Kodama M, Murakami M, Kodama T
Kodama Research Institute of Preventive Medicine, Nagoya, Japan.
Anticancer Res. 1997 May-Jun;17(3C):2285-92.
The cancer risk changes of 19 human neoplasias over time and space, as expressed in terms of the logarithm of age-adjusted incidence rate (log AAIR), were found to hold a linear correlation with each other--a finding suggesting that the distribution pattern of log AAIR data sets of 2 cancers, when plotted on a two dimension diagram, may show a good fitness to the chemical equilibrium model a product of the law of mass action. On the basis of the statistical analysis of the data, we reached the conclusion that the risk changes of a given neoplasia in space represents the function of the centripetal force of an activated oncogene and the centrifugal force of an inactivated tumor suppressor gene, both of which should cooperate with each other to create a thermodynamic equilibrium under the law of mass action. The purpose of this study was to test the contribution of the oncogene-tumor suppressor gene complex to the sex discrimination of cancer risk in 19 human neoplasias. The results obtained are as follows: a) the correlation coefficient r seq of the sequential regression analysis, as applied to 47 log AAIR data sets of one tumor pair, served as a criterion in testing the balance of power between oncogene activation and tumor suppressor gene inactivation. Sole activation of the oncogene should give an r seq value of -1.0, whereas sole inactivation of the tumor suppressor gene should give an r seq value of +1.0. b) Esophageal cancer and laryngeal cancer, two sex-discriminating tumors with distinct male predominance were each associated with differential implications of the oncogene-tumor suppressor gene complex between the male and female populations: in both tumors, the male populations were associated with a complex of activated oncogene and inactivated tumor suppressor gene, whereas the female population was associated with another complex of weakly activated (esophageal cancer) or non-activated (laryngeal cancer) oncogene and inactivated tumor suppressor gene, as assessed by the r seq criteria. c) The intersex correlation of cancer risk in both esophageal cancer and laryngeal cancer for 47 populations throughout the world, was rather weak, when compared with other members of human neoplasias. The intersex difference of r seq as expressed in terms of t value of Student's t test for each of 19 human neoplasias, was negatively correlated with the correlation coefficient r of the intersex regression analysis with the same 47 populations. It was indicated that a change in the intersex linkage of cancer risk may be related to the differential implication of the oncogene-tumor suppressor gene complex in carcinogenesis. In summary, we conclude that the hormonal milieu of the host plays a cardinal role as the modifier of the oncogene-tumor suppressor gene impact.
研究发现，19种人类肿瘤的癌症风险随时间和空间的变化（以年龄调整发病率对数表示，即log AAIR）彼此呈线性相关——这一发现表明，将两种癌症的log AAIR数据集绘制在二维图上时，其分布模式可能与化学平衡模型（质量作用定律的产物）具有良好的拟合度。基于对数据的统计分析，我们得出结论：特定肿瘤在空间上的风险变化代表了激活的癌基因的向心力和失活的肿瘤抑制基因的离心力的函数，这两者应在质量作用定律下相互协作以建立热力学平衡。本研究的目的是检验癌基因 - 肿瘤抑制基因复合体对19种人类肿瘤癌症风险性别差异的影响。获得的结果如下：a）应用于一对肿瘤的47个log AAIR数据集的序列回归分析的相关系数r seq，用作检验癌基因激活和肿瘤抑制基因失活之间力量平衡的标准。仅癌基因激活应给出r seq值为 -1.0，而仅肿瘤抑制基因失活应给出r seq值为 +1.0。b）食管癌和喉癌是两种具有明显男性优势的性别差异肿瘤，在男性和女性人群中，癌基因 - 肿瘤抑制基因复合体的影响各不相同：根据r seq标准评估，在这两种肿瘤中，男性人群与激活的癌基因和失活的肿瘤抑制基因复合体相关，而女性人群与弱激活（食管癌）或未激活（喉癌）的癌基因和失活的肿瘤抑制基因的另一种复合体相关。c）与人类其他肿瘤相比，全球47个人群的食管癌和喉癌癌症风险的两性间相关性相当弱。根据学生t检验的t值表示的19种人类肿瘤中每种肿瘤的r seq两性间差异，与相同47个人群的两性间回归分析的相关系数r呈负相关。这表明癌症风险两性间联系的变化可能与癌基因 - 肿瘤抑制基因复合体在致癌过程中的不同影响有关。总之，我们得出结论，宿主的激素环境作为癌基因 - 肿瘤抑制基因影响的调节因子起着主要作用。
