Abstracts/Lung Cancer II (1994) 123-150

treatments. Research in lung cancer etiology has identified several biological markers that can be integrated into standard smoking treatments to motivate refractory smokers. The results of early studies that have supplemented brief interventions with personalized feedback from biological marker testing have been promising. This typeof motivational intervention might increase the 14% to 18% quit rates typical of brief interventions to quit rates more typical of multisession clinic treatments (25 96 to 35 96). The most effective smoking cessation interventions are likely to be those that combine feedback of exposure to tobacco (eg, CO levels) and physiological smoking outcomes (eg, abnormal cytological changes), with markers of individual susceptibility (eg, CYP2D6 metabolic phenotype/genotype). However, a note ofcaution is indicated when communicating information based on biological marker testing, particularly genetic information. Research in cancer screening and genetic screening has shown significant short-term increases in psychological distress in many persons who are informed about abnormal

results. However, it is important to note that screening for lung cancer susceptibility differs from cancer screening and traditional genetic screening (eg, Huntington’s chorea) in many important respects. Most importantly, individuals found to have an increased susceptibility to develop lung cancer have the potential to prevent the disease by altering their smoking behavior. Therefore, biological marker feedback must be provided in conjunction with concrete quitting advice and assistance to minimize serious emotional reactions. However, for some individuals, heightened perceptions of susceptibility to lung cancer may be a prerequisite for action. Numerous ethical issues also are raised by the application of biological marker testing to smoking treatment. For example, questions of access to genetic information by insurance carriers and employers and issues of genetic discrimination must be addressed. When providing biological, and especially genetic, information, it is critical that consent be fully informed, including information about the accuracy of the tests and their predictive value. Confidentiality is vitally important when performing biological marker testing, particularly if interventions are performed at the worksite or in association with an insurance company. A number of methodological recommendations also can be made to guide future research in this area. For example, extensive pilot testing of biological feedback messages will be necessary to assure that the information can be understood by participants, and that it is presented in a nonthreatening and reassuring manner. Inaddition, theimpactoftheseinterventionsmustbeevaluated, not only with reference to smoking behavior change (eg, quit rates), but also with respect to psychological outcomes(eg, anxiety anddepression). Greater attention should also be paid to theoretically relevant mediating variables, including perceptions of risk, stage of quitting, decisional balance, and self-efficacy. Also, variables that influence the efficacy of biobehavioral interventions should be identified. For example, so&demographic characteristics such as educational level are likely to influence how biological information is processed and acted on. This underscorestheimportanceofincludingsubjectsofdiversesocioeconomic backgrounds in these trials. In addition, individual differences in personality and coping styles have been shown to play an important role in emotional responses and behavior in stressful medical situations and should be evaluated as potential moderator variables in this context.

Epidemiology and etiology

Saturated fat intake and lung cancer risk among nonsmoking women in Missouri Alavanja MCR, Brown CC, Swanson C, Brownson RC. Division of Cancer Etiology. National Cancer Inrritute, 6130 Executive Blvd., Rockville, MD 20852. J Nat1 Cancer Inst 1993;85:1906-16,

Background: Although the vast majority of lung cancer cases in women are caused by smoking, 9 %-20 % of cases occur in nonsmokers. Previous epidemiologic research on the relationship between lung cancer and diet has shown that fruit and vegetable consumption may confer a protective effect against lung cancer, while a diet rich in cholesterol and fat may increase risk. Putpow: The purpose of this case- control study was to examine the effects of a broad range of die&try factors on the risk of lung cancer in a population of nonsmoking white women30-84yearsofage. Me&& Atelephone-administeredquestion- naire was used to determine and/or verify eligibility with regard to age, gender, race,andsmokingstatus. Inasecoodinterviewatthepolticipsnt’s home, a widely used food frequency questionnaire was filled out, and logistic regression was subsequently used to analyze the responses. We obtained dietary information on 429 case subjects who had a diagnosis of lung cancer reported to the Missouri Cancer Registry between June I, 1986, and June 1, 1991, and 1021 control subjects. Ifacaaesubject had died or was too ill to be interviewed, next-of-kin familiar with the woman’s diet were interviewed instead. Of the 429 woman with lung cancer, 211 (49%) had lung adenocarcinoma. Results: A strongly increasing trend in lung cancer risk was observed with increased saturated fat consumptionamong thesenonsmoking women; the relative riskwasmorethansixfoldgreaterforthehighestquintileofconsumption than for the lowest quintile. The effect of saturated fat was more pro- nounced for adenocarcinoma than for other cell types. Weekly servings of beans and peas were significantly related to decreased lung cancer risk, while citrus fruit and juice showed a twofold increase in risk; this trend was also significant. Conclusion: By focusing on nonsmoking womenwithhmgcancer, includiigalargenumbarwithadenocaminoma, we observed a clear association with saturated fat consumption that may have been masked in earlier studies of lung cnncer involving a high percentage of smokers.

