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A. a.(1)(a) i) a)DocumentҲa1DocumentE+N xNDocument Style oN=(Nl4{!*NF *  ׃  2qea2DocumentE+N xNDocument Style oN=(Nl4{!*N*    a3DocumentE+N xNDocument Style oN=(Nl4{!*N0     a4DocumentE+N xNDocument Style oN=(Nl4{!*N   . a5DocumentE+N xNDocument Style oN=(Nl4{!*N  2Ke p p ca6DocumentE+N xNDocument Style oN=(Nl4{!*N  a7DocumentE+N xNDocument Style oN=(Nl4{!*N ` ` ` a8DocumentE+N xNDocument Style oN=(Nl4{!*N ` ` ` Tech Init"66oInitialize Technical Style{"*NxN3{$E  1 .1 .1 .1 .1 .1 .1 .1 Technical2 } -^ a1Technical+N xNTechnical Document StyleN=(Nl4{#*N 4!     a2Technical+N xNTechnical Document StyleN=(Nl4{#*N *    a3Technical+N xNTechnical Document StyleN=(Nl4{#*N'   a4Technical+N xNTechnical Document StyleN=(Nl4{#*N&   28 $  .  a5Technical+N xNTechnical Document StyleN=(Nl4{#*N&   . a6Technical+N xNTechnical Document StyleN=(Nl4{#*N&!"  . a7Technical+N xNTechnical Document StyleN=(Nl4{#*N&#$  . a8Technical+N xNTechnical Document StyleN=(Nl4{#*N&%&  . 2o4j 0Pleading{$66oHeader for numbered pleading paper*NxN3{$E'(   ,#&m P7&P# X  y*dddyy*dddy H\1 H\2 H\3 H\4 H\5 H\6 H\7 H\8 H\9 H10 H11 H12 H13 H14 H15 H16 H17 H18 H19 H20 H21 H22 H23 H24 H25 H26 H27 H28   Ӽa1Right Par+N xNRight-Aligned Paragraph NumbersNl4{B*N8)*@   a2Right Par+N xNRight-Aligned Paragraph NumbersNl4{B*NA+,@` `  ` ` ` a3Right Par+N xNRight-Aligned Paragraph NumbersNl4{B*NJ-.` ` @  ` `  2Na4Right Par+N xNRight-Aligned Paragraph NumbersNl4{B*NS/0` `  @  a5Right Par+N xNRight-Aligned Paragraph NumbersNl4{B*N\12` `  @hh# hhh a6Right Par+N xNRight-Aligned Paragraph NumbersNl4{B*Ne34` `  hh#@( hh# a7Right Par+N xNRight-Aligned Paragraph NumbersNl4{B*Nn56` `  hh#(@- ( 2 0a8Right Par+N xNRight-Aligned Paragraph NumbersNl4{B*Nw78` `  hh#(-@pp2 -ppp Њ&m P7&P) `(CG Times (Scalable)&&m P7&P) `(CG Times (Scalable)&`\  PQP)\  ` TmsRmn 10pt (F)`\  PQP)\  ` TmsRmn 10pt (F)`\  PQP)\  ` TmsRmn 10pt (F)`\  PQP)\  ` TmsRmn 10pt (F)`\  PQP)\  ` TmsRmn 10pt (F)`\  PQP)\  ` TmsRmn 10pt (F)`\  PQP)\  ` TmsRmn 10pt (F)23|m#`\  PQP# & APPENDIX C ă  LUNG CANCER MORTALITY RATES ATTRIBUTABLE TO SPOUSAL ETS IN INDIVIDUAL EPIDEMIOLOGIC STUDIES ă   S!#`\  PQP#p)CS \APPENDIX C. LUNG CANCER MORTALITY RATES ATTRIBUTABLE TO SPOUSAL ETS IN INDIVIDUAL EPIDEMIOLOGIC STUDIES ă Many of the epidemiologic studies on lung cancer and environmental tobacco smoke (ETS) were part of larger investigations that included eversmokers and neversmokers. For those studies, the lung cancer mortality rate (LCMR) for all causes, appropriate to the location and time period of the study, has been obtained from other sources. Those values and parameter estimates from the studies are used to partition the excess LCMR from all causes (i.e., the excess after allowance for baseline sources) into components attributable to eversmokers (from current and former smoking) and neversmokers (from exposure to spousal ETS) and to estimate the LCMR in the subpopulations of interestunexposed neversmokers (meaning not exposed to spousal smoking), exposed neversmokers (exposed to spousal smoking), and eversmokers ("exposed" is not used to mean exposure to nonspousal ETS, which applies to the whole target population). The method is explained in Sections 6.3.1 and 6.3.2.Lung cancer mortality rates for the caseaccrual periods of casecontrol studies are displayed in Table C1 Table 1  Table 1 =x(x(#`\  PQP# Table C1. Female lung cancer mortality from all causes in casecontrol studies1  ddH ] "$4444 ddH ] "$4444 .EEEEEEEUEEEEEEEU. (< f<Study < Location Case accrual Begin Average EndAccrual 10 yrs average2Accrual-20 yrs average2.  .AKIBJapan1971805.136.057.084.572.30..BROWUSA19798215.6817.2919.099.494.75..BUFFUSA19768013.9415.2917.207.864.38..CHANHK19767723.5923.5923.5919.05*..CORR3USA19798226.026.0 26.0 9.494.75..GAO4China198486*18.0*14.335.13..GARFUSA1971819.4513.5517.206.87*..GENG4China1983*27.8 *13.83*..HIRA5Japan1965814.465.707.084.01*..HUMB3USA19808417.7 17.7 *10.555.13..INOUJapan1973835.556.537.464.932.95..JANE3USA19828423.7 23.7 *9.065.42..KABA6USA1961804.6913.2017.206.614.16..KALA6Greece1987896.586.5866.586.755.836..KATA6Japan198487*7.466*4.662.26..KOOHK19818322.3422.6122.7519.82*..LAMT6HK19838622.7523.4623.6921.33*..LAMWHK19818422.3422.8823.6920.09*..LEEEng/Wal19798216.2817.1117.8912.608.1..PERS6Sweden1961803.715.097.563.956*..SHIM6Japan1982857.467.4667.465.654.28..SOBU6Japan1986887.467.4667.466.364.93..SVEN6Sweden1983857.727.7267.725.783.80..TRICGreece1978806.886.405.995.755.317..WUUSA19818217.2018.1519.0910.144.96..WUWI8China198587*11.6*9.22*  XR1Rates are per 100,000 per year, standardized to the 1950 world population age distribution. Data are drawn from Kurihara et al. (1989), and annual rates for 2year periods were averaged over the years cases were accrued for each study unless otherwise noted. Where part (or all) of the accrual period fell 1 or 2 years outside the years for which rates were available, rates from the nearest 2year period available were assumed to apply to the missing years. U.S. rates are for white females only. `x.(continued on the following page)=ڐx(x(#`\  PQP#XR2The accrual10 years average is the average for the time period of the same length as the accrual period but 10 years previous to it. Similarly, the accrual20 years value is for the time period 20 years previous to the accrual period. 3Data for accrual period from 197882 rates in IARC (1987b), standardized to 1950 world population from Kurihara et al. (1989). For Correa, weighted average of white and black rates; for Humble, weighted average of Hispanic and nonHispanic white rates. 4Accrual period data for GAO and GENG derived from IARC (1987b) by standardizing to same 1950 world population used by Kurihara et al. (1989). GAO rates are for 197882; GENG, 1981 82. For the accrual10 years value, GAO and GENG are 197375 rates standardized to the 1960 world population from China Map Press (1979). The GAO accrual20 years value is nonadjusted 1961 rate from Kaplan and Tsuchitani (1978). 5The nested casecontrol study of Hirayama (mortality rates for this study also apply to the cohort study in which it is nested). 6Where rates for the period were not available in Kurihara et al. (1989), substitutions were made as follows: Kalandidi from 198485 rates; Kabat, 198283; Katada, 198283; Lam, T., 198485; Pershagen, 195253; Shimizu, 198283; Sobue, 198283; and Svensson, 198283. 7Worldstandardized rate for 196165 from Katsouyanni et al. (1990) (in Greek: translation provided by Trichopoulos). 8Accrual period value estimated by multiplying LCMR in Shanghai for period 197882 (standardized to the 1950 world population) by the ratio of LCMRs in Liaoning and Heilonjiang to Shanghai, for the period 197375 (standardized to the 1960 world population). Data are from China Map Press (1979). Value for accrual10 years is the 197375 rate. *Data not available.