Further analysis of the relationship between the epidemiological and hormonal aspects of 6 human neoplasias with special emphasis on the presentation of the topological features of oncogene activation tumor suppressor gene inactivation of individual neoplasias

Abstract

The purpose of this study was to test the validity of the steroid carcinogenesis hypothesis by comparatively investigating the endocrinological and epidemiological aspects of cancers of the breast, uterine cervix, endometrium, stomach, esophagus and ovary. The emphasis of this study was placed on the extraction of the information on the topological feature of oncogene activation-tumor suppressor gene inactivation for each of 6 neoplasias using the data stock of the age-adjusted incidence rates (AAIRs) of 19 neoplasias from 47 population units of the world. Our investigation was started on the basis of the recognition that the world statistics data of cancer risk should include information on the interaction of oncogene activation-tumor suppressor gene inactivation for each human neoplasia, and that the sophisticated application of statistical analysis technics may allow us to assess separately the implications of oncogene activation and tumor suppressor gene inactivation in the genesis of a given neoplasia. In designing mathematical strategies, we had in mind the premise that oncogene activation and tumor suppressor gene inactivation represent 2 distinct entities in the world of chemistry, and that they should have each their own equilibrium models with 2 distinct equilibrium points. The details of the mathematical principles and procedures are presented in the text. The results were as follows: i) There was a good agreement of results between the observed value and the expected value of thermodynamics as regards the location of the equilibrium point in both instances - a finding to support the validity of our mathematical strategies. ii) One of our mathematical strategies (the use of the original coordinates and its variant coordinates in parallel) was found to be useful for assessing separately the implication of oncogene activation (the original coordinates) and that of tumor suppressor gene inactivation (the variant coordinates). iii) The correlation study of the endocrinological data with the epidemiological data in breast cancer strongly suggests the possibility that sex steroid may play a cardinal role in the oncogene activation at the initiation step of breast carcinogenesis. iv) Evidence is available to indicate that glucocorticoid under certain circumstances may play a crucial role in the process of tumor suppressor gene inactivation at the promotion step of breast carcinogenesis. v) The philosophical distinction between the steroid carcinogenesis theory and the random mutation criminal theory of carcinogenesis is discussed in the light of recent information on chemical carcinogenesis.