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v Iht. l. Cancer: 39, 162-169 (1987) © 1987 Alan R. Liss, Inc. MEASUREMENTS OF PASSIVE SMOKING AND ESTIMATES OF LUNG CANCER RISK AMONG NON-SMOKING CHINESE FEMALES Litda C. Koo'',1ohn H-C. Ho~, Daisy SAW3 and Ching-yee Hot' 'Dept. of Communiry, Medicine, Universir), of Hong Kong, Hong Kong: 2Radiorherap.v Dept.. Baptisr Hospital; Kowloon, Hong Kong; and 3 /nsriture of Pafhology. Queen Eli;Q6eth Hospital, K'j-lit Road: Kowloon, Hong Kong. Lifetime exposures to environmental tobacco smoke from 28;000 inhabilants/km2, with only 8 m2 of available living the horne or workplace for {i "never-smoked" female lung cancer patients and 137 "never-smoked" district controls were estimated in Hong Kong to assess the possible causal relation- ship of passive smoking to lung cancer risk. lllelative risks based on the husband'>< smoking habits, or lifetime estimates of totai years„totat hours, mean hours/day, or total cisarettest ' day smoked by each household smoker did not show doss response results. Similarly, when such categories as mean hours/day, or earlier age of initial exposure, were combined with years of exposure, there were no apparent increases in relative risk. However, when the data were segregated by histolo=ical: type and location of the primary tumor, it was seen that peripheralitumon in the middle or lower kabes, or, ksss strongly, squamous or smallceil tumors In the middle or lower, lobes, had increasing relative risks that might indicate some association with passive smoking exposure. Epidemiological data linking passive smoking with lung cancer among non-smokers have beemcontroversial. Six stud- ies (Hirayarna, 1981; Trichopoulos et al., 1981; Correa et a1:, 1983; Knoth et a1.,,1983; Miller, 1984; Garfinkel a al., 1985) found significantly elevated relative risks (RR) in the range of 2.0 to 3,5 basedion the smoking habits of the spouse. Five other studies (Garfinkel. 1981; Kabafand Wynder, 1988; Chan and Furtg, 1982- Kooiet al., 1984;, Wu et al., 1985) two of which were conducted in Hong Kong, did not, find'significantl)• elevated RR from inhalation of sidestream tobacco smoke.. Four of these epidemiological studies (Hirayama. 1981; Tri- ehopoulos er al:, 19911; Garfinkel, 1981; Chan and Fung, 1982) defined exposure solely by two questions: whether the spouse smoked (yes/no),, and the number of cigarettes smoked per day by the spouse. Five other studies (Correa er al:, 1983; Miller, 1984; Garfinkel er al:, 1985; Kabat and Wynder, 1984: Wu et al:, 1985)ialso included questions about whether invol- untary smoke exposure had occurred at work (yes/no); and/or whether the parents has smoked (yes/no). Such data seem rather crude indices of exposure, providing only very indirect information on the degroe and amount of exposure. Further- morc, although spouse(s), parents, or co-workers might have smoked; the actual degree of contact of the non-smoker with these smokers could have been very low, or even nil (Fried'- man er al., 1983)1 In our deuiled studies (Koo et al., 1983, 1984) of passive smoking exposures, smoking parents or spouses were sometimes recalled as inflicting little or no ex- posure on the subject. In those cases where, for example, the husband smoked but lived separated from the wife, then our atudy counted such wives as unexposed subjects. Among our never-smoked subjects, this was found to be true for 3 cases aad 3 controls. In order to assess the possible c4usal relationship of passive smoking to lung cancer risk, data from detaile& life-history exposures that were elicited' in intensive 1.5- to 2-hr tape- recorded interviews of never-smoked female lung cancer cases and district controls have been analyzcd. Emphasis is placed on the consistency of the data, the strengths of the RR, and whether dose-response relationships were present. This Rudy of the effects of passive smoking is particularly pertinent:to Hong Kong because it is one of the most crowded urban envirotvnents in the world. Its urban density averages space per person.. MATERIAL AND MFTHODS From 1981-3. 