Mortality from lung cancer in Ontario uranium miners Kusiak RA, Ritchie AC, Muller J, Springer J. Health and&f&y Studies Unit, Ontario Ministry of L&our, Toronto, Ont. Br J Ind Med 1993;50:920-8.

Mortality from lung cancer was greater in Ontario uranium miners than in the general male population of Ontario (observed = 152, expected = 67.6, standardized mortality ratio 225, 95% confidence interval 191-264). Part of the excess of lung cancer may be because the proportion of men who are smokers or have smoked is greater in uranium miners than in Ontario men. Smoking does not explain the whole excess. Mortality from lung cancer in Gntario uranium miners is clearly related to exposure to short lived radon progeny. The excess relative risk of lung cancer from the same degree of exposure to short lived radon progeny is greatest five to 14 years after exposure and less subsequently. It is greater in men under the age of 55 years and less in older men. Part of the excess of lung cancer mortality in Ontario uranium miners is probably also due to exposure to arsenic that occurred earlier in gold mines. In Ontario uranium miners, the lung cancer mortality from exposure to arsenic increasesas the intensity ofexposure to short lived radon progeny increases. This finding is consistent with the hypothesis that the risk of lung cancer from exposure to arsenic is enhanced by exposure to other carcinogens. In Ontario uranium miners, the proportion of lung cancers that are small cell carcinomas is greater than in the general population. The proportion of small cell carcinomas is especialy great five to 14 years after exposure to short lived radon progeny and in men who die from lung cancer at younger ages.

Quantitative importance of asbestos as a cause of lung cancer in a Swedish industrial city: A case-referent study Jarvholm B, L.arsson S, Hagberg S, Oiling S, Ryd W, Toren K.

126 Abstracts/Lung Cancer II (1994) 123-150

Department of Occupational Medicine, Sahlgrenska Hospital, St. Si&idsS 195, S-412 66 Goteborg. Eur Respir 1 1993;6:

cancers of the hilar type, but is considered to be effective in detecting 1271-5. hmg cancers of the peripheral type. Positive and careful effort should be

We wanted to assess the quantitative importance of asbestos as a continued for the detection of early lung cancers in workers. cause of lung cancer. In a case-referent study, the exposure to asbestos, tobacco smoke and some other occupational exposure were compared between 147 cases of lung cancer (100 men, 47 women), 111 hospital referents, and 109 population referents, all below the age of 75 yrs and living in mn industrial city. The attributable risk of lung cancer due to asbestos exposure was 16 46 in men (95 56 confidence interval l-3 1%). No woman had occupational exposure to asbestos. We conclude that in the mid 1980’s tobacco smoking was the major attributable risk, being 95 % for men and 78 96 for women, but that in men asbestos was an appreciable contributing factor in the general population of a Swedish industrial city.

Main drug- and carcinogen-metabolizing enzyme systems in human non-small cell lung cancer and peritumoral tissues Toussaint C, Albin N, Massand L, Gruaenwald D, Parise 0 Jr, Morixet Jet al. Institut Gustave-Roursy, Pavilion derecherche 2.94SOS Villejuif Cedex. Cancer Res 1993;53:4608-12.

A survey of primary lung cancer among N’IT workers in the Tokyo area. The incidence and mortality during the past 30 years and significance of radiologic screening Miyagawa H, Yamada R, Tamura S. Department of Respiratory Medicine, NIT Tokyo Health Administration Ctr., 3-S-S Toranomon. Minato-ku, Tokyo 105. Jpn J Industr Health 1993;35: 395-402.

