ELSEVIER Lung Cancer 15 (1996) 139-157

LUNG CANCER

Abstracts

Prevention

Lung cancer in women: Selected topics in epidemiology and prevention Beck&t WS. Yale Universiry. School of Medicine, I35 College Street, New Haven. CT06510. J Women’s Health 1995;4:63743.

Cancer is the second most frequent cause of death in women (after cardiovascular disease), and lung cancer is the most frequent cause of cancer death in women. The biologic characteristics of lung cancers do notdiffermarkedlyb&weenwomenandmen, althoughoneepidemiologic study bas suggested increased susc+ibility of women to the carcinogenic effects of cigarette smoking, the primary cause of the majority of lung cancers. In industrialixcd nations such as the United States, women have always smoked less than men andcontinue to smokeless than men. Lung cancer incidence and mortality for women lagged behind those for men for most of this century, but they are rising more rapidly as the result of the latency period following a sharp inc- in smoking in women decades ago. Currently, about 23% of adult women smoke. It is projected based on current smoking patterns that lung cancer mortality will plateau around 2010 and then begin to decline. The rate of smoking cessation in teenage women in recent years lagged slightly behind that of men. In all other age categories, smoking among women has been less. Other less frequent causes of lung cancer include radon, asbestos, ether industrial chemicals, and environmental tobacco smoke. Lung cancer is an infrequent occurrence among women in cultures where cigarette smoking is uncommon. However, tobacco producers appear to be targeting advertising to women nonsmokers in some countries, as they have in the United States. Where cigarette smoking becomes more prevalent among women, incidence and mortality from smoking will undoubtedly also increase in direct proportion.

Epidemiology and etiology

Pulmonary dust retention in silicotics with and without lung cancer Loosereewanich P, Ritchie AC, Armstrong B, Begin R, Muir DCF, Dufresne A. Department of Occupational Health, Faculty of Medicine, McGill University, 3450 University Street, Montreal. Que. H3A 2A7. Appl Occup Environ Hyg 1995; IO: 1104-6.

Recent epidemiological studies suggest a possible increased risk of lung cancer in silicotic patients. To address the question of lung dust concentrations between silicotics with and without lung cancer, we used transmission electron microscopy and energy dispersive spectroscopy to analyze 41 lung tissue samples comprising 22 noncancer silicotics, 9 silicotics with lung cancer, and 10 accidental deaths without lung fibrosis at autopsy (referred to later as background group). Comparison

between the background group and the pooled silicotic group revealed significantly higher lung dust concentrations and largerparticlediameters of silica, feldspar, clay, mica, and total particles in the latter group (p < 0.05). When lung dust burdens of the noncancer silicotics and lung cancer silicotics were compared, the noncancer group had higher, but not significantly, geometric mean concentrations of total particles (16 x 10’ compared with 10 x 1V particleslmg), silica (4 x 106 compared with 2 x lob), clay (4 x 1V compared with 3 x I@), feldspar (3 x 10’ compared with 2 x lo&), mica (0.6 x 10’) compared with 0.4 x Iti), iron (0.6 x 106compared with 0.3 x 106). and metal-rich particles (0.7 x 10’ compared with 0.2 x lob). Both groups had similar particle sizes and mineral compositions. In conclusion, the preliminary results confirm the presence of large quantities of dust of various sorts in silicotics. There were no statistically significant differences between the particle concentrations in the noncancer silicotic group and the lung cancer silicotic group, although the mean levels were higher in the noncancer group. Further investigation involving analysis of additional lung samples of each group, mineralogical characterization of silica particles by X-ray diffraction, and association between lung burden, dust exposure, and clinical findings is underway.

A doseresponse relationship between the frequency of p53 mutations and tobacco consumption in lung cancer patients Kondo K, Tsuzuki H, Sass M, Sumitomo M, Uyama T, Monden Y. Second Department of Surgery. School of Medicine, University of Tokwhima. Kuramoto-rho. Tokushima City, Tokushima 770. J Surg Oncol 1996;61:20-6.

