58

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lung cancer among underground miners but the risk to general population remains controversial. Environmental surveys have found high concentration of radon in indoor air of Mexico City dwellings (Radiat Protec Dosimetry 34, 183.19901, building material (Nuclear Tracks, 12, 767.19661 and groundwater INucl Tracks radiat Meas, 19, 305,19911, so there is concern about the relation between radon daughters exposure and Lund cancer in Mexican population. In Mexico Lund cancer incidence is incraasing and becoming a public health problem, with increasing incidence in patients never smokers under 40 years old (Chest, 104, 1477.1993). There have been none study in our country of indoor radon and Lund cancer, so wa decided to begin looking for alpha activity in lung tissue as a marker of exposure to radon daughters in 30 autopsy casas with non- occupational exposure to radon, randomlv selected from the National Instituta of Respiratory Diseases.

Lung tissue l2g wat weight) was taken from the 5 lobes of each patient (10 woman mean age 64 and 19 males mean age 60; 10% and 74% ware smokers, raspectivelyl. Twenty samples by lung were analyzed. The technique for alpha-particle autoradiography described by Henshaw was used IPhys Mad Biol, 24, 1227.19791.

The pathology associated with the daath of patients was as follows: AIDS (3%). Lund cancer (6%). lung disease (pneumonia, pneumonitis, asthma, tuberculosis) 66% and cardiovascular disease 25%. The population exposed to wood smoke during all their lives ware 13%.

Alpha activity was found in 96% of the studied population. No significant differences were found in the number of alpha particles by lobe, however, there was a higher incidende of alpha particles in smokers. We could not assess passive smoking yet. The identification of high concentration of radon in indoor air and alpha particles in lung tissue of Qeneral population, allOWs to continue with more studies to evaluate the risk from radon daughters exposure associated to Lund cnacer in Mexican population, specially in people living in highly polluted areas like Mexico City and exposed to high indoor aereosol concentration generated by gas stoves, smoking and wood use. Rrrrrsh + by Th @wwnmw ti WInto .G&mK*pER/L Rqk 086.

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FEASIBILITY OF USE OF PLASMA AND URINE LEVELS OF GASTRIN RELEASING PEFTIDE AND INSULIN-LIKE GROWTH FACTOR I AS POTENTIAL PREDICTORS FOR RISK OF SECOND LUNG CANCER DEVELOPMENT AMONG PATIENTS WITH STAGE I OR 11 NON-SMALL CELL LUNG CANCER. M.J. Kelley, D. Holden, P.T. Le, G. Sladek, S. Steinberg, J. Mulshine, B.E. Johnson. National Cancer Institute and National Naval Medical Center; Bethesda, MD, USA

Prior attempts at early detection for lung cancer utilized chest radiographs and sputum cytology examination but have failed to decrease overall mortality in screened populations. Several neuroendocrine (NE) peptides have been found to be elevated in the serum and/or urine of patients (pts) with lung cancer as well as cigarette smokers without clinical evidence of lung cancer. We have initiated a clinical study to test the feasibility of serially measuring serum and urine NE peptide levels in patients with resected stage I or II non-small cell lung cancer (NSCLC), whose risk of development of a second lung cancer is about l-5% per year, as potential predictors of risk for lung cancer development. Plasma and urine levels of gastrin releasing peptlde (GBF’) and insulin-like growth factor I (IGF-I) were measured every 3 months ln 15 pts with resected stage I or II NXLC and once in 9 individuals who never smoked using RIA. Among the pts with NSCLC, there were 7 males, 8 females, median age 64 (range 50X3), 11 pts with stage I and 4 with stage II. The nonsmoking group was younger with median age 35 (range 29-53) with 6 males and 3 females. Total follow-up for pts with NSCLC is 13 pt-yrs. All plasma GRF’ levels were below the threshold of detection (78 pg/ml) for the assay used. Median urine GRF’ was 94 pg/mg creatinine (n=23; range 8.5 to 636) in pts with NSCLC and 27 (n=7; range ~2.1 to 307) in nonsmokers. Median plasma IGF-I level was 26 ng/ml (n=33; range 3 to 108) in pts with NSCLC and 42 (n=9; range 22 to 53) while mediin urine IGF-I level was 46 ng/mg creatinine (n=28; range 8.7 to 164) in pts with NSCLC and 47 (n=7; range 15 to 111) in nonsmokers. We conclude that 1) the GRP RIA used may not be sensitive enough to detect GRP plasma levels in this population; 2) GRP urine levels vary over 100 fold in both pts with NSCLC and nonsmokers, and these levels are higher in pts with NSCLC; 3) there is no significant difference in either IGF-I plasma or urine levels between pts with resected NSCLC and nonsmokers. Among the NE peptides described here, urine GRP levels are most promising in terms of detection of a wide range of values and a clear difference between pts with NSCLC and nonsmokers. Two additional NE proteins, calcitonin and chromogranin A, are also beiig measured in these pts.

