223

59

224

"SE OF URINARY COTININE IN ASSESSING RISK FOR EXWSURE TO ENVIRONMENTAL TOBACCO SMOKE (ETS) IN CANINE LLING CANCER. J. Reif, K. Lower, G. Ogilvie. Colorado State University, Fort Collins, CO USA.

We recently demonstrateda" association (OR-1.6) between exposure to ETS and risk for canine lung c~cer in a case-control study (Am J Epidemiol 135:234,1992). The purpose of this study was to determine whether urine cotinine could be used as a biomarker to assess exposure to ETS among dogs. Subjects were eelected from among outpatients at a veterinary teaching hospital. Urinary cotininef creatinine ratios were measured by radio- immunoassay. The wan ratio in 58 dogs living in homes with smokers was 18.6 and that in 56 dogs living in homes without smokers was 2.2 "g/mg (p< 0.001). Urinary cotinine was related to the number of smokers in the home in a dose-dependent manner. Cotinine concentrations were 10.0, 17.8 and 55.0 rig/rug in homes with one, two and three or more smokers. A similar relationship was observed for number of cigarettes amoked. The relationship between cotinine and prevalence Of respiratory and other symptoms was assessed. This study adds further support to the use of dogs a8 animal sentinels for lung cancer induction by environmental tobacco smoke.

225

EVALUATION OF K-RAS MUTATIONS IN SPUTUM SAMPLES BY SINGLE- STRANDED CONFORMATION POLYMORPIUSM (SSCP). K. Kelly, M.D., Univ. of Colorado, Denver, co.

Currently there is no screening test available to detect lung cmcer at an early, curable stage. Studies performed twenty years ago examining chest radiograph with or without sputum cytology were insensitive. Today, with the sophisticated tools of molecular biology, reexamination of screening for lung cancer is warranted. lluough DNA technology it is evident that carcinogenesis requires multiple genetic alterations. An early genetic event which has been observed in several epithelial cancers is a mutation in the K-ras ““cogax. A single point mutation in codon 12 of K-ras has been demons!rated in 304/o (45 /280) of surgically resected lung tumor specimens with non-small cell histology. No aberration has been found in patients in a small subset with small cell carci~~cm~a.

To determine if K-ras plays a role in lung carcinogenesis which could be manipulated to create a screening test for lung cancer, sputum from patients with lung tumors and sputum from patients with varying degrees of atypia have been examined for point mutations in codon 12 of K-ras by SSCP. SSCP is a sensitive method for detecting single base differences in polymerase chain reaction (PCR) products. It also allows for direct DNA sequencing to he performed and thus eliminates the time consuming procedures of cloning the PCR product into a vector system, isolating the vector, and then performing DNA sequencing. Twenty- seven samples have been PCR amplified for the fust 100 base pairs of the K-ras gene. During amplification 1 ul of a P12 dCTP was added to the reaction mixture. A” aliquot of the product was then heat denatured and electrophoresed through a 6% nondenaturing acrylamide gel. The gel was dried and placed on the Phosphorlmager screen. The screen was developed 3 hours later. Controls included DNA exlmcted from white blood cells and the lung adenocarcinoma cell line A549. Abnormalities have been observed in 1X27 samples, 806 patients with known tumors and 4/l I with atypia. DNA sequencing is underway to identify tbe genetic alteration which is accounting for this abnormality. Sequencing of normal PCR products gives the expected results. It will also be important to perform a comparative analysis in patients with available tumor DNA and this is currently underway. SSCP is a simple but sensitive procedure which can be technically performed on DNA isolated from sputa. Further investigation utilizing SSCP as a potential screening test for lung cancer is warranted and can be piloted with other potential genetic markers.