88 never-smoked female lung cancer patients and 137 never-smoked female district controls were inter- viewed as part of a larger retrospective study of female lung cancer in Hong Kong covering 200 cases and 200 controls. In the originai study, patients were matched with an equal number of healthy controls by age (f5 years), district of residence (N=34), and housing type (public or private housing); the latter being an indication of socio-economic status. Details of subject selection, lung cancer histological typing, and method' of conducting the interviews have been discussed elsewhere (Koo et al.,,1983, 1984): Never-smoked subjects wtre defined as those who had smoked less than 20 cigarenes ia the past. All data on passive smoking exposures were double-checked with other data elicited in the life-history interviews, espe- cially residential' patterns since birth (i.e. where t~hey lived, type of housing, number of rooms, number of co-habitants, etc. ), occupations, and marital life to reduce errors in estirnat- ing exposure levels. Among the never-smoked subjects, the rnean age of the patients was 57:8 (5D 10.81) and that for the controls was 59.3 (SD 9.94). This sample included 60 who were widows and 3 who had never married; none had married more than once.. In the design of the interviews, separate data were collected to take into account that within the life-histories of the sub- jects, sidestream tobacco smoke could originate from: (a) different people who smoked in the presence of the subject; (b) different places frequented by the subject; and (c) different types of tobacco. Persons who smoked included related and unrelated members of the household, and even co-habitants who shared an apartment unit (if their tobacco smoke was noticed by the subject). It was difficult to quantify exposure levels from places that could have varying daily amounts of environmental tobacco smoke and were occasionally visited by the subject such as cinemu, while playing majong, or, in transport vehicles. This analysis will only take into account exposures that rcmained relhitivel'y regular during the lifetimes of the subjects i.e. from exposures at horne artd the work- place(s). Among our subjects, tobacco smoke mostly origi- nated from cigarettes smoked by household members, and from pipes (water and regular),smoked by parents or in-laws. In addition to data based onithe husband's smoking habits. 4 other measurenxnts of passive smoking were evaluated: (a)) total years of exposure, (b) total hours of exposure. (c) mean hours/day of exposure, and (d) tota) cigarettes per day smoked by each household member weighed by their years of expo- sure. These measures should be a more accurate reflection of past lifetime exposures than simple questions based on whether the spouse or parents scakcd (yes/no), or whether environ, mental'tobacco smoke was encountered in the workplace (ycs/ no); Rectivedi 1une 24, t966 and in revised form Scpumber 19. 1966 20z351~~ ~"7

PASSIVE SMOtUNG IN CHINESE FEMALES The total years of exposure were derived from adding the years during which tobacco exposure occurred in the home or workplace. Exposures of 6 or more months,were rounded off to the next year. In the home environment, household smokers were only counted if the subject recalled that they had smoked in herprc sence. Where exposure was concurrent, as in the ease of both parents smoking, or exposure occurring at the home and workplace, then the years were not added. The total hours of exposure were caleulated' by multiplying the average hours/day of: exposure by the years of exposure from each~ household smoker, or the amount of exposure at each workplace. Each of these sources of exposure was then added togethenr for each subject. The hours were not added for exposure to simultaneous smokcrs. For example, a husband and son smoking at the same time for I hr would only be counted as 1 hr. The mean hours/day of exposure were derived by addingg the hours/day of home andl workplace exposures and dividing this figure by the age of the subject. This figure approximates the average number of hours of exposure per day experienced by the subject, spread over her lifetime. A weighted average of the total cigarettes per day, smoked by each household member was calculated from the summa• tion of the usual number of cigarettes smoked throughout the day by each household member multiplied by the years that each lived with the subject, divided by, the total years during which cigarette exposure had occurred in the home. This figure ma7- give a bener~ indication of the intensity of cigarette exposure in the home than one simply based on the number of cigarettes smoked per day by the husband, because it accounts for other household smokers and the years that the subject was exposed to each smoker. This figure excluded exposure from pipe smoking and the cigarette consumption levels of co- workers because of difficulties in quantifying those amounts. Of the 88 patients, 83 were typed histologically. Among the remaining 5 cases, biopsy, or cytologic materials revealed that malignant cells were present, but they were too undifferentia- ted or unspecified for categorization by cell!type. Chest radio- graphs were examined for all cases, and the site of the primaryy lung tuttwr-was tlassified' by its location in the bronchial tree, and whether it was centrally or peripherally situated. lm this analysis, the fingula was classified as equivalent to the middle lobe, and peripheral tumors were defined as tltose located beyond the segmental bronchus. Statistical analyses included the calculation of RR as the crude or adjusted odds ratio and tests for trend (Breslow and Day, 1980); Adjusted odds ratios were estimated by the use of a conditional logistic regression package, RECAN, (Lubin, 1981) which was based on~N:M matching by strata defined by district ('N=34)!and housing type (public or private). To take into account the effects of potential confounders which af- fected the RR estimates, adjustments were made for age (<50, 50-69, 70+ ), any formal schooling (yes/no), number of live biiths, and years since exposure to cigarette smoke had ceased in the home or workplace. The exact values were used for the last two variables. Because the resulting large numbers of matching strata in the adjusted odds ratios may lead to unstable results, both crude and adjusted RR were presented for all risk analyses. The Mantel-Haenizel'tesr fon trend was performed on all the crude odds ratios using the midpoint of each interval, whereas the trend test of the logistic parameters was based on, each variabie as a continuous exposure factor. RESULTS To allow eomparii:on of the results of this study with those done elsewhere, exposures based on the husband's cigarette smoking habits were analyzed for the ever-married women 163 (Table 1); In response to the question of whether the husband had smoked cigarettes in the presence of the wife, the crude and adjusted RR were both a non-significant 1.6. RR for the usual number of cigarcnes smoked per day by the husbandAid not indicate increasing risk with higher smoking levels, and the trend tests for the crude (p=0.10) and adjusted' (p- 0.43) RR were not significant. Likewise, when the data were analyzed in terms of cigarette smoke exposure during childhood/adulthood, or by, the num- ber of smoking co-habitants, as in the study of Sandler rt al.. (1985) (Table 11); no consistent pattern emergedi RR at the higher levels of exposure, i.e., both childhood and adulthood,, or 2+ smoking co-habitants, were found to be lower than those at lower kvels of exposure. Lifetime exposure nttcs+urmrrus When the crude and adjusted odds ratios were wlculatod.for ft4 lifetime exposure tneasurements;.ihrc !tR fos the iiuer- tmodiate exposure levels of tneatt bours/day (1.94 lutd 4.10), and cigarettes/day (1.57 and2.36) were significant (Table III). However, with the exception oftoul years, all of the RR (0.9- 1.4) at the high exposures were below those of low or inter- mediate levels. Even for total years, the Mantel-Haenszel linear trend test (ps0.55) for the crude RF, and the trend test for the logistic adjusted parameters (p-0.23) indicated that the pattern was insignificant. When the crude and adjusted RR are compared (Fig. 1), the adjusted RR fon these measurements showed RR fluctuating between wider: ranges of 1.0 to 4: l, yet both lacked evidence of a consistent dose-response pattern. Imtruir). As a measure of intensity; RR were ealculated to see whether there was a direct relationship between increasing years and mean hourstday of exposure in a 2 x2 table (Table IV). Start- ing with the top left-hand square which was the group with the lowest exposure levels, one would~ expert RR to be higher in all the other squares, especially the one at the lower right~ because it had the highest years and mean hours/day of expo- sure. However, the crude RR at this highest intensity level was only 1.07, and the category with the lowest intensity values (top left) had the highest adjusted RR of any of the other groups. A similar panern~ emerged if total hours or eigarettes/day were substituted for mean hours in this anaJysis. Age of initia! tzposurt We had previously found no difference in the age at which passive exposure had started (Koo rr al:, 1984). To set whether earlier age of initiall exposure combined with higher years of exposure were related with increasing risk, RR were calcu- lated for cigarette exposures in a 2 x2 table (Table V). Again, we did not see any panern suggesting a dose-response relation- ship. The top left square with the least years of exposure and older age at initial exposure had the highest ctudeand adjusted RR. Similar results were obtained if the years and age of exposure included al1 types of environmental tobacco smoke, i.e. from cigarettes and pipe. Histological rypr The cases were divided into two groups, those with squa- rnous or smallixll lung tumors, and those with adenocarci- noma or, large-cell~ lung tumors. This division was made because the former group was previously found in Hong Kong to be more related to active smoking than, the laner (Koo et 01.,,1985). Five cases with mixed cell types and 5 with unspec- ified cel)itypes were excluded from the analysis. Although notx of the crude or adjusted RR or trends by histology were found to be significant, it can.be obsettied that a dose-response pattern seemed to be more apparent among

164 KOO'E7 AL. TAiIE 1.- HUS6AND'S CIGARETTE SMOKING HA61TS#NDRR FOR LUNGCANCER.AMONGEVER-MARRIEDWOMEF Ex.p- Num6rr of carV .rm6tr d a.ard6 C~ RR (95; CI/ Adtuued RR' (9Sf C11 Husband ever smok'edo7 No 35/70: 1.00 1.00 Yes 51166 1.55 (0.94, 3.09) : 1.64 (0.87, 5.09)', Cigarenes/day Rmohed by husband 0 32/67' 1.00 1.00 1-10 17115 2.37 (1.03. 5.91) 2.33 (0.92.,5i92) . 11-20 25135 1.50 (0.87. 3.64) 1.74 (0.81„3:75). 21+ 12119 1.32 (0;45, 2.63) 1,19(0.46.3403) rAdjusted fa aae.+.rmAe* of I..e b+rtM. scMdmg t+!-1:andyeansinnteposurc to crEsrcne smoke eeasad in d.rliorneor .otkp4ace.-7Hus6.n0 tmotnd mtAe preaencs of tht rrfe. 3 oses ud 3 mwtrrols .ere oa espo.eG so Me ctpreoes of theu. IiusbanQ. TARl3: 11 - RR.FOR LUNG CANCER FROM' HOUSEHOLD EXPOSURE TO CIGARETTE SMOKE F-pW R Ninnberofcasca!' aum4tr o(m+rrol~ pYpeRR'(95.i:C11 AOfur.dRR~..r95R.C11. By period in life No exposure 27/49' 1.00 1.00: Children onlyy 2/3 1'.21'(-) 2.07'(0.51. 95.17) Adulthood only' 57/77 1.34 (0.84. 3,01) 1.68'(0.62. 5 45) Both childhood + adulthood 2/8 0.45 (0.11, 3.32) 0.64 (0.57, 5.85) By number of smoking co-habitancss None 27149 1.00 1.00 - 1 49168 ' 1.28 (0:82, 3.25) 1.73'(0.i7,6:35) 2+ 13/20 1.18 (0.57. 3.65) 1.35 (0.64. 5.03) 'Crude atSds ntio.-yAd)ursted fovage, number of IirebirtAse schodmj (•!-): and yean uas r:powr: lo cipnene smoke eened m tM Honr or -oatplact -'From one or bollh panenas. `Fromspoute. L,.)ars. Mildren...o. a4er eo4.Eiunu.-s From, spoure. pnenu.,arLvs. ehu)dho..or ertlrr oo-A.ti.unuwhonnoLed u'Iiomein.tM prernce of tlie wbjecn.. . , TA1LE III - MEASUREMENTB OFPASSIIlE SMOKING AND RRFOR LUNG: CANCER Taa6 yeart HaTM!de> . Eapown ~s RR'.f9ST.C11: RAr(93{ CI). Eropoare ~ vy RJl'.'19S{ CI/ RR~ f9S4 CI). 01 22/40 1.00 1.00 0 22/40 1.00 1.00 1-19 . 20/28 1.30 (0:63, 3.68) 1.95 (0.72. 3.31) < 1' 15/29 0.9d'(0.41, 2.63) 1.05 (037. 2.94) 20-34 24739 1.12 (0j59:,3.06) 1.36 (0.35, 3.36) <2 33/31i 1.94 (1.24, 6.74) 4.10 (1_59; 10.6)) 35+ 22/30 1.33 (0:79, 4.44) 2.26 (0.90. 5.67) 2+ 18/37 0.88 (0.42, 2.42) 1.00 (0:39; 2.58) Totel Awn (a Aadnds) Clterenm/d.yt Eapr.ne ~ CAWV s 1lR' (93f CI/. ~ RJt7,(45R Cq IEsoaure e~~s RR' (9S4 Ct/. l RR7 (93f Cl) 0 22/40 1.00 1.00 0 25/48 1.00 1.001 1-10 25f38 1.20 (0.60. 3.67) 1,68 (0.64;4.43) 1-10 13/16 1.56 (0.~74„4.96) 1.83 (0.65,5.11) 101-200 23/27 1.33 (0.88, 3.33) 2.28 (0.91,3.72) 11-20 27133 1.57,(1.00:4.99) 2.56d1.06. 6.19) 201+ 1g/32 1.02 (0.54, 3.47) 1.42 (0.56. 3.62) 21+ 23/40 1.10 (0;51. 2.47) 1.21(0.51, 2,86) rCrNde oddf.rtll0.?AdJu{le0 for age, Qlmbet of IIYe.brnbi. KII001lng (+)-). and ytann e1Kt etPOHtnt to c1`lrCneemOtt:[OMdin the home or - 'olf:pllree -r 1s autn of number of cipnenrsFd>,)strntad eacA AourelrofQ member rreigAwd Ey IAe yean of e.posun from tAau wurce k4mellHaensxdJ trend amalysu. Ynrs 0.55. Aoun:. 0.73. AwrVd.y:.0.70. ciR/d.y. 0.67.isuc adyumd dresd analyus. Yean: 0.123. /nun. 0.91. 6nurs!d.y: 0.66. cq!diy: 0.63. TAStE IV.- EFFECTS OF INCREASfNO YEARS AND MEANBOl1RSiDAY OF TA1SF V - FFFELTS OF INCREASING YEARS AND EARILER AGE OF INITW: TOlACCO EX!'06URE EXPOSURE TO CIGARE7TE SMOKE 1Ws d sap- 1-24 23. Mean hours per day of exposure RRI' RR2 RRI RR2 <1.5 1.3- 3y- 2.22` 1.47 2.13 (19l26)° (21 R6) > 1.5 1.02 1.21 1.07 1.45 (9/I6) (!7/29). Vrn d esp wrt 1-74 Agc at first exposure RR'' RR7 RR' RRI =25 1,30 1,.95' 1.30 1.67 . (20/25)s (Sr40) C 24 1.00 1.35. 1.23 1.86 (g/I5) C281421 rCnade odds raio:-2AEjuuedfor ar. vmbnof.lrve births. eelndiey (+t-):, and~ytan since eapoaure to cnprear snnte wselrn the honx or.wrtyAct-195x rCrudr odds ~ruw -=Adjms+edW for aje, aumbcrW Irve birdu. se6oolrn` (+!.-)~. aM jYan una~ eapowre to cra.rene vnMr orased re the honr or .ortyi.or~ -s93 S ~ ~ 3 451. 1.07 (0.57. 3.39)'. 1.02 (0!39.. 430) 4 00) 1 47 f0:74 C[ 1 33 (0 6d CI 1.50~~10,71..3~99). 1 50 0 (0~47. 4.6t). .00 (0~41. 1 3~4?). .25 (0~76..360) 1 . .. . . . . . . -•95R CI 2:22(0.)9.6.21). 2.13 (0~is..SS3):. 1.21 (D.37. 3.96.). 1;.45 (0;56.. -e95T Cl: 1 93 (0:76..e 961. 1.67 (0.55~. 5131. . 1'.35 (0 30. 6~161:. 1.l6 (0 7!. ' ~ ~ 3:76) -sNum6cr o/ ords!rrmber ofor.nots. 22 casea and 40 oomd+ aed ao tapnrme - RR 1.00. ~ m , 455 onrvois Aed osae/humbtr of nonerois 24 nses ard 4 .46).-sNumbcr of etpc.urc • RR 1.00 :©2351277-9

