title: Topological evidence of differential oncogene activation-tumor suppressor gene inactivation features in 10 human neoplasias, as revealed by sequential regression analysis of world cancer incidence data.
abstract: Recent progress in the molecular biology of cancer research indicates that oncogene activation and tumor suppressor gene inactivation are the two key events in the carcinogenesis of humans as well as of animals. The purpose of this investigation was to assess separately the impact of oncogene activation and tumor suppressor gene inactivation on the genesis of a given neoplasia using the log-transformed age-adjusted incidence rates (log AAIRs) data from 47 cancer registration areas world wide. In practice, the sequential regression analysis test was applied to each of 15 (male) or 16 (female) tumor pairs, in which the neoplasia in question (marker tumor) was designated as the common x partner in the calculation of the 1st order regression equation. The correlation coefficient of the sequential regression analysis, r seq, served as an index of fitness to the equilibrium models of both oncogene activation and tumor suppressor gene inactivation, in which the expected values of r seq for sole oncogene activation and sole tumor suppressor gene inactivation were each -1.00 and +1.00. The calculation results with the sequential regression analysis were given as the profile of 15 (male) or 16 (female) r seq data for each marker tumor. The r seq profile of a given neoplasia was also prepared using each the original coordinates (the "Org" coordinates) and 2 variant coordinates (the "Rect" coordinates and the "Para" coordinates). The "Rect" and the "Para" coordinates were so designed as to allow their x-axes to run at a right angle and parallel to the regression line of the tumor pair data block. Results obtained are as follows: a) The "Org" coordinates gave an oncogene activation- type r seq profile for each of all marker tumors tested; b) The "Rect" coordinates gave a tumor suppressor inactivation-type r seq profile for each of all marker tumors tested; c) The r seq profile of the "Para" coordinates was classified as of the intermediate type as regards the direction (+ or -) as well as the amplitude of r seq values; d) Remarkable amplification of oncogene activation was noted in the r seq profile of the dominant gender as compared with the recessive gender in 3 cancers with sex-discriminant cancer risks (cancers of the esophagus, liver and breast). In summary, the use of the "Org"- and the "Rect"-coordinates in the sequential regression analysis was found to be useful for assessing separately the impact of oncogene activation and tumor suppressor gene inactivation on the genesis of a tumor. Amplification of oncogene activation was very often responsible for the emergence of sex difference in cancer risk. The association of the 2 coordinates with the 2 contrasting r seq profiles was explained by the topology of the tumor pair data distribution in the 2 dimensional diagram. Finally, the findings with sex-differential tumors are discussed in the light of the steroid carcinogenesis hypothesis.
authors.affiliation: Kodama Research Institute of Preventive Medicine, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kodama
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: T
authors.initials: T
authors.lastname: Kodama
mesh_terms: D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D014943:Global Health; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D012042:Registries; D012044:Regression Analysis; D012737:Sex Factors