LUNG CANCER

ELSEVIER Lung Cancer 14 (1%) 377-408

Abstracts

Epidemiology and etiology

Lung cancer risk in African-Americans in relation to a race- speciFic CYPlal polymorphism LondonSJ, Daly AK, FairbrotherKS, Holmes C, Carpenter CL, Navidi WC et al. Envtl. Health Sciences N&l. Inw.. P. 0. Box 12233, Research Triangle Park, NC 27709. Cancer Res 1995;55:6035-7.

The possible association between lung cancer and a polymorphism of the CYP 1A I gene specific to African-Americans was examined using peripheral blood DNA from 144 incident cases of lung cancer and 230 population controls with detailed data on smoking and other risk factors for the disease. The CYPIAI variant allele was present in 15.2% of controls and 16.7 W of cases. The smoking-adjusted odds ratio for the presence of the variant allele in relation to lung cancer risk overall.was 1.3 (95% confidenceinterval, 0.7-2.4). According to histological type, the strongest association was observed for squamous cell carcinoma (odds ratio, 2.1). but this result was compatible with chance (95% confidence interval, 0.8-5.9). Adenocarcinoma was not materially associated with the presence of the variant allele (odds ratio, 1.3; 95 46 confidence interval, 0.5-3.2). No important associations were observed upon stratification by several risk factors for lung cancer, including smoking history, occupational exposures to asbestos and motor vehicle exhaust, or low intake of the micronutrient antioxidants R-carotene, vitamin E, or vitamin C. These results do not confirm an earlier report that this CYPIAI polymorphism may be an important risk factor for adenocarcinoma of the lung in African-Americans.

Transgenic mice bearing the polyomavirus large T antigen directed by 2.1 kb of the Keratin 19 promoter develop bronchiolar papillary tumors with progression to lung adenocarcinomas Lebel M, Webster M, Muller WJ, Royal A, GauthierJ, Mes-Masson A- M. Louis-CharlesSimardResenrch Center. CancerInstituteofMontreal. 1560 Sherbrooke Street East, Montreal, Que. H2L 4Ml. Cell Growth Differ 1995;6:1591-600.

Kemtin 19 is an intermediate filament protein produced by cells of simple epitheliaand basal cells of stratified epitheliaof different organs. These cell types are associated with important human cancers. We have used the kemtin 19 promoter to target the expressionof the polyomavirus (Py) large T-antigen, an immortalizing oncogene known to bind to the tumor suppressor retinoblastoma gene product, to epithelial cells. Individuals of the tmnsgenic mouse line Kl9PyLT-6 developed one or two nodules in one of their lungs. By histology, the nodules were papillary tumors that consisted of nonciliated epithelial cells of the terminal bronchioles. Inaddition, infiltratesemanating from thenodules were consistent with the development of pulmonary adenocarcinomas. In situ hybridization techniques demonstrated large T-antigen expression

in the tumors. Primary cultures were established from a lung tumor dissected from a Kl9PyLT-6 transgenic mouse. These large T- antigen- expressing cell lines produced the keratin proteins reminiscent of the epithelial origin of the lung tumor. However, further molecular studies indicated that these cell lines did not express Clam cells or pneumocytes markers. S.C. injection of the cell lines into nontmnsgenic syngeneic mice produced tumors in 2 weeks that resembled malignant pulmonary adenocarcinomas. These animals, which display tumor progression in situ, and the cell lines derived thereof provide a useful system for the study of lung tumorigenesis.

Tea consumption and lung cancer risk: A casecontrol study in Okinawa, Japan Ohno Y, Wakai K, Genka K, Ohmine K, Kawamura T, Tamakoshi A et al. Depanment of Preventive Medicine, Nagoya University School of Medicine. 65 Tsurumai-rho. Showa-ku, Nagoya 466. JQII J Cancer Res 1995;86: 1027-34.

To disclose the relationship between tea consumption and lung cancer risk, we analyzed the data from a case control study conducted in Okinawa, Japan from 1988 to 199 1. The analysis, based on 333 cases and 666 age-, sex- and residence-matched controls, provided the following major findings. (a) The greater the intake of Okinawan tea (a partially fermented tea), the smaller the risk, particularly in women. For females, the odds ratios (and 95 % confidence intervals) for those who consumed l-4, 5-9, and 10 cups or more of Okinawan tea every day, relative to non-daily tea drinkers, were 0.77 (0.28-2.13), 0.77 (0.26- 2.25) and 0.38 (0.12-1.18), respectively (trend: P = 0.032). The corresponding odds ratios for males were0.85 (0.46-1.55), 0.85 (0.46- 1.56) and 0.57 (0.31-1.06) (trend: P = 0.053). (b) The risk reduction by Okinawa” tea consumption was detected mainly in squamous cell carcinoma. Daily tea consumption significantly decreased the risk of squamous cell carcinoma in males and females, the odds ratios being 0.50 (95% confidence interval 0.27-0.93) and 0.08 (0.01-0.68). respectively. Thesefindingssuggestaprotectiveeffectofteaconsumption against lung cancer in humans.

Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors Kim Y-H, Dohi DF, Gil Ro Han Zou C-P, Oridate N, Walsh GL. Nesbitt JC et al. Department of fioracic. M. D. Anderson Cancer Center. Box 80, 1515 Holcombe Boulevard, Housron, TX 77030. Cancer Res 199.5;55:5603-IO.

Retinoids have demonstrated activity in the prevention of second primary tumors in patients with non-small cell lung cancer (NSCLC). They also contribute to the normal growth and differentiation of human bronchial epithebal (HBE) cells. Because retinoids mediate their actions through retinoid nuclear receptors (RARsand RXRs), aberrant signaling