IASSrVE SMOKING IN CHINESE FEMALES ... ... • a.w.. ..+. e...,..,..... ..M .... ,.,.. +.. r.." ... FIGURE l- Measurements for passive smoking and RR'for lung un- cer. •Adjusted'for age, numbcnof live births, scliooling (+1-) and years since exposure to cigarrne smoke ceased in the home or, work- place. p tc 0.05. 165 the squamous or small-cell lung tumors than among the ade- nocarcinoma' or large-cell types (Table VI). This was espe- cially, true for the adjusted RR' in the former group, as 3 of the 4 measurements consistently indicated increasing risk with, increasing exposure. l.ocnrron by lobe Eighty of the cases had the main tumor residing in one of the lobes. The remaining 8 cases, with primary, tumors in the right or 1efi'mainDronchus„or in the right, imermedius region, were too few for analysis. Calculations of the RR showed that none of the crude or adjusted values were signifiunt for upper,lobe rumors (Table VD): For the middle or lower lobes, all of the adjusted RR were in the comparatively higher range of 1.9-3.5 for those with some passive exposure.~ Moreover, for 3 of the exposure measurements, total years, Murslday, and'cigarenesAday, the confidence intervals for the crude and adjusted RR indicated some borderline significant values. However, none of the trend analyses for the lobe data esme out signifiunt- TABLE VI - MEASUREMENTS.OF PASSIVE SMOKINGAND RR.FOR LUNG CANCER aY'1flSTOLQGICALTYrE NunMer of ou.l wrmECrert af.rb/ts Toul years 0 7/40 1-26 10/46 27+ 15/51 Toud'.hours (in hundreds): 0 7/40 1-150 12/56 151 + 13/41 Hours/tlay 0 7/40! < 1.3 8/44 = 1.3 ~ I'7/53 Cigarenes/day 0 9148 1-1I9' 9/26 20+ 14/62 SQ.Mnpr> d.OlY11Ke11 Adnoom.an. a Wfrssll NumEe. of c..ev' RR'(93li.Cl). RR=1PbSCII.nnbnd RR'!4lSCq RR'/h6CI/ taarol: 1.00' 1.00' 12/40, 1.00 1.00 1.24 (0.37;5.40) 1.58 (0.37. 6.77) 17/46 2:11 (0.54. 3.74), 2.07 (0.64. 6.71) 1.68 (0.47; 5.79) 1.82 (0.49, 6.80) 17/51 1.90 (0.51, 3.27) 1.43 (0.51, 4.02) 1.00 1.00 12?40 1.00 1.00 1.22 (0.34, 4.71) 1.40 (0.34. 5.77), 18/56 1.07 (0.48. 3.05) 1.70 (0.55. 5.20), 1.81 (0.52, 6.54) 2:04 (0.53, 7.85), 16/47~ 1'.30 (0.59, 4.02) 1.57'(0.55, 4.49): 1.00 1.00 12/40 1.00 1.00 1.04',(0.31, 4.70) 1.34 (0.31, 5.84) 17/44 1-29 (0:56, 3.61') 2.19 (0.71, 6,77)'. 1.83 (0.52. 6.69) 2.0U(0.52,7.72) 17/53 1.07 (0:49;,3.23) 1.34 (0.47, 3.82), 1.00 1.00 13/48 1.00 1.00 1.85 (0.57„7:20) 2.02 (0:53, 7.68) 12/26 1.70(0.77; 5.72) 2.05 (0.63, 6.72). 1.20 (0;36. 3.31) 1.19 (0;36, 3.93) 19/62 1.13 (0.59, 3.57) 1.88 (0.68. 5 17) rCeude addr ntw -=Adju+oed fer ate. eumber of 4rve bbrtlu. .ehmlint (•/-1. lud'ryonuna eapowrc lo npreae wrok'e aaced mtAe 6onK or .atipl•tt. TAELE %9t.- MEASLIREMENTS OF PASSIVE SMOKlNGANO RR FOR LUNG CANCER BY LOBAR IACATION'. Uppr, kEn Mddk w lorer Icbn Nwnsrr of nn,, nrmEer uf c..rrul. RR' (4S7 Cr) WNSf Cll Nrn+ber d.nx•" rrrnher. dronrod.. RR' (95:7 Clf~. RR'i151 CII Taul years 0 10/40 1.00, 1.00 11 /40 1.00 1.00 1-26 11146 0.96 (0.43, 3.82) 0.98 (0.27. 3.64) 17/46 1.34 (0.86. 8.72Y 3.08 (0.83, 1:1.38). 27+, 16/51 1.25 (0.40, 2.87) 1.42 (0.46.4.42) 15/51 1.07 (0.62, 6,15)~ 2.13 (0.62,7.24) Total hours (in hundreds) 0 10/40 1.00 1.00 11140 1.00 1.00 1-150 15/56, 1.07'(0.30, 2.38) 1.30 (0;38; 4.50) 16/56 1.17(0.76- 7.26)' 2.37 (0,67, 8.35) 151+ 12/4) 1'.17'(0.38, 3.01) 1.23 (0:39;,3:91) /4/41i 1.24(0.68, 7.17) 2.51 (0i72. 8.84) Hours/day 0 10/40 1.00 1.00' I7/40 1.00 1.00 < 1.3 7u4 0.64 (0.15, 1.58) 0.69 (0:18; 2.61) 17/44 1.40 (0,95.,9.51) 3.24 (0;90: 11.66) ;1, 1.3 20153 1.51 (0.51, 3.70) 1.64 (0.54, 5.01) 15/53 1.03 (0!55„5.55) 1.97 (0:57„6.82) Cigartrtu/tlay 0 10/48 1.00 1.00 12/48 1.00 1.00 1-19 I0/26 1.85 (0.57. 5.39) 2.32 (0.62, 8.76) 12/26 1.65 ().08. 10.39) 3.49 (0:98; 12.50) 20+ 17/62 1.32 (0.48„3.32) 1.79 (0.59, 5.45) 17/62 1.1'0 (0:61. 4:61) 1.93 (0:63, 5.95) rUrOr oddl nuo _1Adpmed far qc, .rnbe+ of.lin brdr. •ebooiina (+! - ), ad yaan u= e:ysci-re roo eapreoe aqte cramd m, tlie Anor a.orlpl.cr.

