Molecular epidemiology of lung cancer caused by inhalation carcinogens asbestos and smoking habit.

为了比较石棉纤维和烟草烟雾对肺腺癌发生的影响，我们检测了137例肺腺癌的LOH频率(以FAL值表示)和P53突变，并用正常肺组织石蜡切片测量石棉负荷(AB，每单位干燥肺组织的石棉小体数)。首先采用1990年代S手术切除的肺腺癌组织(n=46)。根据平均石棉体浓度(AB)(每克肺(干)数)，将病例分为三组：AB空(AB=0；n=22)、AB低(0&lt；AB&lt；1000；n=14)、AB高(AB&gt；=1000；n=11)。腺癌分化程度(好(WD)/中(MD)/差(PD))在AB阴性组为6/11/4，AB低分化组为6/8/0，高AB组为4/7/0。AB缺失组LOH频率为0.17，AB低组为0.07，AB高组为0.13。P53基因突变12例(27%)。突变频率与AB度…显著相关AB空组为16%(3/19)，AB低组为29%(4/14)，AB高组为45%(5/11)，P=0.006。其次，在4组(组1：AB=0，SI=0，组2：AB&gt；0，SI=0，组3：AB=0，SI&gt；0，组4 AB&gt；0，SI&gt；0)中，FAL在组4中最高，在其他3组中最低。P53突变率从第1组(21%)到第4组(50%)依次递增。与吸烟有关的突变，如结肠273和颠倒，常见于第3组和第4组，但偶尔也见于第1组和第2组。未发现石棉特异性突变。石棉没有改变好/中/差的比例。腺癌。结果表明：(1)吸烟和石棉联合作用对细胞的LOH频率和P53基因突变状态有明显影响；(2)石棉对烟草等遗传毒物损伤的细胞恶性进展的促进作用，而不是其本身对基因的损伤，因为石棉不会增加LOFT频率；(3)石棉的作用可能很差。与吸烟无关的腺癌是存在的，(4)在非吸烟者中发现的与吸烟相关的突变被认为是被动吸烟所致。较少

To compare carcinogenic effects on human lung between asbestos fibers and tobacco smoke in terms of genesis of adenocarcinoma, we examined LOH frequency (presented by FAL values) and p53 mutation in 137 lung adenocarcinomas, for which asbestos burden (AB, asbestos body numbers per unit dry lung tissue) was measured using paraffin blocks of normal lung tissue. At first, tissues of primary lung adenocarcinomas (n=46) resected in 1990's were used. The cases were divided into three groups based on mean asbestos body concentrations (AB) (numbers per g of lung (dry)) as follows AB null (AB =0; n=22), AB low (0<AB<1000; n=14).and AB high (AB>=1000; n=11). Differentiation grades of adenocarcinoma (well-(WD)/moderately-(MD)/poorly-(PD)) were 6/11/4 in AB null,6/8/0 in AB low, and 4/7/0 in AB high group. LOH frequency was 0.17 in AB null, 0.07 in AB low and 0.13 in AB high groups. p53 mutations were detected in 12 cases (27%). The frequency of the mutation significantly correlated with AB degree … More (16% (3/19) in AB null, 29% (4/14) in AB low, and 45% (5/11) in AB high group, p=0.006). Secondary, in the 4 groups (Group 1: AB =0, SI =0, Group 2: AB>0, SI =0, Group 3: AB =0, SI>0, Group 4 AB>0, SI>0), FAL was the highest in Group 4 and low in the other 3 groups. p53 mutation frequency increased sequentially from Group 1 (21%) to Group 4 (50%). Smoking related mutations such as colon 273 and transversions were often seen in Groups 3 and 4 but occasionally also in Groups1 and 2. No asbestos specific mutations were identified. Asbestos didn't change proportion of well/moderately/poorly diff. adenocarcinomas. Poorly-differentiate adenocarcinoma, usually seen in smokers, was found in 4 patients (F:M=3:1) of Group 1.These findings showed (1) combined effects of cigarette smoke and asbestos were evident in terms of LOH frequency and p53 mutation status, (2) asbestos seems to promote malignant progression of cells injured by genotoxic agents such as tobacco smoke rather than it injures genes by itself, because it doesn't increase LOFT frequency, (3) possibly, poorly-diff. adenocarcinoma, not related to smoking, exists, and (4) smoking-related mutations seen in non-smokers are deemed due to passive smoking. Less