Mutations of the ~53 tumor suppressor gene are frequent in lung cancers. It is suggested that p53 mutations are associated with smoking- induced lung carcinogenesis. We examined p53 mutations in 53 lung cancers by analyzing reverse transcription-polymerase chain reaction- single strand conformation polymorphism (RT-PCR-SSCP) to ascertain the association between p53 mutations and smoking. Twenty five (47 W) of 53 lung cancers carried p.53 mutations. A discriminant analysis showed that the Brinkman index (0.156) and gender (0.140) significantly influenced ~53 mutations. Furthermore, there was a dose-response relationship between the quantity of cigarettes consumed and the frequency of ~53 mutations in lung cancer patients (P < 0.001). In patientswithadenocarcinoma, thefrequencyofp53 mutationscorrelated with the amount of the tobacco smoked (P < 0.05). We suggest that the p53 gene is a target of particular carcinogen in tobacco smoke.

The effect of tobacco on lung cancer risk depends on CYP2D6 activity Bouchardy C, Benhamou S, DayerP. Geneva CancerRegistry. Boulevard de la Cluse 55, 1205 Geneva. Cancer Res 1996;56:251-3.

The genetically determined P450 CYP2D6 activity is suspected to

140 Abstracts /L.tatg Cancer I5 (19%) 139-157

be involved in lung carcinogenesis by activating carcinogens contained in tobacco smoke. Therefore, lung cancer risk should depend on both smoking exposure and CYPZD6 activity. The extent to which CYP2D6 activity, determined by using dextromethorphan, could modify the effectoftobaccowasevaluated fromastudyon 128 lung cancers and 157 controls. A strong interaction was observed; the effect of tobacco on lung cancer risk rose with increasing CYP2D6 activity (P < 0.001). Increasing levels of smoking increased lung cancer risk only among smokers with the highest CYP2D6 activity, and CYP2D6 was a risk factor only among heavy smokers. Smokers with both the highest CYP2D6 activity and daily tobacco consumption were at very high risk for lung cancer. These results may explain discrepant results of previous studies on the association between CYPZD6 activity and lung cancer.

Altered cJun expression: An early event in human lung carcinogenesis Szabo E, Riffe ME, Steinberg SM, Birrer MJ, Linnoila RI. Cancer Prevention/Control Division, Biomarkers/Prevention Res. Branch, National Cancer Institute. 9610 Medical Center Drive, RockviNe, MD 20850. Cancer Res 1996;56:305-15.

Although the c-jun oncogene is an integral part of the AP-1 transcriptional complex implicated in the process of tumor promotion, its role in the pathogenesis of human tumors is unknown. We analyzed the expression and function of cJun in 110 non-small cell lung cancer (NSCLC) primary and metastatic tumors, histologically atypical areas from the surrounding lung, and 10 NSCLC cell lines to examine the role of cJun in lung carcinogen&s. cJun was expressed in primary and metaatatic lung tumors in 31% of cases, with no association with survival. Whereas normal conducting airway and alveolar epithelia in general did not express clun by immunohistochemistry, histologically atypical areas were frequently positive for cJun, regardless of the status of the corresponding tumor. Multiple members of the jun andlos gene families were frequently expressed at the mRNA level in vitro, with detectable functional activity (as defined by AP-l- specific DNA binding and/or tramactivation of an AP-l-driven reporter construct) present mall 10 NSCLC cell lines examined. Although tumor- promoting phorbol esters had little effect on c-jun expression, serum stimulation generally resulted in significant c-jun induction in NSCLC cell lines. These data show that cJun expression is altered early during human lung carcinogenesisandthatclun may hmctionasamediatorofgrowth factor signals in NSCLC.

P53 in squamous metaplasia: A marker for risk of respiratory tract carcinoma Boers JE, Ten Velde GPM, Thumiissen FBJM . Department ofPathology, University of Limburg, P.O. Box 5600, 6202 AZ Maastricht. Am J Respir Crit Care Med 1996;153:411-6.

Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premalignant lesion. Recently, presumably irreversible genetic alterations have been demonstrated in squamous metaplasia with dysplasia in lung-resection specimens. The genetic alterations were closely similar to those in adjacent bronchial carcinoma. There remains the question of which changes in squamous metaplastic lesions are premalignant, and which of these changes predict the occurrence of carcinoma of the respiratory tract. The purpose of this study was to determine the positive predictive value for respiratory-tract malignancy of thegradeofdysplasia, p53 immunoreactivity, proliferative activity, and B&2 in bronchial biopsy specimens exhibiting squamous metaplasia. Bronchial biopsies of 51 patients with squamous metaplasia diagnosed between 1982 and 1993 were used. Immunohistochemistry was done after microwave pretreatment of the biopsy specimens. Only unequivocally stainednuclei werecounted. Normal bronchial epithelium

obtained from autopsies was used as a control. In 31 patients, a synchronous or metachronous carcinoma was present (61%). Positive p53 immunoreactivity was found in 22 of the 51 patients (43 W). The positive predictive values of ~53 and of a high grade of dysplasia for carcinoma of the respiratory tract were 91% and 8096, respectively. Although the hyperproliferative state of squamous metaplastic lesions was clearly established, neither the percentage of MIB-1 labelling nor themitoticindexdistinguishedpatientgmupswithandwithoutcaminoma. No increased Bcl-2 immunostaining was found in squamous metaplasia. In conclusion, p53 immunoreactivity in squamous metaplastic lesions in bronchial biopsies is a marker of carcinoma of the respiratory tract.

Extensive areas of aneuploidy are present in the respiratory epithelium of lung cancer patients Smith AL, Hung J, Walker L, Rogers TE, Vuitch F, Lee E, Gazdar AF. Simmons Cancer Center, Vniv TxSouthwestem Med CtrDallas, 5323 Harry Hines Blvd. Dallas, TX 75235-8593. Br I Cancer 1996;73:203- 9.

According to the field cancerisation theory the entire upper aerodigestive tract has been mutagenised, thereby placing the affected individual at risk for the development of one or more cancers. To investigate this concept we studied the respiratory epithelium in lungs bearing cancer, including bronchi, bmnchioles and alveoli. After identifying preneoplastic and preinvasive lesions by light microscopy, we determined the DNA content of their nuclei in Feulgen-slained sections using a high-performance digitised image analyser. Archival material from 35 resected cases of non-small-cell lung cancer (NSCLC) was selected, including 16 central rumours (mainly squamous cell carcinomas) and 19 peripheral tumours (mainly adenocarcinomas) and five resected cases of metastatic tumour from extrathoracic primary sites. Of the NSCLCs, 3 l/35 (89 W) were aneuploid, as were 60 96 of the metastases fromextrathoracic sites. Multiple, focal areas ofpreneoplasia or preinvasive carcinoma were present in the selected cases. The lesions ranged in severity from hyperplasia through metaplasia and dysplasia to carcinoma in situ. Aneuploid preinvasive lesions were not noted in association with the four diploid tumours but were present only when the accompanying NSCLC was aneuploid. With both central and peripheral tumours, aneuploid preneoplastic lesions were more frequent in the peripheral parts of the lung (bronchioles or alveoli) than in the central bronchi. Both the degree and incidence of aneuploidy increased with progressive severity of morphological change. Aneuploidy was not found in preinvasive lesions accompanying the Eve metastatic cases. Chu fmdingsprovidestrongsuppott fortheconceptoflieldcancerisation.

The tendency of lung cancer crude mortality rate in Ecuador. A comparative analysis with other malignant neoplasias during the decade 19844993 Freire AX, Freire NV. Servicio de Neumologia, SOLCA, Apt. Postal 09-06, 2436 Urdesa. Guayaquil. Gncologia (Ecuador) 1995;5:5-8.

This study gives a global figure for Ecuador of the secular trends of lung, stomach, leukemia, cervical and breast cancer during the decade 1984-1993. Lung cancer crude mortality rate revealed an ascending trend as compared to the other malignancies that remain stable during this period. Data was obtained from the National Census and Statistics Institute (INEC) from the latest Birth and Deaths summary publication. This is the most complete mortality source available in Ecuador. The study reveals that the malignant effects of cigarette consumption are already present in our country.

Recent data on cancer due to asbestos in Germany RoslerJA, WoitowitzHJ. InstituteandOutpatient Clinic, Occupational