166 KOO EZ AL. Praxi ino!/prri phtral locarion Among the 85 determinable cases. 46 had peripheral tu- mors, and 39 proximal tumors. Although only the crude RR of~2,00 and adjusted RR of 3.52 for 1-19 cigprettes/day were slightly significant for the proximal tumors, in general, all of the crude and adjusted RR for the peripherall tumors were greater than 1.00 (Table VIII). Hisrological rW and location In order to set whether any, particular combination of histo- logical type, lobe, or proximal/peripheral location of the tu- mor would result in stronger dose-response patterns by the 4 lifetime rtteasurements of passive smoking. RR were analyzed for the 12 possible 1:1 combinations. We were unable to segregate the cases into any finer categories than 2 of the 3 groups because of, the small resulting number of cases for analysis. Space does not allow us to present all the tables, but the best combination was that of peripheral tumon in the middle or lower lobes (Table IX). Among the RR, signifieant or nearly significant figures were found for the crude or adjusted RR relating to at least one of the exposure categories for each type of measurement. Moreover, the adjusted RR tended to range between the relatively, high values of 6.5 to 18.7 for those with some exposure (Fig. 2). and most of these were significant or nearly significant. None of the trend tests came our significant, but this and the tendency for the higher kvels of exposure to have lower RR than the low levels of exposure may have been due to the small number of cases QV=24): Although not as apparent; squamous and small-celll lung cancers in the middle or lower lobes (Fig. 3) also seemed to show some positive association with passive smoking.. There were only, 18 cases with this type for analysis and none of the RR or tests for trend were found to be statistically significant (Table X). Yet it was promising to see that all the RR with some exposure were greater than 1.0. Among the highest exposure levels for the adjusted RR, values as high as 7.0 were found for total ihours, and 6.2 for hours/day. DLSCUSSION For comparative purposes, the more corrunonly' used mea- surements of passive smoking based on yes/no questions of whether household co-habitants (husband, childhood/adult- hood, or others) had smoked, or on the number of cigarettes the husband smoked per day, were presented. Only the crude RR of 2.37 (95% CL 1.03-5.91) for husbands srnoking I-10 cigarettes/day was of borderline significance and none of the adjusted odds tatios were significant audx 45% probability level. There was little indication that increasing levels of such exposure led to increased RR. On the basis of our extensive life-history data, we were able to calculate the total years, hours, mean hours/day, and ciga- rettes/day to which the subjects had'been exposed to tobacco smoke at, home or at work. Our estimates were based oo the understanding that the household' composition of each subject would change as she progressed through the lifetycle of birth, childhood, adulthood, marriage, motherhood and, for 27%, widowhood. We also included exposures from each workplace at which t}ie subjea had~worked for at least 3 months. In our adjusted RR, the effect of rxssation of exposure to passive smoking was accounted'for by putting in the years that expo- sure had ceased at home and/or workpl6ce as a continuous regrCSSor vartable.. Despite such d'etailed accounting, we were unable to find a stgn ficant trend in the crude or adjusted RR for these 4 lifetune measurements of passive smoking. Although the RR for the intermediate level exposures of hours/day .nd eiga- Y ~ o< w r •. oa l: 0 / --ci9 roay 2.00 1.00 0 ~-~-- None Lovr ~ High Exposure Levels FIGURE 2'- Measurements of passive smoking and RR for peripheral lung cancers in the middle or lower tobes_ Adjusted odds ratio. 6.00 7.00 6.00 i[ w 5.00 a , 4.00 a : a a.0o 2.00 1. 00 0 . None . Low Eaposure Levels ; Total hours Niyh FIGURE 3- Measurements of passive smoking and RR for squamous and small-cell lung cancer in the middle or lower lobes. Adjust ed'odds nuio. rettes/day were significant, the RR at the highest levels of exposure for these two variables fell to a rwn-significant 1.0- 1.2. in fact, the RR' for the highest exposure levels for 3 our of the 4 measurements were below all of those with lower exposures, and ranged from a very weak 1.0 to 1.4. On the other hand, most of the crude and adjusted RR were greater than 1.00. 2023512781