An epidemiological study of primaty lung cancer was conducted on NTT workers in the Tokyo area (about 40,000 persons). During the past 3Oyears(1960-1989), 77cases(71 malesand6females)ofprimaryhmg cancerweredetected by routinemedicalexamination(radiologicscreening by radiophotography at their workplaces) or by clinical symptoms, of whom 59 (54 males and 5 females) were dead as of the end of December 199 1. Standardized incidence rate and standardized death rate of the males by the direct method (5-yr age groups from 20 to 59 yr of age, per 100,000 population) were 4.5 in the 1960’s, 9.9 in the 1970’s and 9.8 in the 1980’s, and 3.3 in the 1960’s. 7.9 in the 1970’s and 8.2 in the 1980’s, respectively, with increase being observed from the 1970’s. Standardized incidence ratio and standardized death ratio of the males by the indirect method (5-yr age groups from 30 to 59 yr of age) were 107 in the 1970’s, 86.8 in the 1980’s, and 53.8 in the 1960’s, 99.4 in the 1970’sand98.5inthe 1980’s, respectively. Nosignificantdifference couldbeobservedwhencompsredtothenationalaverage. Byhistological type, 44 cases of adenocarcinoma, 12 cases of squamous cell carcinoma, 8 cases of small cell carcinoma, 7 cases of large cell carcinoma and 6 cases of other or unclear types were detected. Excluding the 3 unclear cases, of the 77 cases, 54 cases were peripheral type and the remaining 20caseswerehiIartypeonmdiophotography. Periphemladeoocarcioma was the most common type. Clinical stage by TNM classification was contirmed in 50 cases, of whom 12 cases were stage I, 5 cases were stage II, 9 cases were stage IIIA, 8 cases were stage IIIB and 16 cases were stage IV. As for the means of detection, 41 cases were detected by routine medical examination (radiologic screening by radiophotography) and 36 cases were detected by clinical symptoms. The lung cancers of thehilar typecould be detected by clinical symptoms at ahigher rate than by radiologic screening, but those of the peripheral type were detected at a significantly higher rate by radiologic screening than by clinical symptoms. The 41 screened cases were detected at an earlier stage and showed abetter prognosis than the 36 clinical cases. The rate of operable cases (75.6% in screened cases vs. 30.6 % in clinical cases) and 1, 2, 3 and4-yrsurvival. rates(lyr88.61 vs.41.4%,2yr48.6%vs. 17.3%, 3 yr 37.1% vs. 13.81, and 4 yr 34.3% vs. 10.3%) were significantly higher in the screened cases than in the clinical cases. Though the 5-yr survival rate was not significantly different between the two groups, the survivalcurvecalcul&dbyKaplan-Meiermethodand testbygeneraiixed Wilcoxon method showed that the prognosis of the screened cases were better than that of the clinical cases. Routine medical examination by radiological screening at workplaces is not sufficient to detect lung

To better understand the importance of drug-metabolizing enzymes in carcinogenesis and anticancer drug sensitivity of human non-small cell lung cancer, we studied the main drug-metabolizing enzyme systems in both lung tumors and their corresponding nontumoral lung tissues in 12 patients. The following enzymes were assayed by Western blot analysis: cytochromes P-450 (lAllA2, 2Bl/B2, 2C8-10, 2E1, 3A4); epoxide hydrolase; and glutathione S-transferase isoenzymes (GSTa, -, and a). The activity of the following enzymes or cofactor were determined by spectrophotometric or fluorometric assays: glutathione S-transferase (GST); total glut&&one; UDP- glucurono- syltransferase; 8-glucuronidase; sulfotransferase; and sulfatase. Results showedthepresenceofcytochromeP-450 lAl/lA2 inbothtumoral and oootumoral tissues. P-450 lAlllA2 levels were 3-fold lower in tumors compared to corresponding nootumoral tissues (P < 0.05). None of the other probed cytochromes P-450 were detected in either tumoral or oontumoral lung tissues. For the glutathiooe system, no significant difference between tumoral and oontumoral tissues was observed (GST activity, glutathione content, GSTa, - , and a). A positive linear correlation was observed between GST activity and GST-a or GSTa. No significant difference was observed for the glucuronide and the sulfate pathways and their corresponding hydrolytic enzymes. Epoxide hydrolase was significantly decreased in tumors compared to oootumoral lung tissues (P < 0.05). In conclusion, these results showed differences between non-small cell lung tumors and nontumoral tissues for cytochrome P-450 lAl/lA2 and epoxide hydrolase. These differences between tumors and peritumoral tissues with regard to these drug- metabolizing enzymes could reflect differences occurring after malignant transformation and may play a role in drug sensitivity to anticancer drugs.

Occupational risk factors for lung cancer among nonsmoking women: A casecontrol study in Missouri (United States) Brownsoo RC, Alavanja MCR, Chang JC. Div. Chronic Disease Prevention, Health Promotion, Missouri Department of Health, 201 Business Loop 70 West, Columbia, MO 65203. Cancer Causes Control 1993;4:499-504.

Occupationally related risk of lung cancer among women and among nonsmokershasnot been widely studied. Amcendyconductedpopulation- based, case-control study in Missouri (United States) provided the opportunity to evaluate risk of lung cancer associated with several occupational factors. Incident cases (o = 429) were identified through the Missouri Cancer Registry for the period 1986 through 1991, and included 294 lifetime nonsmokers and 135 ex-smokers who had stopped at least 15 years prior to diagnosis or had smoked for less than one pack- year. Controls (o = 1,021) were selected through driver’s license and Medicare files. Risk was elevated among women exposed to asbestos (ever: odds ratio [OR] = 3.5,95 percent confidence interval [CI] = 1.2- 10.0; > 9 yrs: OR = 4.6, CI = 1.1-19.2) and pesticides (ever: OR = 2.4, CI = 1.1-5.6; > 17.5 yrs: OR = 2.4, CI = 0.8-7.0). Risk also was elevated among dry cleaning workers (ever: OR = 1.8, CI = 1. l- 3.0; > 1.125~~~ OR = 2.9, CI = 1.5-5.4). Occupational risksforlung cancer among women merit further study.