AN OPERATRD CASE OF BILATRRAL BRQNCHIOLO- ALVEOLAR CAltCIlUOMA, SHOWING FAMILIAL AGGREGATION OF LUNG CANCER HiroharuTSLJJI,M.D.,ShinsukeHARA,M.D.,Yutaka TAGAWA,M.D., Kattnmobu KAWAHARA,M.D., Hiroyoshi AYABE,M.D., MasaoTGMITA,M.D. The First Dcpaamcnt of Surgery, Nagasaki University School of Medicine, Nagasaki, Japan

An operated case of bilateral bronchioloalveolar carcinoma on 56-

year-old female was reported. She was pointed out right abnormal

shadow on chest rentogenogram by mass survey in June 1992. Sputum

cytology revealed class V, adenocarcinoma Mass shadow in both lower

lobes were found out by chest computed tomography. Simultaneous

bilateral thoracotomy was performed by submammary transvers skin

incision in the level of fourth intercostal space. Right lower lobcctomy

and left S9 partial resection were undergone. Bronchioloalveolar

carcinomawas confirmed by microscopic findings in both specimens.

Four members of seven sibilings had lung cancer and one of

them had renal cell carcinomasimuhaneously. Furthermore her father,

two of maternal uncles, one cousin and one nephew also had lung cancer.

Two brothers and a nephew of lung cancer were confiied well

differentiated adenocarcinoma by pathological examhmtion

226

A IWORT ABOUT SMOKING HAMIS OF flXLl.AN HEALM m Arvlrl C.‘. Per&i P., Rstone M , Barbieti A.‘. Rnbbl8ti S. , Wwdori P.S. Masironi R.S. Santi L. _ *Italian League against Cancer.Cenoa: ” National Institute for Canrer Researrh, Anna: ‘Dept. of Medkinc. Horpl~al of Ala. ‘Trenc: S Health Service USI. Id. 6npdl (FI): S EMASH. Qnewi. Physicians. nurses and other health workers play a fundamental role in smoking prevention as non smnldng exemplars IO the general pnpulatbn. If health workers smoke, mast publk be&h mesaages aimed at the prcrcotion of smoking would loose impact. The ltnll~n League agahwt Cancer in rollabnration with the lnnlttne for Cancer Rereuch In Genoa has been carrying nut a survey on the smoking rater. attttudes and belkfs of a repmntatlve sample of hospital ha&h workem, dactnrs and muss, from varluur titles in Raly. The survey was car&d nut by distributhy a self adminlnred open-ended multiple choice aaonlmow queuiommira to he&b pr&ssionals. The results repnrtad bale r&r mcatly to tha swkbl!J habits tn relation 10 sex, aa, edwatiatd level, profeasknwl quWk&nns and working areas of health pe- I from eeveml RatIan b-t& the response l-ate was over 70% 5642 quwWm&avarwmmd,oatdwbkh 1601 were from hos@tair in the city of Gmm, 377 from hospitals In cp3pou. a city near Florence, 1970 from Trem and 497 from Mpaiaa, 272 from Apulia region. 562 from Cagliari and 366 from Paksmo. The resuhs hawed marked differences of smoking prevalence antoe-t be&b prorculonalr working in clinical care area. Tlw parcen~ of smokers anwmg doctors concerninr their sex. ate: in Gznna 37% ol m&es and 3a of feaaiw in Palermo 36% and 42% In En&i 33% and 25% In Caglinri 34% and 379& In Trent 30% and 22% in Anulia reaion 31% and 39%~ in Mantua 28% and 21% Similar trend are ob6erved a&me nttrsex The &rrentagas of snwkers. concering their sex. are: in Genoa 44% of males and 38% of famaks: in Paletmo 57% e 311%; in Einpolr 37% of both sexes; in Cagliari 34% and 38% in Trent 37% and 33% in Apulia IX&XI 54% and 3% in Mantua 32% and 33%. Another vex important aspect assess& in this study, was to establish whether smoking doctors systematically adivlse their patlents a@“st smoking or not. The data obtained show tbac few doctors wba are smnkera advise their patients against sntoki~ (I. c in Gmna 4396, In Mantua 3OW. vlrh respect to the “on smoking physlrlans (87.51 and 70% respecthwly). Thesa consistent findings undcrllne the need to improve smoking prevention progrvns which should inv&c par~lrtduly do&s, in order 6 provide them sufficient knowledac to help rnmkina patients stopplna their