-ASSIVE SMOKINGIF CHINESE FEMALES TABI.E VIII- MEASUREMENTS OFPASSIVE SMOKING AND RR FOR LUNG CANCER BYtOCATION Of TUMOR RR"f9S% CII RR~ f4SS CIi Toul lyears 0 Ii0/40 1.00 1.00 1-26 18/46 1.57 (0.39. 4.94) 1.52 (0.44. 5.17) 27+ 18/51 1.41'(0.64. 4.78) 1.84 (0.62. 5.45) Tonl hours (inhundrods) 0 10/40 1.00 1-150 20/56 1.43 (0.63,4.97) 1:51+ 16/41 1_56(0.60,4-71) Hours/day 0 10/40 1,00 < 1.3 14/44 1.27 (0.56. 4.62)' > 1.3 22/53 1:.66 (0.66. 4.98) Ciprsaes/day 0 12/48 1.00 1-19 . 11126 1.69 (0.73.6,14) 20+ 23162 1.48 (0.70. 4.34) Nurrrf~r~nf w+cs! wnMrr n( tcnud~. RR' fPSf CI) RRI(954 CI) 167' 11740 1.00 11.00 14146 1.11 (0.30, 4.14) 2.15 (0.64, 7.19), 14/51 1.001(0.43, 3.51) 1.38 (0.51i 4.92) 1.00 1 1/40 1.00 1.00 1.92i0.57, 5.85), 16156 1.04 (0.46, 3.53) 1.86 (0.58, 5:97) 1.66 (0.54. 5.06) 12/41 1.06 (0.47, 4.19), 1.72 (0.54. 5.51) 1.00 11/40 1.00 1.00 1.66 (0:52.5r33) 13/44 1.07 (0.48, 3.94) 2.21 (0.63, 7.75) 1.77 (0j 59;5.32) 15/53 0.89 (0.44, 3.69y 1.59 (0.51, 4.93) 1.00 12146 1.00 1.00, 1.91 (0.57. 6.35) 13/26 2.00 (0;98, 9.17) 3t52 (1.01, 12.27) 1.79 (0.64. 5.03) 12/62 0:77 (0:34, 2:45) 1.23 (0.42. 3.62), rCwde odds ratio -=Ad)usud (or are. eum6er oflive DrnAs. achoolinR 1+ /- ). and years since er.po.unr ro cip+ene anoicmsad m tAeliane or wor1p(acc TABLE IN - MEASUREMENTS Of PASSIVE SMOKING AND RRFOR PERI-HERAL LUNG CANCERS INTHE MIDDLE ORLOM'ER LOBES ELpO!YIR Nirnprr of ca`ts' wmrb[r Mcanirdr RR'(9Sa Cli RR=(95f Cal Toul years 0 4/40 1.00 1.00 1-26 110/46 2.17 (0 98. 84.95) 10.44 (0.91, 119:53) 27+ 10151 1.96(0!88.66.91) 6.61 (0.84, 88.21) Toul hours (in hundreds): 0 4/40 1.00 1.00 1-150 12/56 2.14 (1.24. 110:17) 13:51(1.16, 157:74) 151 + 8/41 1.95 (0.69, 56.35) 7.02 (0.64, 76.93) Hours/day. 0 4140 1.00 1.00 < 1.3 11/44 2.50 (q.71,160.18) 18.70 (1.53.228.03) ;t 1.3 9.'53 1.70 (0.62. 49.89) 6.49 (0.60, 70.37) Cigtrettes/day 6/48 I.00 1.00 1-19 6126 1.85 (0.95. 24.36) 5.53 (0.79, 38.86). 20+ 12/62 1.55 (0.74. 13.14) 4.16 (0.77. 22.55) 'Crustoddsrnro -2Adluard for aEe. tirn6er of Ine bbrtlu. teMMmR and yesr. unaeapoaure ronpnne anake eea.ea:rn the IuveK or morhplaec Mrmel-Haen.ulrrendan.lysi.Ynn01S.Aoun0.16.Aoursadn0~14.cq)dn~ 0.19 LoEiuic adjusmd trend analysis Yrin 0, 15. Iiaun 066. Mon.lda) 0.53. cug'dL;y 02:. TABLE X - MEASUREMENTS OF PASSIVE SMOKING AND RR FOR SpUAMOUS AND SMALl{ELL LUNG CANCERS IN THE MIDDLE OR lAx-fR LOBES Numlrr efcrr., rlllAtfnr CAIrRrI. RR' IKs Cb RR-, (9Sf CI) Toul years 0 3/40 1.00 1.003-26 7/46 2.03 (0!52. 44.44) 5.29 (0.51, 54.71) 27+ 8/51, 2.09 (0:42. 33.01) 3.97 (0.41, 38.22) Tauldwurs (in hundreds) 0 3/40 1.00 1.00 1-150: 6/56 1.43 (0.35. 29.32) 3.44 (0.35. 34.17) 151+ 9/41 2.93 (0.59, 46.98) 7.01 (0.64, 76.60) Hours/day 0 3/40 1.00 1.00 < 1.3 4144 1.21 (0.30, 29.64) 3.05 (0.28, 33.14) ;t 1.3 11/53 2.77 (0.57, 44.05) 6.16 (0.59, 64.48) Cigarmes/day 0 4148 1.00 1.00 1-19 V26 2.31 (0.58, 23.25) 3.97 (0:54, 29.20) 20+, 9/62 1.74 (0 44„11.87) 2.58 (0:42; 15.93) 'CNde odds nua.-=AEpned(or F. -wrEa of In'e EiAln. W-enlu+j (+1- ), Md r{fn ofne eaPMrR b caBaMle smoie oraind in Nr honY a.atplaae IA.rnel-Haen=c( nend:^naiysn Years0.23, Aoun 0.20.lioun+dly, 0.26. nEldiy0.20 LOsW K ad)uptd OCfd aY1ym: Ysn: 0 A) . lnun L 0.76. Mourijd+y 0 .70: c3q)4ay. 0.7t

168 ttoo E-r AL. Measurements based on increasing intensity of exposure, defined as increasing years (or hours, or cigarettes/day) by mean hours/&y of exposure, also did not indicate a dose- response relationship. Likewise, the analysis of total years of exposure withage of exposure did twt suggest that earlier age of initia)i exposure and increasing years of exposure led to higher RR. Ih was troubling to find that in both types of analysis, the RR for the lowest amounts of exposure were among the highest values. Dalhamn cr a/: (1968) noted from their study of the retention of cigarette smoke components in human lung, that water- insoluble volatile compounds and particulate matter from cig- arettes tended to be deposited pritnarily in the deeper paru of the respiratory tree. Since adenocarcinoma is predominant among non-smoker lung cancer cases (59 96 of our typed cases) and it is generally a peripheral tumor, we wanted to see whether the passive smoking measurements would exhibit a more consistent pattern among the adenocarcinoma and large- cell types, andYor among the peripheral tumors. In general, the pecipheral tumors as a group showed stronger dose-re-e sponse results than the adenocarcinomas. - The RR for total years, hours, and hours/day measurements of squamous and small cell lung tumors indicated consistently elevated risks with increasing exposure. This pattern was not found for any of the adjusted'RR for adenocarcinoma or large- cell lung cancers. This association of histology, with