beta-carotene, retinol and lung cancer chemoprevention in former asbestos workers

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20 Passive Smoking and Lung Cancer Among - Japanese Women. 2 1 Akiba, S., Blot, W.J., Kato, H. i. Radi- ation Effects Research Foundation, Hiro- shima Japan 730. 2. National Cancer In- stitute, Bethesda, Md. 20205, U.S,A. A case-control study conducted in Hiroshima and Nagasaki which involved interviews of 428 cases and 957 controls revealed a 50% increased risk of lung cancer among nonsmoking women whose hus- bands smoked. The risks tended to in- crease with the amount smoked by the hus- band, being highest among women who wor- ked outside the home and whose husbands were heavy smokers, and to decrease with cessation of exposure. The findings pro- vide incentive for further evaluation of the relationship between passive smokinq and cancer among nonsmokers. Table 2. Odds ratios for lung cancer by smoking status of subject and spouse Sex of Subject Spouse subject Smoker Smoker Case Control OR a 90% CI a Male Nob No b 16 101 1.0 Yes 3 9 1.8 (0.5, 5.6) Yes No 190 388 3.4 (2.1. 5,5) Yes 51 S6 4.2 (2.4. 7,3) Female No b Nob 21 82 1.0c --- Yes 73 188 1.5 (i.0.2.5) Yes No S 14 2.2 (0.9.5,1) Yes 50 56 3.6 (2.1.6.1) a Odds ratio and 90% confidence interval from matched palr/trlplet logistic analysis b Individual reported to have never smoked cigarettes c Referent category Measurements of PasSive Smoking and Estimates of Risk for Lung Cancer Among NoniSmoking Chinese Females. 2 KOO ~ L.C., Ho , J.H-C, Fra~meni , J,, B~ot , W., Lubin, J., Stone-, B.J. University of Hong Kong, Hong Kong; National Cancer Institute, Bethesda, Md., U.S.A.) Passive smoking exposure among women who had never smoked was studied in a retrospective case-control study in Hong Kong. In interviews of 88 cases and 137 district controls, lifetime exposure to passive smoking was measured in several ways and analyzed by conditional logistic regression to determine if dose-response relationships were present. At the high- est doses, the risk values from I) total years of exposure and 2) number of ciga- rettes per day smoked by the husband re- sulted in 2-3 times higher relative risk values for lung cancer. However, when the mean hours of exposure per day, total cumulative hours of exposure, or total added amounts of cigarettes smoked per day by all the cohabitants in the home were calculated, increase~ the risk for passive smoking were not found. Such data combined with occupational histories likewise did not result in higher risk values for women exposed vs. not exposed. Further study is needed to determine reasons for the inconsistent results, which may offer clues to clarify the association between passive smoking and lung cancer reported in several areas of the world. Some Large-Scale Comparison Between Five Types of Tobacco Constunption and Mortality From Carcinoma of the Trachea, Bronchus, and Lung in Canada. Ayiomamitis, A., Badawi, I. Department of Preven- tive Medicine and Biostatistics, Faculty of Medi- cine, University of Toronto, Toronto, Canada M5S IA8. Lung cancer is the number of one cause of death in Canadian males aged 35-84 (for all five-year age groups) and the second or third leading cause of death in Canadian women aged 35-74 (for all five-year age groups). In order to assess the long- term mortality of this disease and its relation to tobacco consumption, the most significant and yet easily controllable risk factor for carcinoma of the lung, mortality figures for carcinoma of the trachea, bronchus;and lung, and consumption figu- res for five types of tobacco (cigarettes, cigars, chewing and smoking tobacco, snuff) were collected from the publications of Statistics Canada for the period 1921-1982. All mortality rates were stand- ardized to the 1971 Canadian population for age and sex using the direct method. Tobacco consump- tion was standardized using a refined method for computing "Smokers-at-Risk" (abstract submitted to present conference) and related to the age-stan- dardized mortality rates (ASMR) using (non-para- metric) correlational analysis. By far, the great- est association between mortality from carcinoma of the trachea, bronchus, and lung, and tobacco consumption was with cigarettes where a very signi- ficant relationship was observed (r(s) = 0.98, p 0.005) for both males and females. Snuff, found to be negatively associated with mortality, was of borderline significance (r(s) = -0.77, p=0.07) whereas consumption of chewing and smoking tobacco, and cigars, yielded poor correlations (r(s) = -0.25, p =0.59; r(s)=0.14, 0=0.79; r(s)=0.36, p=0.43; respectively). The recent popularity of anti-smok- ing compaigns should lead to significant reductions in morbidity and mortality from this disease. Beta-Carotene, Retinol and Lung Cancer Chemopreven- tion in Former Asbestos Workers. McLarty, J.W., Kummet, T.D., Riley, L.L. University of Texas Health Center at Tyler, Tyler, Texas, USA. A lung cancer chemoprevention study is being conducted with a high risk group of former asbestos workers. This randomized double blind clinical trial uses beta-carotene and retinol versus placebo for a three-year period. The incidence of lung cancer and changes in bronchial epithelium, as monitored by repeated sputum cytology, will be the end-points measured by this trial. Serum levels of beta-caro- tene, retinol and retinol binding protein will be

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Passive Smoking and Lung Cancer Among - Japanese Women. 2 1 Akiba, S., Blot, W.J., Kato, H. i. Radi- ation Effects Research Foundation, Hiro- shima Japan 730. 2. National Cancer In- stitute, Bethesda, Md. 20205, U.S,A.

A case-control study conducted in Hiroshima and Nagasaki which involved interviews of 428 cases and 957 controls revealed a 50% increased risk of lung cancer among nonsmoking women whose hus- bands smoked. The risks tended to in- crease with the amount smoked by the hus- band, being highest among women who wor- ked outside the home and whose husbands were heavy smokers, and to decrease with cessation of exposure. The findings pro- vide incentive for further evaluation of the relationship between passive smokinq and cancer among nonsmokers.

Table 2. Odds ratios for lung cancer by smoking status of subject and spouse

Sex of Subject Spouse subject Smoker Smoker Case Control OR a 90% CI a

Male No b No b 16 101 1.0 Yes 3 9 1.8 (0.5, 5.6)

Yes No 190 388 3.4 (2.1. 5,5) Yes 51 S6 4.2 (2.4. 7,3)

Female No b No b 21 82 1.0 c --- Yes 73 188 1.5 (i.0. 2.5)

Yes No S 14 2.2 (0.9. 5,1) Yes 50 56 3.6 (2.1. 6.1)

a Odds ratio and 90% confidence interval from matched palr/trlplet logistic analysis

b Individual reported to have never smoked cigarettes c Referent category

Measurements of PasSive Smoking and Estimates of Risk for Lung Cancer Among NoniSmoking Chinese Females. 2 KOO ~ L.C., Ho , J.H-C, Fra~meni , J,, B~ot , W., Lubin, J., Stone-, B.J.

University of Hong Kong, Hong Kong; National Cancer Institute, Bethesda,

Md., U.S.A.)

Passive smoking exposure among women who had never smoked was studied in a retrospective case-control study in Hong Kong. In interviews of 88 cases and 137 district controls, lifetime exposure to passive smoking was measured in several ways and analyzed by conditional logistic regression to determine if dose-response relationships were present. At the high- est doses, the risk values from I) total years of exposure and 2) number of ciga- rettes per day smoked by the husband re- sulted in 2-3 times higher relative risk values for lung cancer. However, when the mean hours of exposure per day, total cumulative hours of exposure, or total added amounts of cigarettes smoked per day by all the cohabitants in the home were calculated, increase~ the risk for

passive smoking were not found. Such data

combined with occupational histories likewise did

not result in higher risk values for women exposed vs. not exposed.