ڐ. For the studies that collected data on both eversmokers and neversmokers, the parameter estimates used are shown in Table C2x(x(#`\  PQP# Table C2. Parameter values used to partition female lung cancer mortality into component sources1 r ddx TDTTT ddx TDTTTr &p@@@@@Pp@@@@@P&܃Eversmokers Neversmokers&cEEEEEUcEEEEEU&CasecontrolLung cancer mortalityPrevalence (%)Relative riskPercentage exposed (%)Relative risk&PP&AKIB6.05212.38701.50&@@&BROW17.29294.30151.50&@@&BUFF15.29597.06840.81&@@&CHAN23.59263.48470.74&@@&CORR26.004712.40461.90&@@&GAO18.00182.54741.19&@@&GARF(Coh)7.002333.58721.15&@@&GENG27.80412.77442.16&@@&HIRA5.70163.20771.53&@@&HIRA(Coh)5.702163.20771.37&@@&HUMB17.704116.30561.98&@@&INOU6.53161.66642.55&@@&KABA13.20425.90600.74&@@&KALA6.58173.32601.92&@@&KOO22.61322.77491.54&@@&LAMT23.46243.77451.64&@@&LAMW22.88224.12562.51&@@&LEE17.11604.61681.01&@@&SOBU7.46212.81541.13&@@&SVEN7.72435.97661.19&@@&TRIC6.40112.81522.08&@@&WU18.15584.38601.31&pp&WUWI11.60372.24550.78 XR1For studies with data on both eversmokers and neversmokers. Table entries are drawn from Tables 58, B11, and C1, which contain explanatory footnotes. 2Average of worldstandardized rates for location during followup period of study from Kurihara et al. (1989). White female rates used for GARF.ڐ. The value for the lung cancer mortality rate is from Table C1, and the remaining estimates are from individual study data. The rate for the followup period of the study is estimated for HIRA(Coh) and GARF(Coh). These values may not be very "representative" for lung cancer mortality in these two cohort studies because they extended over several years, and the LCMRs changed from year to year, particularly in the United States. This same difficulty arises in choosing a "representative" year for lung cancer mortality in the casecontrol studies, although to a lesser degree. The most extreme examples are KABA, PERS, INOU, and GARF, with caseaccrual periods of 10 years or more. The estimates of prevalence of eversmokers and the percentage of neversmokers exposed to spousal smoking are the observed proportions in the control group. The extent to which the control group is representative of the country's population differs between studies; the study reviews in Appendix A provide more detailed information. The restriction of cell types among cases in some studies is another consideration. Active smoking is much more strongly associated with occurrence of squamous and small cell carcinoma than with large cell carcinoma and adenocarcinoma. FONT presents evidence that passive smoking is more associated with adenocarcinoma than with other cell types. As noted in Table 514, some studies excluded candidate lung cancer cases of specific histopathological types. This may produce some bias and distortion of comparison between studies. For example, BROW includes only cases of adenocarcinoma, which should bias the relative risk of eversmokers toward unity, thus attributing too little lung cancer mortality to active smoking and too much to passive smoking and background sources. Of a more positive nature, there is some advantage to using data from a single study to assign attributable fractions to different causes. To estimate the yearly number of lung cancers from each cause, the fraction is multiplied by the LCMR for the location and time of the study; that figure has to be obtained from sources on vital statistics. As seen in Table C2, the mortality rates from lung cancer vary considerably between and