid of the stomach, which is caused by hypergastrinaemia and where the pathogenesis is diffuse hyperplasia, linear and nodular hyperplasia, dysplasia (with micronodules), intramucosal carcinoid, and invasive carcinoid. This sequence of events can be followed not only histopathologically but also by means of image DNA cytometry of the nuclei of the ECL-cells. As soon as clear-cut neoplasia is present, the cytometric DNA distribution pattern switches from the normal diploid type to an aneuploid one. The Endocrine-Related Cancer (1998) 5 45-48 hyperplastic lesions are all reversible, as soon as the hypergastrinaemia is eliminated. H L Waldum et al.: Hormones and carcinogenesis 46Mutations occur at cell divisions with a certain frequency. Mutagens increase the risk of mutation via a direct effect on the genes. Whether a mutation induced by a mutagen gives rise to a clinically overt tumour depends on the type of mutation and also on the replication of the mutated cell. Hormones may stimulate the growth of cells including mutated cells, and they have, therefore, been thought to be important co-carcinogens. By stimulating mitosis, hormones increase the risk of mutation solely by increasing the number of cell divisions (Ames & Gold 1990). Normally most mutations are corrected by DNA repairing mechanisms (Lindahl 1976). These repairing processes take time, and there is reason to believe that speeding up the rate of cell division may increase the risk of permanent mutations being transferred to daughter cells. Thus, hormones may not only be co-carcinogens, but in reality be among the most important carcinogens by increasing the risk of mutations in their normal target cells and at the same time stimulating the growth of the mutated cells. Hormones and growth controlThe lipid soluble steroid hormones affect the growth of their target cells by interaction with hormone responsive elements in the nucleus, affecting the regulation of gene expression (Reichel & Jacob 1993). Peptide hormones influence cellular growth by interacting with their cell membrane receptor, which, via a cascade reaction, affects gene expression. Among the peptide hormones a growth stimulatory effect has been attributed mainly to the hormones interacting with receptors coupled to the formation of inositol trisphosphate (Berridge & Irvine 1984), and only to a lesser extent to hormones coupled to adenylate cyclase (MacManus & Whitfield 1969). We (Brenna & Waldu...

Clinical and histopathological tumour progression in ECL cell carcinoids (“ECLomas”)

“…However, the number of HDC IR cells was distinctly lower, and did not exceed 20% in any part of the tumour. In the neoplastic cells of the recurrent neoplasm and in those of the lymph node metastases, the proportion of HDC experimentally (16)(17)(18). The clinical observations give full support to these experimental data.…”

Role of Hormones in Oral Squamous Cell Carcinoma - An Update

“…Literature search fetched up few researches and reviews linking the role of hormones and oral cancer [6][7][8][9]. Endogenous and exogenous hormones act by exciting cell proliferation thus increasing the risk of mutations in their normal target cells as well as stimulating the growth of the mutated cells thereby providing chance for random genetic errors [5,10].…”