Lung Cuncer. 7 (I 991) 261-278 Elsewer

261

ABSTRACTS

Prevention

Use of “time windows” to investigate lung cancer latency intervals at an Ontario steel plant Finkelstein MM. Heolrh Studies Service. Onfario Mimstry of Lobour.

400 Universiry Avenue, 8rh Floor, Ibronto, Onr., M7A 177. Am J Ind Med 1991;19:229-35.

This paper describes an apphcation of the time wmdows method to an examination of the temporal pattern of lung cancer risk among steel workers. Case-control methodology was utilized. The cases were 36 men who had died of lung cancer and the controls were 289 men who had died of any other cause. The number of years ol employment in the steel pouringareawasusedasasurrogatemeasureofexposure. Thedata wereexaminedbycontingency tableanalysisandbylogistic regression, which permitted adjustment for exposures in multiple time windows and the use of continuous, rather than categorical, measures of expo- sure. II was found that lung cancer risk was associated with exposures occurring between 18 and 30 years before death. It cannot yet be determined whether this time course reflects a biological response or the temporal pattern of exposure to an as yet unidentified toxic agent.

Screening for lung cancer. A critique of the Mayo Lung Project Fontana RS, Sandcrson DR. Woolner LB, Taylor WF, Miller WE, Muhm JR et al. Division of Thoracic Diseases and internal Medrcme,

DeparrmentofDiagnoslic Radiology. MayoClinic. ZWFirslSlreer SW,

Rochester, MN55905. Cancer 1991;67:Suppl 1155-64. The National Cancer Institute of the United States recently sponsored

three large-scale. randomized controlled trials of screening for early lung cancer. The trials were conducted at the Johns Hopkins Medical Institutions, the Memorial Sloan Kettering Cancer Center, and the Mayo Clinic. Participants were middle-aged and older men who were chronic heavycigarettesmokcrsand thusathighriskofdevelopinghmg cancer. Screening procedures were chest radiography and sputum cytology, the only screening tests of established value for detecting early stage, asymptomatic lung cancer. In the Hopkins and Memorial trials the study population was offered yearly chest radiography plus sputum cytology every 4 months, The control population was offered yearly chest radiography only. In these trials the addition of sputum cytology appeared to confer no lung cancer mortality rate advantage. The Mayo Clinic trial compared offering chest radiography and sputum cylologyevery4 monthstoofferingadvice that the twotestsbeobtained once a year. This trial demonstrated stgnificantly increased lung cancer detection, resectability,and survivorship in the group offered screening every 4 months compared with the control group. However, there was no significant ditTcrence in lung cancer mortality rate between the two groups. The statistical power of these trials was somewhat limited. Nevcrthclcss, results do not justify rccommendmg large-scale radiol- ogic or cytologic screening for early lung cancer at this time.

Epidemiology and etiology

hIcreased risk of lung cancer in the melting department of a second Ontario steel manufacturer Finkelstein MM, Boulard M, Wilk N. Health Sudies Service, Ontario

Ministry of Labour, 400 University Avenue. 8th Floor. Toronto, Ont.,

M7A 1T7. Am J Ind Med 1991;19:183-94. A study of lung cancer among workers at an electric arc steel making

operation was performed to follow up on the observation of a lung cancer cluster in the melt shop of another plant. The study group comprised 335 deceased men identified from plant records. Eight of thirty men who had ever worked in the pouring pit area died of lung cancer(PMR 276; p < 0.01). but increased risk was not found elsewhere in the melting department. There was a significant trend in lung cancer risk with the length of employment tn the pit area during a time window 18-30 years before death. Smoking data suggested that smoking alone could not account for the increased risk. An industrial hygiene assess-

ment found present exposures to carcinogenic metals and sihca to be within current guidelines. No polycyclic aromatic hydrocarbons were detected. This is the second steel plant for which we have found increased lung cancer risk in the pouring areas. The causative factors have not yet been identified.

Crystalline silica and lung cancer: A review of recent experimental evidence Holland LM. He&h, Safely and Environment Division, Los Alamos

National Laboratory. MS K499, Box 1663, Los Alamos. NM 87545.

Regul Toxicol Pharmacol 1990;12:224-37. The International Agency for Research in Cancer (IARC) has re-

cently staled that crystalline sihca should be regarded as a potential carcinogen. The IARC bases this statement on a Ending that there is limited evidence of carcinogenicity in humans and sufficient evidence for carcinogenicity in animals. Recent laboratory animal experiments demonstrating a carcinogenic response to silica exposure have intensi- lied scienttfic and regulatory concern lor crystalline silica as a respira- tory carcinogen. Studiesof human populations have been contradictory in demonstrating a causal relationship between crystalline silica expo sure and lung cancer. This paper reviews recent experimental evidence and attempts to identify the gaps and inconsistencies in our understand- ing of the relationship between exposure to crystalline sdrca and the 1~0 diseases of concern: silicosis and pulmonary neoplasia. Given our current level of understanding and the need for more sctenliftc data it seemspremature to initiatechanges in cxposureregulationsatthislime.