Further study is needed to determine reasons for the inconsistent results, which may offer clues to clarify the association between passive smoking and lung cancer reported in several areas of the world.

Some Large-Scale Comparison Between Five Types of Tobacco Constunption and Mortality From Carcinoma of the Trachea, Bronchus, and Lung in Canada.

Ayiomamitis, A., Badawi, I. Department of Preven- tive Medicine and Biostatistics, Faculty of Medi- cine, University of Toronto, Toronto, Canada M5S IA8.

Lung cancer is the number of one cause of death in Canadian males aged 35-84 (for all five-year

age groups) and the second or third leading cause of death in Canadian women aged 35-74 (for all five-year age groups). In order to assess the long- term mortality of this disease and its relation to tobacco consumption, the most significant and yet easily controllable risk factor for carcinoma of the lung, mortality figures for carcinoma of the trachea, bronchus;and lung, and consumption figu- res for five types of tobacco (cigarettes, cigars, chewing and smoking tobacco, snuff) were collected from the publications of Statistics Canada for the period 1921-1982. All mortality rates were stand- ardized to the 1971 Canadian population for age and sex using the direct method. Tobacco consump- tion was standardized using a refined method for computing "Smokers-at-Risk" (abstract submitted to present conference) and related to the age-stan- dardized mortality rates (ASMR) using (non-para- metric) correlational analysis. By far, the great- est association between mortality from carcinoma of the trachea, bronchus, and lung, and tobacco consumption was with cigarettes where a very signi- ficant relationship was observed (r(s) = 0.98, p 0.005) for both males and females. Snuff, found to be negatively associated with mortality, was of borderline significance (r(s) = -0.77, p=0.07)

whereas consumption of chewing and smoking tobacco, and cigars, yielded poor correlations (r(s) = -0.25, p =0.59; r(s)=0.14, 0=0.79; r(s)=0.36, p=0.43; respectively). The recent popularity of anti-smok-

ing compaigns should lead to significant reductions in morbidity and mortality from this disease.

B e t a - C a r o t e n e , R e t i n o l and Lung Cancer Chemopreven- t i o n in Former A s b e s t o s Workers . McLarty, J.W., Kummet, T.D., Riley, L.L. University of Texas Health Center at Tyler, Tyler, Texas, USA.

A lung cancer chemoprevention study is being conducted with a high risk group of former asbestos workers. This randomized double blind clinical trial uses beta-carotene and retinol versus placebo for a three-year period. The incidence of lung cancer and changes in bronchial epithelium, as monitored by repeated sputum cytology, will be the end-points measured by this trial. Serum levels of beta-caro- tene, retinol and retinol binding protein will be

2!

monitored throughout the trial~ An exten-

sive dietary questionnaire will also be used to assess nutritional status. The study is currently in its patient re- cruitment phase: the study design will be discussed and preliminary analysis of the recruitment and compliance will be presented.

Heat-Stable Alkaline Phosphatase as a Useful Marker in Cancer Prevention.

Kobayashi, T., Harumiy, S., Ohe, T. Asia Medical Center, Oomiya, Saitama 330, Japan.

Heat-stable alkaline phosphatase

(HS-AP) was previously not considered important in cancer diagnostics because of its low detection rate as a result of the low sensitivity of the usual enzyme assay or electrophoretic analysis. But our fluorometric analysis is 200-fold more sensitive than usual used with p-ni- trophenyl phosphate as a substrate. The detection rate is 95%, if we use 0.3 U/I as low detection limit of HS-AP. We ob- served HS-AP is a very useful tumor mar- ker only in the follow up of cancer pa- tients, but of cancer prevention because of its high non-organ specificity, and its fundamental roles in carcinogenesis, gene activation and modulation. Nineteen cancer patients, who have direct or indirect smoking before the onset of disease, quit- ted smoking and was treated by immuno- thermochemotherapy. All of them are in good course and HS-AP decreased to lower level. We selected ii patients, who had abnormal value of HS-AP and other tumor markers, over 400 in Brinksman Index, but who had not a definite morphological diagnosis of cancer. These patients were treated by preventive measures with Re- fresh therapy plus avoiding smoking. HS- AP activity decreased in all patients. So we conclude biochemically that micro- cancer became smaller by the preventive treatment. In the comparative group the average value of HS-AP increased with tumor growth correspondingly. We thus demonstrated by using HS-AP as a marker that this preventive treatment is an effective approach for the lung and other cancers.

Valuable T~or Marker, Heat-Stable Alka- line Phosphatase Assayed by Fluorometric Analysis to Detect the Risk of Lung Can- cer and Other Cancers by Cigarette Smo- king. Kobayashi, T., Harumiya, S., Ohe, T. Asia Medical Center, Oomiya, Saitama 330, Japan.

We measured heat-stable alkaline phos- phatase (HS-AP, EC3-1-1) in human serum

by a simple, sensitive enzymatic analysis

involving the fluorogenic substrate naph-

tol AS-MX phosphate .(moclified Maslow's method). We carried out mass screening (n=361) by combina- tion assay of tumor markers, HS-AP, CEA, ferritin

(FT), RNase, IAP, FT/Fe, Sialic acid and ALP iso- enzymes. We classified the screenees into 5 tumor stages from microcancer (precancerous) to clinical cancer according to the concept of natural histor~ of cancer. The progression of tumor stages correlate well with the HS-AP activity and the percentage of smokers. Measurable amounts of HS-AP were detected in most normal individuals. The mean for 106 nonsmo- kers was 3.8 (SD 3.7.) U/l; for 113 smokers it was 17.7 (SD 24.3) U/I. Activity of HS-AP in smokers was about 6-fold the upper normal limit for nonsmo- kers. These coincide with the male standard mor-

tality rate of lung cancer in smokers against non- smokers (4.43) in Japan. Nonsmokers and smokers with above 20 U/I of HS-AP activity were 1.0 and 26.5%, respectively. We may conclude that HS-AP is able to define a group at risk. We demonstrated the risk of lung cancer and other cancers by smoking from the HS-AP activity before the onset of cli- nical cancer, instead of standard mortality rate in epidemiological works.

Indoor Exposure to Radon from the Ground and Bronchial Cancer Among Women.

Svensson, C., Eklund, G. Unit for Cancer Epidemi- ology, Karolinska Institute, Stockholm, Sweden. Pershagen, G., National Institute of Environmen- tal Medicine, Stockholm, Sweden.

A case-referent study on the possible associati- on between radon emanating from the ground and bronchial cancer was performed among 292 female lung cancer cases and 584 matched population re- ferents who had lived at least 30 years in the city of Stockholm, Sweden. The cases were diagno- sed during the period 1972 to 1980 with oat-cell and other types of anaplastic pulmonary carcinoma. Indoor radon and radon daughter measurements were made in a 10% sample of the dwellings where cases and referents had lived. A relative risk of 2.2 (p=0.01) was found for lung cancer associated with living in dwellings close to ground in areas with an increased risk of radon emanation. Smoking ha- bits did not appear to be a major confounding fac- tor for thi~ association although a detailed eva- luation was not possible. The measurements showed significantly increased radon daughter concentra- tions in ground level dwellings within radon risk areas where lung cancer cases had lived, indica- ting that this exposure was of etiologic importan- ce.

In conclusion, the present study suggests that exposure to radon and radon daughters in dwellings is related to an increased risk of anaplastic bronchial carcinoma. The results are in accordan- ce with some earlier findings. Further studies are recommended to elucidate the role of indoor expo- sure to radon and radon daughters in the etiology of lung cancer among the general population, espe- cially with regard to dose-response relationship.

Cytologic Screening for Lung Cancer in a High Risk Group.

Kimose, H.H., Kjeldsen, N.J., Mouritzen, C. Uni-