378 Abstracts/Lung Cancer 14 (19%) 377-408

through retinoid receptors could contribute to lung carcinogenesis. Using a lung carcinogen&s model consisting of normal, premalignant, and malignant HBE cells, we examined all-tram retinoic acid (t-RA)- induced changes in cellular growth. These studies revealed that t-RA treatment inhibited the growth of normal HBE cell& but premalignant and malignant HBE cells were relatively resistant to t-RA. Coincident with the development of retinoid refractoriness, basal expression of the retinoic acid nuclear receptor8 (RAR-8) increased. Analysis of receptor function by gel shift and transient transfection assays of normal, premalignant, and malignant HBE cells demonstrated that receptor- DNA binding and transcriptional activation properties were intact in the t-RA-refractory malignant HBE cells. To compare these findings to NSCLCs in patients, we investigated retinoid receptor expression in NSULC biopsies. A subset of the tllmors expressed RAR-D, reflecting the RAR-8 expression observed in the malignant HBE cells in culture. These findings demonstrate that retinoid receptor tinction was intact in the t-RA-refractory malignant HBE cell line, suggesting that the defect in retinoid signaling in this lung carcinogenesis model is not intriusic to the retinoid receptors.

Lymphoepithelioma-like carcinoma of the lung: Analysis of two cases for Epstein-Barr virus infection Higashiyama M, Doi 0, Kodama K, Yokouchi H, Tateishi R, Horiuchi K, Mishima K. Department of 7lwracic Surgery, Center for Adult Disemes, Nakamichi l-3-3, Higashinairku, Osaka 537. Hum Pathol 1995;26: 1278-82.

Lymphoepithelioma-like carcinoma, which is an uncommon histological type of epithelial tumor, has been described as being closely associated with Epstein-Barr virus (EBV) infection in organs other than the lung. Recently, we experienced two surgically resected cases of pulmonary tumors mimicking lymphoepithelioma-like carcinoma. Both cases contained EBV DNA genomes as shown by polymerase chain reaction (PCR) using EBV DNA-specific primers, onepositivefor EBV DNA in virtually all cancer cells, and the other showing positive hybridization in a small number of cancer cells by in situ hybridization (ISH) using digoxigenin-labeled oligonucleotide probes for each of EBV DNA for EBV DNA. EBV-encoded RNA-l (EBER-1) was typically detected in one case. These results are highly suggestive of EBV-associated tumors in oneof thecurrent cases, although in the other case, no such close association was determined. It seems that lymphoepithelioma-like pulmonary carcinoma, vjhich seems extremely unusual, may beclosely associated with EBV infection in tumorigenesis.

CYFQD6 genotype and lung cancer risk according to histologic type and tobacco exposure Stucker 1, Cosme J, Laurent Ph, Cenee S, Beaune Ph. Bignon J et al. U Rech Epidemiol Stats Environ Sante, INSERM U 170. 16 Avenue Paul- Vailkmt Couturier, 94807ViIlejuifCedex. Carcinogenesis 1995;16:2759- 64.

Polymorphism for CYP2D6 was determined generically as part of a hospital-based case-control study. The cases were males with a histologically confirmed lung cancer diagnosis, < 75 years old, and no previous cancer diagnosis. Male controls were matched for age, hospital and residence area. This study includes 301 cases and 310 controls. A DNA bank was established for 547 patients (89.5 %), and genotypes for CYP2D6 were differentiated by the Helm and Meyer method for the DNA samples of 249 cases and 271 controls. Among the cases, the frequ&ncies of homozygous for the wild-type (EM), heterozygous (HEM) and homozygous for the mutant alleles (PM) were 62 R , 32 % and 7 96; among the controls: 57 %, 37 46 and 6 46. Using EM as the reference, and adjusting for age, hospital and residence, we estimated the odds ratios for the HEM group and the PM group at 0.8 (95 46 CI

[0.5-1.21) and 1.1 (95% CI [0.5-2.41) respectively. The PM frequency among the cases of adenocarcinoma was hvice as high as among the controls (OR = 1.8, 95% CI [0.74.9]). This result was not observed among squamous and small cell carcinoma (OR = 0.7, 95 % CI [0.3- 1.81). Twelve different case-control studies on CYP2D6 and lung cancer have so far been performed; the ORs they estimate range from 0.1 to 2.0, with a median value of - 0.6. This result lends some support to the hypothesis that belonging to the PM group is associated with a slight protective effect against lung cancer, but does not take into account the possibility that results may vary according to histologic type. In this context, the suggestion of a positive relationship between CYP2D6 and adenocarcinoma seems to us to merit investigation.

Distinct mutational spectrum of the p53 gene in lung cancers from Chinese women in Hong Kong Takagi Y, Koo LC, Osada H, Ueda R, Kyaw K, Ma C-C et al. Lab. of lJltra.wucture Research. Aichi Cancer Center Research Inst., Chikura- ku, Nagoya 464. Cancer Res 1995;55:5354-7.

Accumulating evidence suggests that the ~53 gene is a good target for molecular epidemiological studies to search for risk factors in carcinogenic events. The lung cancer incidence for females in Hong Kong is unusually high, ranking among the highest in the world despite a low percentage with a history of smoking. To gain insights into possible etiological risk factors responsible for this high incidence, we examined ~53 mutations in 35 lung cancer specimens from Chinese females living in Hong Kong and compared them with 35 matched eases from Japanese women as well as previously reported ~53 mutations in the world literature. p-53 mutations in exons 5-8 were present in 20 and 31% of the Hong Kong and Japanese cases, respectively. Notably, single-base deletions within runs of identical bases were observed in 3 (43 46) of the 7 mutations in the Hong Kong cases, in contrast to the absence of such mutations in the controls and the extreme scarcity in the literature, suggesting that distinct environmental andtorgenetic factor(s) might be involved. Although the frequent occurrence of characteristic single-base deletions could be a reflection of mutator mutations leading to inefficient mismatch repair of slipped strand mispairings, none of the lung cancer specimens exhibited such microsatellite instabilities.

Descriptive epidemiological study on lung cancer Wang X-X, Wang Q-S. Tianjin Municipal Ogice, Cancer Prevention and Treatment, ‘lanjitt. Chin J Clin Oncol 1995;22:709-12.

This paper depicted the epidemic pattern of lung cancer in Tianjin as compared with that of selected areas in the world. The age standardized incidence rate of lung cancer was 44.50/100,000 for male and 33.71 100,000 for female in Tianjin Urban area during the period of 1983- 1987. It ranked first both in maIes and females of a11 cancer sites. In comparison with other 166 areas/population in the world where data are available, Tianjin ranked 109th in the male and 15th in the female. Over the last 20 years, lung cancer incidence rate increased in most areas/ populations, especially in female. Due to the difficulty in combating environmental pollution and the cigarette smoking solution in China, incidence rate of hmg cancer is expected to go up further in this country.

Correlation of DNA adducts in blood mononuclear cells with tobacco carcinogen-induced damage in human lung Wiencke JK, Kelsey KT, Varkonyi A, Semey K, Wain JC, Mark E et al. Dept. ofEpidemiology/Bios~atistics, VCSF, 500 Parntwu~ Avenue. San Francisco, CA 94143-05&I Cancer Res 1995;55:4910-4.

The formation of carcinogen-DNA adduces within the respiratory epithelium is thought to be a critical factor in the induction of lung cat~cer

from tobacco smoke. A reliable surrogate measure of carcinogen damage to the lung would be of great value in molecular epidemiological