RISK OF SRamn CAWCSM (SC) In LQWG-TERM SDRvIvOR.S or 81ALLCEIJ.LUUGCAWCXR mzLC). B.E. Johnson, N. Murray, E.G. Shaw, M.H. Huber, D.S. Ettinger, 1. Mabzy, R. Feld, F.A. Shepherd. S.C. Grant. D.H. Johnson, J. Aisner, P.A. Tucker for the Lung Cancer Working Cadre.

TO evaluate the risk of SC followinu SCLC. WB identified patiente surviving r2 years from 9 institutions. Data we=* available at the time of this analysie on 483 of 614 patients. The numbers of expected cancers were e&i-ted by cumulating person years of observation from 2 years after the diagnosis of ECLC to date of death, SC, or last follow-up, whichever occurred first, and then applying appropriate cancer incidence rates from the 8EBR program of the NCI. 63 SC occurred. comnaeed to 18.4 exnected. based on population rates (Obs&ved/Expec~.d [O/El 3.4; 95% confidence interval [CII 2.6-4.41. The risks of a SC were 2.9 (95% CI 2.0-4.1) during years 2-4; 3.6 (2.3-5.5) ya*r-e 5-9; and 6.1 (3.0-11.3) ,I0 years (p trend 0.05). Smoking related cancers were 6.9-fold increased (95% CI 5.1-9.1). 36 of the SC rere non emall cell lung CMCI)I (NSCLC) (O/E 11; 95% CI 7.6-15). The risks of NSCLC also increased over time: O/E 8 (95% CI 4.5-13) yee 2-4; O/E 11 (5.9-19) yrB 5-9, snd O/E 21 (8.5-44) (p for trend 0.03). Smoking status was available in the records of 456 patients. Risk of second NSCLC by smoking:

B Number 0 O/E (95% CI) Smokin Statu q EXC~BB Risk Nonsmoker (cig) 11 0 0 Quit before SCLC 119 9 9.6 (4.4-18) 24.5 Quit at dx SCLC 144 11 12 (5.9-21) 23.2 Continued smoking 152 15 16 (8.8-26) 31.6

The risk of NSCLC W(LB constant over time among those who had quit before the diagnosis of SCLC, but increased (Llllong those who quit at the time of dx (O/R 23 at lO+ years) or continued smoking (O/E 100 at lO+ years). These reeulte confirm our previous finding that continued Bmoking increases the risk of second NCSLC in this patient cohort.

222

Non-small Cell Lung Cancer and PAH-DNA Adducts as a Biomarta

Tang, DL’. Santella, R.M.‘, Mayer J.‘, Tsai, W-Y?, and Perera, F.P’. ‘Division of Environmental Sciences, *Division of Biostatirtiu, School of Public Health; Columbia Univenity NY NY

In a study of 136 non-small cell lung cancer patients and 115 controls at the Columbia-Presbyterian Medical Center (CPMC). Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were measured by ELBA in both leukocytes and lung tumor specimens collected prior to or at surgery. Information on smoking, diet and occupational exposure was collected. Adducts in leukocytes were signiticantly higher in casea (8.5 * 10.7. MeankSD) than in controls (4.1 2 4.2). the odds ratio was 5.3 (C.I. = 1.8-16.0. p<O.Ol). After adjusting for age, sex, ethnic&y. season and number of cigaretta smoked per day, adduct level, remained significantly higher in cased (peO.01). Adducts in leukocytes were significantly increased in smokers and u-smokers than in nonsmokers among ca.~~ and controls both separately and comb&d, with and without adjusting for age, seq ethnicity and season. Linear regression analysii showed a modeat but signiGcant increase in PAH-DNA adduct levels with heavier smoking in the 51 tacos who were current smokers (p=O.OS) but not in 22 current smoking cnntrols. A seasonal variation was observed in uu(r but not in controls. Adducts in leukocytea showed a correlation with adducta ‘in the lung tumor tissue (~0.34, P=O.OS) but not with adducta in nontumor tissue (r=-O.O4, ~~0.83). In this study PAH-DNA adducta in peripheral leukocytcr are associated with cigarette smoking and wiih PAH-DNA adducts in target lung tumor tissue.