Roles of transbronchial factors including cigarette smoke and asbestos for rapidly increasing lungcancer

为了调查日本迅速增加的肺癌的原因，我们分析了基因变化和致癌吸入物，包括吸烟和石棉。我们检查了原发性肺癌（20世纪50年代9例，70年代52例，90年代60例）肺内石棉沉积。在20世纪50年代、70年代和90年代，平均石棉体浓度（每克肺（干）的数量）分别为559、1804和563。与90年代相比，70年代浓度显著升高（p<0.005）。由于日本的肺癌发病率从1950年到1990年一直在上升，石棉暴露被认为不是肺癌增加的主要原因。此外，我们比较了20世纪70年代原发性和转移性肺腺癌之间肺中的石棉浓度。此外，我们还检测了1990年代肺腺癌的分化等级、LOH频率（以FAL值表示）和p53突变，根据石棉体浓度（AB，数/干g）将其分为3组：零AB组（AB=0, n=21）、低AB组（0<AB<1000, n=14）和高AB组（1000=<AB, n=l1）。20世纪70年代男性原发癌的AB值为2050，显著高于转移性癌的703，但在女性中差异不显著。在这三组中，好/中等/差。分别是6/11/4 6/8/0 4/7/0；FAL值分别为0.17、0.07、0.13；p53突变频率分别为3/19、4/14、5/11。无论石棉水平如何，轻度和中度分化癌占主导地位，FAL值小于吸烟者（0.21,n=66）。有趣的是，高AB组的p53突变频率明显高于零AB组（p =0.006）。

To investigate the causes of rapidly increasing lung cancer in Japan, we analysed both genetic changes and carcinogenic inhalants including smoking and asbestos. We examined primary lung cancers (9 in 1950s, 52 in 1970s and 60 1990s) in terms of asbestos deposition in the lung. Mean asbestos body concentrations (numbers per g of lung (dry)) were 559, 1804 and 563 in 1950s, 1970s and 1990 s, respectively. Statistically significant elevation in the concentration of 1970s was noted as compared to that of 1990s (p<0.005). Since the lung cancer incidence in Japan has been rising from 1950 to 1990, asbestos exposure is not thought to be a main cause of lung cancer increase. Further, we compared asbestos concentrations in the lung between primary and metastatic lung adenocarcinomas in 1970s. Also, we examined differentiation grades, LOH frequency (presented by FAL values) and p53 mutations in lung adenocarcinomas in 1990s, subclassified to 3 groups by asbestos body concentration (AB, numbers/dry g) : zero AB group (AB=0, n=21), low AB group (0<AB<1000, n=14 and high AB group (1000=<AB, n=l1). AB in primary cancers in 1970s was 2050 in males, significantly higher than that of metastatic cancers, 703, although the difference was not significant in females. In the three groups, well/moderate./poor. were 6/11/4, 6/8/0, 4/7/0 ; FAL values were 0.17, 0.07, 0.13 ; and p53 mutation frequencies were 3/19, 4/14, 5/11. Regardless of asbestos levels, well and moderatelydifferentiated carcinomas were predominant and FAL values were smaller than that for smokers (0.21, n=66). Interestingly, p53 mutation frequency was significantly more frequent in high AB group than in zero AB group (p =0.006).