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Body ma.w index and lung cancer risk Kabat GC. Wynder EL. Division of Epidemiology, American Health Foundation, 320 East 43rd Street, New York, NY 10017. Am J Epidemiol 1992;135:769-74.

The relation of body mass index, based on self-reported weight 5 years prior to diagnosis, to lung cancer wss investigated in 3,607 lung cancer cases and 9,681 controls interviewed in B hospital-based csse- control study in eight US cities bewee” 1981 and 1990. Separate analyseswerecarriedout by smokingstatussnd by sex. At&adjustment for covariates, odds ratios for lung csncer by levels of body mass index, taking 28 ss the referent, showed sn increasing linear trend with decreasing body mass index for current smokers and ex-smokers of both sexes and for female never smokers. These results are consistent with findings of B number of prospective studies. Further studies sre needed to determine whether the association of low body mass and lung cancer is due to factors associated with leanness or to s biologic effect of leanness itself.

Lung canw in a galvanizer an occupational disease? T&big G. Imtitut/Polik Arbeits-/Sozialmed., HospitaLFrraFse I, 6900 Heidelberg. Arbeitsmed Sozialmed Praventivmed 1992;27:243-6.

The case of a 52-year-old nonsmoker is reported, who developed lung cancer. Post mortem analyses of lung tissue demonstrate high chromium concentrations. This is regarded as B result of s 30-year period of exposure to chromium VI compounds ss sn electroplater. According to criteria of the legal system of occupational diseases in Germany, it wss concluded that the causal relationship between exposure to carcinogenic chromates and squamous cell carcinoma of the lung is probable. The importance of lung tissue analyses is discussed, with respect to long latency periods in chemical carcinogenesis.

Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells from lung cancer patients: No correlation with adduct levels in lung Van Schwten FJ, Hillebrand MJX, Van Leeuwen FE, Van Zandwijk N, Jansen HM, Den Engelse L et al. Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CXAmsterdam. Csrcinogenesis 1992;13:987-93.

Smokers of cigarettes sre exposed to a number of carcinogens, including polycylic aromatic hydrocarbons (PAHs), and sre at B high risk for lung cancer. PAHs exert their carcinogenic activity after metabolic activation lo reactive intermediates that can damage DNA through adduct formation. Measuring DNA adducts in peripheral white blood cells (WBC) could serve ss B means of monitoring human exposure to genotoxic agents and subsequently risk assessment. In this study, DNA from WBC obtained from 39 lung csncer patients was examined for PAH-DNA adducts both in an ELISA using a polyclonal antibody against benm(a]pyrene 7,8diol-9,10-epoxide (BPDE)-DNA and the 32P-past-labeling technique. The ELISA results showed BPDE- DNA antigenicity in WBC DNA from 12/38 (32%) patients and adduct levels ranged from 1.5 lo > 150 adducts in IO* nucleotides. The autoradiographs of chromstograms of ‘2P-post-lab&d digests of WBC DNA from the 38 patients showed B variety of adduct spots; relative adduct labeling (RAL) values ranged from 0.3 to 407 adducts in IO* nucleotides. In 18 of the 38 (47 96) persons an adduct spot was detected that co-chromstogrsphed with the major BPDE-DNA adduct (BPDE- dG); RAL values ranged from 0.03 to 382 adducts in IO* nucleotides. Correlations were not significant between the adduct levels in WBC and smoking habits, age or sex. From 20 patients of the ssme group lung tissue was collected at surgery and examined for PAH-DNA adducts by ELISA and ‘*P-post-labeling assay. No significant correlation was found between DNA adduct levels in blood and lung. This finding stresses thelimitstionsoftheuseofWBCssasurrogateforadduct levels in the target organ.

Lung cancer detection and prevention: Evidence for an interaction between smoking and genetic predisposition SellersTA, PotterJD, Bailey-WilsonJE, Rich%% RothschildH, Elston RC. Division of Epidemiology, I-210 Moos Tower, 515 Delaware St. S.E., Minneapolis, MN 55455. Cancer Res 1992;52:Suppl. 2694s-7s.

The initiation and promotion of cancer is thought to result from B series of genetic mutations, some of which may be inherited. Our analysis of 337 lung cancer families suggested that, after allowing for anindividusl’spack-yearsoftobaccouse, thepattemofdiseasewssbest explained by Mendelian codominant inheritance of an allele that produced earlier sge of onset. Since lung cancer rarely occurs in the absenceofexposure to tobacco, differences in theprevalenceofsnmking across generations could have a profound influence on the tit of genetic models. In the present study, families were partitioned into two groups, based on the birth cohort of the proband, i.e., born before World War I (age at death, 60 years) or born after World War I (age a( death, < 60 years). Thispartitionwsschosenbecause the year 1915signaled thestart of the dramatic rise in tobacco use in the United States. In younger proband families, in whichpamntswere morelikely to smoke, Mendelian codominsnt inheritance provided the best tit to the data. In older proband families, for whom smoking among parents was less prevalent, the ‘no major gene’ and ‘environmental’ hypotheses were rejected; however, no Mendelisn models could be distinguished. If the results on the families with the most homogeneous exposure to tobacco scross generations (born after World War I) reflect the true underlying biology, then the influence of genetic factors in the psthogenesis of lung has been underestimated; the cumulative probability pf lung cancer at age 80 for s noncarrier of the gene, at the average level of tobacco consumption, is close to mm, implying that virtually all lung cancer occurs among gene carriers. Identificatmn of this putative genetic factor has profound implications for the detection and prevention of lung cancer.

New potential chemopreventive agents for lung carcinogen&s of tobacco- specific nitrosamine Chung F-L, Morse MA, Eklind KI. American Health Foundation, I Dana Rood, Valhalla, NY10595. Cancer Res 1992;52:Suppl. 2719s. 22s.

Cigarette smoking is the major cause of lung cancer in humans. The continuous increase in the prevalence of cigarette smoking worldwide demands a practical means to circumvent this serious health problem. Our research has focused on the development of new chemopreventive agents against lung carcinogenicity of the tobacco-specific nitrosamine 4-(metbylnitrosamino)-l- (3-pyridyl)-1-butsnone. Several aromatic isothiccyanates have been identified as effective inhibitors of 4- (methylnitrosamino)-I-(3-pyridyl)-l-butanone- induced lung tumorigenesis. Phenethyl isothiocysnate, a natural constituent of crucifemus vegetables, protects F344 rats and A/J mice from 4- (methylnitrosamino)-l-(3-pyridyl)-l-butanone-induced lung tumorigenesis. The alkyl chain length in the aromatic isothiocyanates is an important structural feature for the inhibitory potency. The inhibitory efficacy increases as the alkyl chain elongates up to 6 carbon atoms. Thus, 6-phenylhexyl isothiocysnate is approximately 50 to 100 times more potent than phenethyl isothiocysnate. The remarkable efficiency of 6-phenylhexyl isothiocyanate suggests its potential as s chemopreventiveagent in intervention trials. The tissuedistribution and excretion of phenethyl isothiocyanate were studied in mice. Two major urinary metsbolites were identified as the mercaptopyruvic acid and the N-acetylcysteine conjugates. A urinary marker was developed to quantitate the uptake of phenethyl isothiocyanate in humans after consumptionofwatercmss,acrucifemusvegetablerichingluconashlrtiin, the glucosinolate precursor of phenethyl isothiocysnate. Considering the anticarcinogenic activity of phenethyl isothiocysnate, this marker may eventually be useful in assessing the role of dietary phenethyl isothiocysnate uptake in lung cancer risk.