Potential lung cancer risk from indoor radon exposure Harley NH, Harley IH. Institute of Environmental Medicme. New York

University Medical Center. New York, NY. CA Cancer J Chn 1990$0%5- 75.

The contribution of radon daughter exposure to excess lung cancer in underground mtners is universally accepted. These mmers received exposures from tens to thousands of WLM in a relatively few years. Although the miners were also exposed to other noxious agents in mines, the appearance of the excess lung cancer mortality in several types of mines and the mcrease with increasing exposure provtde convincing evidence of the role of radon as the carcinogen. It IS conceivable that exposures to radon at an average concentration of one to two pCi/Iiler. the levels for a majority of homes, might not produce cxccss lung cancers. This would require that a lifettme exposure at low concentrations produce a different response from that of a few years al higher levels for the miners. This is unlikely but not impossible. The current environmental epidemiology is of varying quality. The better studies may give some answers in a few years. These studies are more likely to establish an upper limit of risk than to provide an exposure- response model. Present risk estimates cannot be used accurately in es- ttmating the overall lung cancer rtsk to the US population, since there are no good data on average exposure and exposure distribution. For example, the number of homes above the EPA gutdeline of four pCi/ liter may range from two million to IOmillion. Anestimateof theactual radon exposure in the US may be forthcoming from a planned EPA survey. But these data will not be available for a few years. In the conservative tradition of radiation protection, indoor radon exposures in homes are estimated to produce a number of excess lung cancers m the population. One estimate by the NCRP’ is about 10,OCQ deaths per year in the US, for an average annual estimated exposure of 0.2 WLM (about one pCi/Iiter). The National Academy of Sciences (BEIR IV)” estimates 13,tXkl deaths for the same exposure, and the EPA’s estimate is 5,ooo to 20, ooo.

Specific Ki-rascodon61 mutations may determine thedevelopment of urethan-induced mouse lung adenomas or adenocarcinomas Nuzum EO. Malkinson AM, Beer DC. Deparmtent of Pharmacology,

Toxicology and Therapeutics, University of Kansas Medical Center.

39th and Rambow Boulevard. Kansas City. KS 66103. Mol Carclnog

1990:3:287-95.

In A/J strain mice, the carcinogen urethan induces lung adenomas and adenwarcinomas that contain Ki-ras-activating mutations primar- ily in codon 61. These mutationsaffect the middleadenine in codon 61

262

resulting in the substitution of either arginine (AT GC transition) or leucine (AT TA transversion) for the wild-type glutamine. To analyze the expression of the wild-type and mutant Ki-ras mRNAs in primary mouse lung tumors and transformed mouse lung cell lines, we utilized reverse transcription of total mRNA and DNA amplification by the polymerase chain reaction. The wild-type allele of codon 61 was expressed in all normal lung and primary tumor samples and in all transformed cell lines, except one. Significantly, the leucine-substi- tuted allele was expressed primarily in very small lung adenomas, whereas the arginine-substituted allele was expressed in large lung adenocarcinomas and transformed lung cell lines. The relative amounts of expression of the mutant versus wild-type Ki-ras alleles and the total Ki-ras mRNA expression was similar in both lung adenomas and adenocarcinomas. Further, the arginine mutant allele was present in ad-

These results sugges; that the specific ‘a&vating Ki-ras mu&n is more critical to either lung adenoma or adenocarcinoma development than is the tumor’scelloforigin or theextent to which die mutant alleles areexpressed. Adistinctroleofthespecific activating Ki-ras mutations in affecting lung tumor growth or malignant potential is indicated.

Cancer risk among glass factory workers: An excess of lung cancer? Saukila R, Karjalainen S. Pukkala E, Oksanen H, Hakulinen T, Teppo L et al. Finnish Cancer Registry, Liisankaalu 21 B, SF-001 70 Helsinki. Br J Ind Med 1990;47:815-8.

A total of 3749 workers employed for at least three months in two Finnish glass factories (cohorts A and B) were followed up for cancer in 1953-86throughtheFinnishCancerRegistry.IncohortA(l353 men, 1261 women), 106 primary cancers were diagnosed among men, and their standardised incidence ratio (SIR) for all cancers was 99. Among women the risk was low (65 cases, SIR 64). In cohort B (450 men, 685 women), the relative risk of cancer was close to unity for both men (57 cases) and women (75 cases). The risk of cancer was analysed by primary site, type of work, years since first exposure, and age at diagnosis. The only significantly increased risks were those of lung cancer among men (SIR 130, 95% CI 100-167, cohorts A and B combined).andskincanceramongglassbIowers(SIR625,95%CI 129- 1827). An increased risk of lung, stomach, and colon cancer as well as of brain tumours has been reported in previous studies. It is postulated that the excess risk of lung cancer, detected in this study, can also be accounted for by lifestyle, and not only by possible occupational exposures, because a similar excess risk of lung cancer has been found previously for all industrial workers in Finland. Although the risk of stomach cancer in this study was increased among glass blowers, it was not high in the largest groups of plain glass workers. The risks of lumours of the central nervous system and colon were not increased either.