within countries. For example, the rates used for studies in the United States range between 9 and 26. Applying the lung cancer rate suitable to each individual study should provide better estimates for comparison within a country than using a single figure for the whole country for some specific year. Despite the reservations described, partitioning the lung cancer mortality for each study into components attributable to eversmoking, spousal ETS, and baseline sources (nontobacco smoke and nonspousal ETS) provides a broad overview worth noting. The calculated values are shown in Table C3x(x(#`\  PQP# Table C3. Female lung cancer mortality rates by attributable source1  ddxog 4"4"" ddxog 4"4"" .8@@@@@@@P8@@@@@@@P.Baseline  sources2  Spousal smoking Eversmoking.EEEEEEEUEEEEEEEU.StudyLocation No.%No.%No. % .@@.AKIBJapan3.47570.96161.6127.@@.BROWUSA8.22480.44 38.6350.@@.BUFFUSA3.34220.00 011.9578.@@.CHANHK14.34610.00 09.2539.@@.CORRUSA2.89110.63 222.4786.@@.GAOChina12.36691.42 84.2223.@@.GARF(Coh)USA3.41490.25 43.3447.@@.GENGChina10.67383.211213.9250.@@.HIRA(Coh)Japan3.28580.78141.6329.@@.HUMBUSA1.57 90.51 315.6288.@@.INOUJapan2.97452.47381.0917.@@.KABAUSA4.32330.00 08.8867.@@.KALAGreece3.04461.39212.1533.@@.KOOHK11.41502.05 99.1440.@@.LAMTHK10.94472.391010.1243.@@.LAMWHK7.35324.852110.6847.@@.LEEEng./Wales5.37310.01 011.7369.@@.SOBUJapan5.05680.28 42.1329.@@.SVENSweden2.19280.16 25.3770.@@.TRICGreece3.42531.71271.2720.@@.WUUSA5.17280.40 212.5869.pp.WUWIChina7.95690.00 03.6531 XR1Rates are per 100,000 per year. Data not available for GARF, JANE, PERS, SHIM, BUTL(Coh), and HOLE(Coh). 2Nonspousal ETS and nonETS sources. ڐ. Estimates of relative risk for exposure to spousal ETS (RR2 in notation of Section 6.3.2) less than 1.0 (see Table 59) were replaced by 1.0 to avoid a negative LCMR attributable to spousal ETS and the consequent inflation of the LCMR attributable to baseline sources and eversmoking. Aside from the studies for Hong Kong and China, estimates of lung cancer mortality due to background sources cluster in the interval 1.5 to 5.5 (excluding BROW, which is strongly biased), predominantly from 3 to 5. The values for Hong Kong and China, however, are much higher, ranging from 7 to 14.5. The presence of indoor sources of nonETS encountered in some of the studies in China may be a factor, but there is no apparent explanation for the outcome in Hong Kong. Assuming that the background rate of lung cancer is much higher in Hong Kong (and possibly China) as it appears, then the question arises as to whether the high excess rate relative to other countries may be attributable to higher exposure to ETS aside from spousal smoking or whether it is more likely due to other causes. Summary data from the 10-country collaborative study of ETS exposure to nonsmoking women conducted by the International Agency for Research on Cancer (IARC) (Riboli et al., 1990) was kindly submitted to us for Hong Kong, Japan (Sendai), and the United States (Los Angeles, New Orleans) from Drs. L.C. Koo, H. Shimizu, A. WuWilliams, and T.H. Fontham, respectively. The average cotinine/creatinine (ng/mg) levels for nonsmoking women who are not employed and not married to a smoker are close for Sendai, Los Angeles, and New Orleans, but they are several times higher for Hong Kong. Consequently, a high contribution to background lung cancer mortality from ETS aside from spousal smoking cannot be eliminated as a factor. X` hp x (#%'0*,.8135@8: