Health Effects of Exposure to Radon BEIR VI (1999) / Chapter Skim
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Appendix C Tobacco-Smoking and Its Interaction with Radon
Appendix C Tobacco-Smoking and Its Interaction with Radon
Pages 224-253
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From page 224... ...
For former smokers, risk declines with the duration of smoking cessation (USDHHS 1990~. The pattern of inhalation of the tobacco smoke and the types of cigarettes smoked have a lesser influence on the risk of smoking (Wu-Williams and Samet 1994~.
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From page 225... ...
Incom plete understanding of the combined effect of these two carcinogens remains a key uncertainty in assessing the risk of indoor radon, and the consequences of synergism between radon and smoking in making quantitative risk estimates have not been universally appreciated. The underground miners who were participants in the epidemiologic studies that are the basis for currently used risk estimates were primarily smokers, and epidemiologic data from the miners' studies have not provided a precise characterization of the lung-cancer risk arising from radon exposure in never-smokers.
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From page 226... ...
Exposure-Dose Relationships · Differing patterns of physical activity and ventilation for smokers and nonsmokers · Exposures of smokers and nonsmokers differ in activity-size distributions · Differing patterns of lung deposition and clearance in smokers and nonsmokers · Differing morphometry of target cells in smokers and nonsmokers Carcinogenesis · Alpha particles and tobacco smoke carcinogens act at the same or different steps in a multistage carcinogenic process smoking. At most, the information on smoking in the studies provides some indication of elements of the smoking history, such as number of cigarettes smoked and age of starting to smoke; at a minimum, there is information on whether the participants had ever been regular cigarette smokers.
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From page 227... ...
In the absolute risk model, the effect of exposure on disease risk, ~x, does not depend on the level of rO. The selection of the risk model, absolute or relative, thus has substantial implications for interpreting the combined effects of two agents and additionally for extending risks observed in one population to another population which may not have comparable rO because of differing patterns of risk factors other than the exposure of interest.
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From page 228... ...
Current analytic approaches compare the combined effect to predictions based on either additivity or multiplicativity of the individual effects. A factor may be an effect modifier under additivity and not an effect modifier under multiplicativity.
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From page 229... ...
Imprecision may also limit estimates obtained from such modeling approaches. Implications for Interpreting Risk Estimates These general considerations underscore the complexity of characterizing the joint effects of smoking and radon-progeny exposure using epidemiologic data, whether from cohort studies of uranium miners or case-control studies in the general population.
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From page 230... ...
In the above formula, the attributable risk figure for smoking includes those cases caused by smoking alone and radon and smoking acting together; similarly, the attributable risk figure for radon includes those cases caused by radon alone and radon acting together with smoking. Combining the attributable risk estimates for smoking and radon counts the jointly determined cases twice.
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From page 231... ...
. LUNG CANCER IN THE GENERAL POPULATION Trends of Lung-Cancer Occurrence Over the Century For the United States, vital statistics document lung-cancer deaths from the late 1930s (Table C-3)
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From page 232... ...
Proponents of this viewpoint argue that lung cancer would have been a more prominent cause of death before the presently dominant impact of cigarette-smoking, if the risks of indoor radon were in reality as high as estimated in currently applied risk models. Rates earlier in the century, particularly for women, have also been cited as indicative of the maximum number of lung-cancer cases that indoor radon might have caused, assuming that other causes of lung cancer had little impact (Yalow 1995~.
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From page 233... ...
Doll and Peto (1981) have argued that cancer mortality rates in persons under age 65 years of age are the most valid indicator of trends of cancer occurrence in
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From page 234... ...
Analyses of data from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute indicate increasing histologic diagnoses of lung cancer in the elderly across the decades of the 1970s and 1980s and less reliance in making the diagnosis on a clinical basis alone (Gilliland and Samet 1994)
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From page 235... ...
TOBACCO-SMOKING AND ITS INTERACTION WITH RADON 235 So ~ get It !
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From page 236... ...
Thus, lacking information on the determinants of background lung-cancer mortality rates earlier in the century, the rates can be interpreted only on the implausible assumption that there were no risk factors for lung cancer other than radon. Lung-Cancer Rates in Never-Smokers Only limited information on lung-cancer occurrence in never-smokers is available as calculation of either incidence or mortality rates requires an estimate of the population of never-smokers at risk for lung cancer during some time interval (the denominator of a rate)
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From page 237... ...
237 Cq o a' o no ·_4 C)
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From page 238... ...
The populations in both of these studies, numbering about one million in each, were enrolled by American Cancer Society volunteers who identified the participants, obtained information on smoking and other risk factors for cancer, and periodically determined the vital status of the enrollees (USDHHS 1996~. Participants in the first study, now referred to as Cancer Prevention Study I (CPS I)
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From page 239... ...
Cigarette-smoking increases the risk for each of the principal histologic types of lung cancer: squamous cell carcinoma, small cell carcinoma, adenocarcinoma, and large cell carcinoma (Wu-Williams and Samet 1994~. A synergistic pattern of effect modification between radon and cigarette-smoking implies that the already high risks of lung cancer in cigarette smokers are augmented more than additively by the additional risk imposed by exposure to indoor radon.
