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VII The Combined Effects of Radon Daughters and Cigarette Smoking
Pages 504-563

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From page 504...
... PART 1. Epidemiological Studies of Smoking and Radiation STUDIES AMONG SWEDISH METAL MINERS Studies of iron-ore miners in Northern Sweden reveal an excess of lung cancer that is related primarily to underground employment and exposure to radon.~7~28 In order to clarify the role of raxlon exposure combined with tobacco use on the occurrence of lung cancer, D amber and Larssoni° carried out a case-control study in a three-county area of Northern Sweden, in which cases were ascertained in the years 1972-1977.
From page 505...
... Pipe smoking was considered equivalent to cigarette smoking. Although pipe smoking has been related to lung-cancer risk, the affect of this assumption is difficult to assess since information on the percentage of pipe smokers and their inhalation patterns was not provided.
From page 508...
... 508 Cal it: C)
From page 509...
... son ~ .~ :^ ~ to :.
From page 510...
... Smoking status was not determined for nonminers. Among miners, smoking appeared to be protective for lung cancer, although the 90%0 confidence interval was large (relative risk, 0.49; 90%0 confidence interval, 0.1-2.2~.
From page 511...
... Public Health Service cohort of uranium miners of the Colorado Plateau have evaluated in detail the roles of radiation and cigarette smoking in the production of lung cancerS.~.22.24,32,3e The earliest report, by Archer et al.,, included 39 cases of lung cancer that arose in a well-defined, physically examined special study group during a 4-yr observation period (1964-1967~. Compared to lung-cancer rates among white male residents of mountain states, 1.1 and 4.4/10,000 personyr for nonsmokers and smokers, respectively, the rates among uranium miners were 7.1 and 42.2/10,000, respectively.
From page 512...
... VVhittemore and McMillan38 found substantial support for the multiplicative model, finding that it fit nearly as well as the saturated one. The authors rejected the additive model, which agrees with a preliminary analysis reported by Hornung and Samuels.~5 Further analyses found little improvement when smoking rate was added to the model, although this improvement might have been expected since pack-years incorporate cigarettes smoked per day and the subjects were matched by age.
From page 513...
... Variables of interest were age, cumulative WLM, and pack-yea". Because of case definition, this is a study of the determinants of moderate cell atypia or worse, and not of lung cancer.
From page 514...
... STUDIES AMONG NEW MEXICO URANIUM MINERS In the second part of this appendix, an evaluation is presented of the associations of cigarette smoking and duration of underground employment in a uranium mine with lung cancer in case-control data extracted from a cohort of New Mexico uranium miners. The results (Table VII-1)
From page 515...
... logistic regressions, which included years of smoking and years underground as continuous variables. Although the parameter estimates for the smoking effect were very similar for the miner group and for the controls not exposed to radon (thus suggesting a multiplicative interaction)
From page 516...
... Among nonsmokers, relative risks by the three categories of housing type were 1.0, 1.3, and 4.4, respectively, while among smokers risks were 2.7, 2.6, and 9.3. Although the data were sparse, a greater than additive interaction is suggested (Table VII-1.
From page 517...
... Although sample size was small and detailed evaluation was missing, this suggests an additive model for the two effects. Blot et al.6 have presented preliminary results of a second case-control study of 582 lung cancers identified during the years 1971-1980 from members of the Life-Span Study cohort.
From page 518...
... PART 2. The Committee's Analyses of Smoking and Radiation In this portion of the appendix, we present the results of this committee's analyses of data from three populations, which address the combined effect of radiation exposure and cigarette consumption on the risk of lung cancer.
From page 519...
... Analogous to methodology described in Annex 2A, we fit Poisson regression models to the data on smoking and exposure to radiation described below. We assumed that the expected number of events in each cell of a cross-classification is the product of the person-years accrued times the lung-cancer disease rate, which is modeled as an age- and calendar-periodspecific rate among nonexposed persons times a relative risk function, namely: person—yr x Ha x RR, (VII-7)
From page 520...
... For assessment of the combined effects of cigarette smoking and uranium-mining exposure, a case-control study was conducted within this cohort. The cases included all Hispanic and non-Hispanic white males diagnosed with lung cancer, regardless of whether cause of death had been coded as lung cancer.
From page 521...
... . CAS~CONTROL STUDY FROM THE LIFESPAN STUDY COHORT, JAPANESE ATOMIC-BOMB SURVIVORS The committee's current analysis of radon-exposed miners has revealed substantial differences in the effects of radiation on lung cancer in miners in comparison with the Japanese atomic-bomb survivors.
From page 522...
... bRelative risks from multiplicative model, Equation VII-1. new analysis of radiation exposure and cigarette use on lung-cancer risk, using data from a recent case-control study among atomic-bomb survivors, to formally evaluate their combined effects.
From page 523...
... A more appropriate examination of Table VII-5 ~ provided by comparing the RRs with fitted estimates Mom additive and multiplicative main effects models, respectively: TABLE VII-4 Data on Smoking Rate and Radiation Exposure from a Case Control Study of Lung Cancer among Japanese A-Bomb Survivorsa Radiation Exposure (red)
From page 524...
... Prentice et al.26 suggest that either multiplicative or additive relativerisk models fit the atomic-bomb survivor data for lung cancer, with little
From page 525...
... Years of Smoking < 10 10-99 100+ RRa RRb Males 0 1 1.0 8.8 1 1 1-34 1.8 2.0 1.2 1.6 1.1 35-44 1.6 4.9 9.6 2.0 1.9 45+ 18.4 13.3 87.2 14.0 11.3 RRa 1 1.4 5.5 RRb 1 1.0 3.4 Females 0 1 0.6 4.6 1 1 1-34 0.9 1.2 8.5 1.0 1.1 35-44 14.9 2.6 0.0 5.6 7.3 45+ 5.8 2.9 7.2 4.5 4.4 RRa 1 0.7 4.8 RRb 1 0.6 4.1 aRelative risks from additive model, Equation VII-2. bRelative risks from multiplicative model, Equation VII-1.
From page 527...
... Table VII-9 shows the number of observed lung cancers, person-years, and crude disease rate by WLM exposure and cigarette use when data were collapsed across age and year categories. The numbers differ slightly from the tables in Annex 2A because of a different cross-classification.
From page 528...
... bBaseline rate per 100,000 computed using expected number of cases, based on U.S. white male mortality rates for lung cancer adjusted to nonsmokers.
From page 529...
... As seen in Annex 2A, the effects of cumulative WLM decline with age at risk. Table VII-10 shows predicted relative risks by age group based on various models (risks relative to the lung-cancer rate in the entire cohort)
From page 530...
... and Cigarettes per day (n) ; Risks Relative to Rate in Entire Cohort No.
From page 531...
... Exposures for shorter periods of time are also of interest since exposure to elevated levels of radon may occur and end at any age. Tables VII-12 to VII-14 and Tables VII-15 to VII-17 provide for male smokers and nonsmokers, respectively, the ratio of the lifetime risk of lung-cancer mortality due to exposure occurring within stated intervals of age.
From page 532...
... vs 1 44.6 (37) Age effects for WLM 4(b)
From page 533...
... RADON DAUGHTERS AND CIGARETTE SMOKING TABLE VII-12 Ratio of Lifetime Risks (Re/Ro) by Age Started and Age Exposure Ends for Various Rates of Annual Exposurea for Male Smokers b 533 Age (yr)
From page 534...
... and a multiplicative interaction between smoking and exposure to radon progeny. bRo, the calculated lifetime risk for unexposed male smokers, is 0.123.
From page 535...
... RADON DAUGHTERS AND CIGARETTE SMOKING TABLE VII-13 Lifetime Risk (Re) by Age Started and Age Exposure Ends for Various Rates of Annual Exposurea for Male Smokers 535 Age (yr)
From page 536...
... and a multiplicative interaction between smoking and exposure to radon progeny. Note that Re includes Ro, the calculated lifetime risk for unexposed male smokers, 0.123.
From page 537...
... RADON DAUGHTERS AND CIGARETTE SMOKING TABLE VII-14 Years of Life Lost, (Lo—Le) by Age Started and Age Exposure Ends for Various Rates of Annual Exposurea for Male Smokers b 537 Age (yr)
From page 538...
... and a multiplicative interaction between smoking and exposure to radon progeny. Lo, the calculated lifetime risk for unexposed male smokers, is 69.0 yr.
From page 539...
... RADONDAUGHTERSANDCIGARETTESMOKING TABLE VII-15 Ratio of Lifetime Risks (Re/Ro) by Age Started and Age Exposure Ends for Various Rates of Annual Exposurea for Male Nonsmokersb 539 Age (yr)
From page 540...
... bRo, the calculated lifetime risk for unexposed male nonsmokers, is 0.0112.
From page 541...
... RADON DAUGHTERS AND CIGARETTE SMOKING TABLE VII-16 Lifetime Risk (Re) by Age Started and Age Exposure Ends for Various Rates of Annual Exposurea for Male Nonsmokers 541 A e ( r)
From page 542...
... and a multiplicative interaction between smoking and exposure to radon progeny. Note that R e includes R 0, the calculated lifetime for unexposed male nonsmokers, 0.0112.
From page 543...
... RADON DAUGHTERS AND CIGA~TTE SMOKING TABLE VII-17 Years of Life Lost, (Lo—Le) by Age Started and Age Exposure Ends for Various Rates of Annual Exposurea for Male Nonsmokersb 543 Age (yr)
From page 544...
... 0 0.28 0.56 0.83 1.13 1.44 1.64 1.70 1.71 1.71 10 0.28 0.56 0.87 1.18 1.38 1.44 1.46 1.46 20 0.29 0.60 0.91 1.12 1.18 1.20 1.20 30 0.31 0.64 0.84 0.91 0.93 0.93 40 0.33 0.54 0.61 0.63 0.62 50 0.22 0.29 0.30 0.30 60 0.07 0.09 0.09 a estimated with the committee9s TSE model (Chapter 2) and a multiplicative interaction between smoking and exposure to radon progeny.
From page 545...
... RADON DAUGHTERS AND CIGARETTE SMOKING TABLE VII-18 Ratio of Lifetime Risks (Re/Ro) by Age Started and Age Exposure Ends for Various Rates of Annual Exposurea for Female Smokersb 545 Age (yr)
From page 546...
... and a multiplicative interaction between smoking and exposure to radon progeny. bRo, the calculated lifetime risk for unexposed female smokers, is 0.0582.
From page 547...
... RADON DAUGHTERS AND CIGARETTE SMOKING TABLE VII-19 Lifetime Risk (Re) by Age Started and Age Exposure Ends for Various Rates of Annual Exposurea for Female Smokers 547 Age (yr)
From page 548...
... and a multiplicative interaction between smoking and exposure to radon progeny. Note that Re includes Ro, the calculated lifetime risk for unexposed female smokers, 0.0582.
From page 549...
... RADON DAUGHTERS AND CIGARETTE SMOKING TABLE VII-20 Years of Life Lost (Lo—Le) by Age Started and Age Exposure Ends for Various Rates of Annual Exposurea for Female Smokers b 549 Age (yr)
From page 550...
... and a multiplicative interaction between smoking and exposure to radon progeny. bLo, the calculated lifetime for unexposed female smokers, is 75.9 yr.
From page 551...
... RADON DAUGHTERS AND CIGARETTE SMOKING TABLE VII-21 Ratio of Lifetime Risk (Re/Ro) by Age Started and Age Exposure Ends for Various Rates of Annual Exposurea for Female Nonsmokers b Age (yr)
From page 552...
... bRo, the calculated lifetime risk for unexposed female nonsmokers, is 0.00602. 2.660 4.301 2.660 Exposure Rate = 20.00 (WLM/yr)
From page 553...
... RADON DAUGHTERS AND CIGARETTE SMOKING TABLE VII-22 Lifetime Risk (Re) by Age Started and Age Exposure Ends for Various Rates of Annual Exposure a for Female Nonsmokers Age (yr)
From page 554...
... and a multiplicative interaction between smoking and exposure to radon progeny. Note that Re includes Ro, the calculated lifetime risk for unexposed female nonsmokers, 0.00602.
From page 555...
... 0 0.00 0.00 0.00 0.00 0.01 0.01 0.01 0.01 0.01 10 0.00 0.00 0.00 0.00 0.00 0.01 0.01 0.01 20 0.OO 0.OO 0.OO 0.OO 0.OO COO 0 DO 30 0.00 0.00 0.00 0.00 0.00 0.00 40 0.00 0.00 0.00 0.00 0.00 50 0.00 0.00 0.00 0.00 60 0.OO 0.OO COO Exposure Rate = 0.20 (WLM/yr) 0 0.00 0.00 0.01 0.01 0.01 0.01 0.01 0.01 0.01 10 0.00 0.00 0.01 0.01 0.01 0.01 0.01 0.01 20 0.00 0.00 0.01 0.01 0.01 0.01 0.01 30 0.00 0.00 0.01 0.01 0.01 0.01 40 0.00 0.00 0.00 0.00 0.00 50 0.00 0.00 0.00 0.00 60 0.OO COO COO Exposure Rate = 0.50 (WLM/yr)
From page 556...
... and a multiplicative interaction between smoking and exposure to radon progeny. bR<,, the calculated lifetime risk for unexposed female nonsm`,kers,; is 76.7 yr.
From page 557...
... TABLE VII-24 Histologic and Physiologic Changes in the Respiratory Tract, Other than Malignancy, Associated with Cigarette Smoking36 Large airways Small airways Lung parenchyma Mucous gland hypertrophy and hyperplasia Dysplasia and metaplasia of epithelial cells Increased epithelial permeability Impaired mucociliary transport Inflammation Goblet cell metaplasia Epithelial cell metaplasia Increased mucus production Inflammation Fibrosis Increased cell numbers Altered cell populations Altered function of some cells Emphysema
From page 558...
... Nevertheless, the eBect of radon daughters in the presence of smoking must be interpreted in the context of the changes in lung structure and function, which can be readily demonstrated in many smokers.36 In this regard, several pulmonary disease processes resulting from cigarette smoking have been associated with increased lung-cancer risk: chronic bronchitis and chronic obstructive pulmonary disease. By epidemiological convention, chronic bronchitis refers to chronic sputum production.
From page 559...
... The finding of increased lung cancer in persons with underlying respiratory disease and mucus hypersecretion conflicts with the hypothesis that increased mucus production reduces penetration of alpha particles into the tracheobronchial epithelium and thus protects against cellular damage.3 THE ASSOCIATION BETWEEN LUNG CANCER, SMOKING, AND RADIATION Exposure to radon progeny and cigarette consumption are each associated with lung cancer in a complex way. Because there are only a few studies on the combined effects of radiation exposure and tobacco smoke, the amount of information for their interaction is limited.
From page 560...
... exposure; the effect on interactions of tobacco use before and after radiation · the role of cigarette use on the histological distribution of radiationassociated lung cancer; · the relationship of smoking to other measures of radiation expm sure, for example, working-level rate, cumulative WLM, and duration of exposure; and · the role of other agents associated with lung diseases, such as asbestos, silica, and arsenic.
From page 561...
... 1981. Survivorship models for lung cancer mortality in uranium miners is cumulative dose an appropriate measure of exposure?
From page 562...
... 1979. An exposuretime-response model for lung cancer mortality in uranium miners effects of radiation exposure, age and cigarette smoking.
From page 563...
... 1983. Lung cancer mortality among U.S.


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