Urban-rural differences in lung cancer occurrence. Time trends in Jews in Israel Rennert G, Epstein L. Department of Convnuni~y Heolrh. Cannel Hospiral. Hoifa 34362. Lung Cancer (The Netherlands) 1990;6: 159- 64.

An urban excess of lung cancer has been documented in several areas in the world. It was at least partially attributed to excess of smoking and occupational exposure. As lung cancer rates among Jews in Israel are. low, in face of moderately-high smoking prevalence, it was of interest to study the urban/rural ratio in this population. Two-thousand one- hundred and sixty cases diagnosed during three time-periods between 1962 and 1982 were studied. An urban-rural ratio of 1.3-1.5 in the various periods among males and 0.7-1.3 among females was demon- strated. These ratios, with the exception of that of 0.7 in females in the last period, are in accordance with former reports from countries with much higher lung cancer rates.

A compartment model of carcinogenesis in lung cancer Mixoue T, Ike& M, Ogimoto I, Yoshimura T. Deparrnenr of Clinical Epidemiology. Insriture oflnductrial Ecological Science, University of Occupational and bvironmenral Health. Kilakyushu 807. J UOEH 1990;12:403-IO.

A compartment of carcinogenesis which describes separately the process of smoking-related cancer and that of smoking-unrelated lung cancer is presented. This model is well lined to the equation represent- ing the lung cancer incidence rate of the British physicians’ cohort. The compartment model is shown to agree with the frozen type of incidence curve among en-smokers. This model is biologically plausible in the

policies in a community and for h&ddr educatibn tion smoking data, we calculated the change of risk after the cessation of smoking.

Influence of cigarette smoking on the levels of DNA adducts in human bronchial epithelium and white blood cells Phillips DH, Schoket B, Hewer A, Bailey E, Kostic S, Vincze I. Chester Beatry Lobororories, Innirure of Cancer Research. Fulham Road, Lon- don SW3 658. Int J Cancer 1990;46:569-75.

The presence of carcinogen-DNA adducts in human tissues is evi- denceofexposuretocarcinogensandmaybeanindicatorofcancerrisk. DNA was isolated from non-tumorous bronchial tissue of 37 cigarette smokers, 8 former smokers and 8 non-smokers and analyzed for the presence of aromatic and/or hydrophobic DNA adducts in the “P-post- labelling assay. Adducts were detected as bands of radioactive material when S-‘zP-labeIled deoxyribonucleoside 3’S’-bisphosphates were chromatographed on polyethyleneimine-cellulose tJc plates, and the patterns indicated the formation of adducts by a large number of compounds. Adduct levels detected in DNA from non-smokers, former smokers and current smokers were 3.45 f 1.62.3.93 f 1.92and 5.53 f 2.13 adducts/IOt nucleotides. respectively. The differences in adduct levels between smokers and former and non-smokers were statistically significan: l.p < 0.01); and among the smokers, signficanl correlations were found between adduct levels and both daily cigarette consumplion and total cigarette consumption (daily consumption x number of years smoked). DNA was also isolated from the peripheral-blood leukocytes of 31 heavy smokers (>20 cigarettes/day) and 20 non-smokers and analyzed by ‘2P-post-labe.lling. Adduct levels in the smokers’ samples were not significantly different from levels in the non-smokers’ samples (2.53 f 1.31 and 2.12 f 1.44 adducts/lO’ nucleotides, respectively). Thus, evidence for carcinogen exposure was found in human bronchial epithelium, a target tissue for tobacco-induced tumour formation, but not in peripheral-blood cells, indicating possible limitations in the use of the latter as a surrogate, non-target tissue source of DNA for monitoring human exposure to inhaled carcinogens.

Case-controlstudyofresidentialradonandlungcanceramongNew Jersey women Schoenberg JB, Klotx JB, Wilcox HB et al. Chronic Disease Epidemi- ology Program, New Jersey State Department of Health, CN369. Tren- ran. NJ 08625. Cancer Res 1990;50:6520-4.

To evaluate the association of indoor radon exposure with lung cancer risk, yearlong _ track detector measurements of radon were conducted indwellings which hadbeenoccupied foratleaw IOyearsby 433 New Jersey female lung cancer cases and 402 controls who were subjects in a larger population-based study. Adjusted odds ratios were 1.1 (90% confidence interval, 0.79-I .7). 1.3 (90% confidence interval, 0.62-2.9),and4.2(90%confidenceinterval,0.99-17.5)forexposuresof 1.0-1.9.2.0-3.9, and 4.0-I I.3 pCi/liter, respectively, relative to expo- sures of less than I .O pCiiliter, showing a significant trend (l-sided P = 0.04) with increasing radon concentration. The tread was strongest amonglightsmokers(lessthan 15cigarettes/day. I-sidedP=O.OI).The trend for lung cancer risk wirh estimated cumulative radon exposure was slightly weaker (l-sided P = 0.09). The increase in relative risk for each unit of cumulativeexposute, 3.4% (90% confidence interval O.O- 8.0%) per working level month, was consistent with the range of 0.5- 4.0% per working level month generally reported for underground miner studies, supporting the extrapolation of the occupational data to the residential setting. However, the possibility of selection biases, the small number of high exposures, andother uncertain necessitate caution in interpretation of these data.