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From page 240... ...
240 ~CPS-II Smoker CPS-I Smoker tCPS-II NS CPS-I NS APPENDIX C 1,300 1,200 1,100 1,000 900 800 700 600 500 400 300 200 100 0 ~ 30 ~ \ , . ~ A ~\ 45- 50- 55- 60- 65- 70- 75- 80- 85+ ATTAINED AGE (Years)
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From page 241... ...
reviewed the animal studies that included exposure to both radon progeny and cigarette smoke. The relevant studies included the experiments involving rats conducted by the Compagnie Generate des Matieres Nucleaires (COGEMA)
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From page 242... ...
) M 605 1.3 1950 Various Wynder and others United States; 1953-55 F 47 57.4 1956 Various Haenszel and others United States; 1955-57 F 157 48.4 1958 Various Wynder and others United States; 1966-69 M 270 3.3 1970 Various Stayner and Weyman United States; 1969-71 M 420 13.8 1983 Various Samet and others New Mexico 1980-82 M 356 2.5 1988 F 232 8.6 Wu and others 1985 Los Angeles 1981-82 F 220 14.1 Schoenberg and others New Jersey 1982-83 F 994 10.0 1989 Ives and others 1988 Houston 1977-80 F 259 4.6 COGEMA experiments showed synergism if the exposure to cigarette smoke followed the exposure to radon progeny; synergism was not found if the smoke exposure preceded the radon-progeny exposure.
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From page 243... ...
bWLM, working-level-month. In spite of long-term research by two groups of investigators, the animal experiments on smoking and radon progeny do not supply strong evidence on the combined effects of the two exposures.
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From page 244... ...
The analytic approach for assessing the combined effect of radon and smoking has also varied among the studies. Sample size limits interpretation of all of the studies and none of the individual studies have the number TABLE C-10 Case-control studies of the combined effect of smoking and radon Total Cases/ Study Total Never Reference Location/Years Smoking Cases Findings Axelson and others, Sweden/1960-81 177 Increased risk for non 1998 15 and occasional smokers vs.
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From page 245... ...
The report of the BEIR IV committee comprehensively reviewed the information on the combined effect of smoking and radon progeny in appendix VII. Since the publication of this report, the findings of several individual studies have been published that provide information on the combined effect of smoking and radon exposures; the study populations include Ontario uranium miners (Finkelstein and Kusiak 1995; L'Abbe and others 1991)
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From page 246... ...
246 o .5 Coo.
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From page 247... ...
TABLE C-12 Analyses of the combined effect of smoking and radon progeny exposure in six studies of underground minersa revalue Mixture Study Multiplicative Additive ~p-valueb Chinese tin miners 0.02 0.08 -0.3 0.39 Colorado uranium miners 0.58 0.04 0.7 0.49 Newfoundland fluorospan miners 0.53 0.67 -0.1 0.85 New Mexico uranium miners 0.15 0.11 0.4 0.16 Radium Hill uranium minersC Swedish iron miners 0.43 0.31 0.3 0.38 aBased on Tables 17a, 18a, 19a, 20a, and 21a in Lubin and others, 1994a. bRefers to fit of mixture model versus full model.
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From page 248... ...
TABLE C-13 Lung-cancer mortality rates and relative risks by cumulative WLM using data from all cohorts on 2,620 workers who never smoked Cumulative WLM <100 100-399 400-799 800-1599 1600 Total Cases 6112513964 Person-years 29,14212,1934,8162,9671,37550,493 Mean WLM 22.0213.5556.01,1532,332248.5 Rate x 1000 0.20.95.24.46.51.3 RRa 1.002.0810.910.823.8 95% CI 0.7 - 6.33.5 - 33.93.3 - 35.86.6 - 86.2 aRRs adjusted for cohort, previous occupational exposure, and attained age. Overall (ERR/WLM)
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From page 249... ...
The excess relative risk was greatest for small cell carcinoma but the heterogeneity of radiation risk among the three histologic types was not statistically significant. Other recent investigations of lung cancer in the atomic-bomb survivors have addressed histologic patterns of lung cancer (Land and others 1993)
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From page 250... ...
showed that the pattern of combined effects was consistent with additivity of the excess relative risks. This study is limited by the small number of lung-cancer cases and by the potential modifying effects of chemotherapy.
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From page 251... ...
Previous Risk Models As discussed above, in using a model to estimate the numbers of radonattributable lung-cancer cases, an assumption is needed as to the pattern of combined effects of smoking and radon. In most, but not all, risk assessments, a multiplicative pattern of interaction between smoking and indoor radon has been assumed.
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From page 252... ...
In the extreme circumstance of the aerosol generated at the time of active smoking, the projected exposure-dose coefficient was only half that under normal conditions. There has not yet been formal epidemiologic investigation of the combined effect of passive smoking and radon and statistical power for assessing the joint effect would be anticipated to be extremely limited.
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From page 253... ...
Mortality rates from lung cancer earlier in this century and rates in never-smokers offer at most a biologically inappropriate upper bound for the numbers of lung cancers attributable to radon progeny absent cigarette-smoking.
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