passive smoking is alsosuggested from previous studies by Trichopou- los cr al. (1981) and Correa cr al. (1983): Analysis of the cases by the lobe location of the tumor was done to see whether the primary tumor resided more fre- quently in the upper lobes than in, the lower lobes. This is because it is known i that when dust is inhaled, it first enters the upper lobes where much of it is deposited. and then travels down to the lower lobes (Time. 1980). Furthermore, it has been observed (J.H-C Ho, personall observation) that up to half of the Hong Kong adult population have radiologically evident scars on the upper lobes of their lungs. Most of these scars are due to previous tuberculosis infection. Since "lung cancer is more common in the scarred and chronically diseased lung" (Stone et al., 1978), we were interested to see whether the lobe data would substantiate any of these possibilities. In fact, 37 of the lung cancers were found in the upper lobes, and 43 in the middle or lower lobes. The results from the RR estimates from~the 4 types of measurements did not show the upper lobes to be more sensitive to environmental tobacco smoke. Wynder and Goodman (1983) suggested~ ahat lung cancer in non-smokerswas more likely to occur in the periphery of the lung. This was found~in our study, as 54% of the determinable cases had peripheral tumors vs. 46'i(o with proximal tumors. Moreover, the pattern of RR with the various measurements of passive smoking indicated that peripheral tumors seemed to exhibit berterdose-respottse RR than proximal~tumors. When the liR were calculated for the 12 possible 1:1 emn- binations resulting from histological type, {ocation by liobe, or pt•oximal/prn pheral turnors, the hi.gheu RR were found for peripheral tumors in the middle or lower iobes. Significant adjusted RR as high as 18.7 were found for some of these measurements. Although RR at the lower doses, tertded to be higher than that for the higher doses, the data were consistent m that all the RR for those with some exposure were much greater than 1.0, and the adjusted RR for at least one of the RR for each type of measurement was statistically significant or ncariy sigtu'ficant. The RR analysis for squamous and smali-ccll' lung cancers in the middle or lower lobes also appeared somewhat better than the others, with toulihours and hours/day measurements showing some dose-response pattern, With the above two combined analyses showing some promise, perhaps the best RR would have been obtained': iflanalysis hadibern done with squamous or small-cell' peripheral tumors in the middle or lower lobes. We were unable to do these calculations because only 8 cases fined into this category:. Actually, the finding of a possible risk of squamous and, small-cell tumors in the middle or lower lobes was somewhat unexpected, given that dust particles tend to adhere to the upper lobes, and tuberculosis usually affects the upper lobes. To see whether talcified foci or fibrosis in the upper lobes could account for the higher RR in the middle or lower lobes because the previous presence of such lesions might disturb the expected~ distributiorn of inhaled particulate or gaseous matter, rnost of the chest radiographs of cases with squamous and small-cell lung tumors were re-examined. No significant difference was found in the proportion of positive cases with upper lobe vs. lower lobe tumors. In our analysis of all never-smoked cases, the lack of a dose- response panern, and an almost consistent drop inithe RR at the highest doses of exposure would seem to lend little, or only weak suppon for the passive smoking linkage with lung cancer for women in Hong Kong. This might be due ro the fact that it has been estimated (Rylander ci al., 1983) tlianthe non-smoker exposed to environmental tobacco smoke receives about 1% of the active smoker's dose of tobacco smoke based on cotinine levels in the body, and this is roughly equivalent to the tobacco smoke of 0.1-1.0 cigarene inhaled by an active smoker in a day. Moreover, a 1S- to 17-year longitudinal study of 97 non.srnoking females in Holland did non find an,associ- ation between passive smoking exposure and pulmonary func- tion decline (Brunekreef cr al., 1985). Thus the effects of passive smoking might be so weak that they arc easily over- shadowed by other environmental factors such as diet or ex- posure to inhaled gaseous/particulate matter from other,sources in the home or the workplace. When the lung tumors were segregated by histological type and loution, the resulting analyses showed' that peripheral tumors in the middle or lower lobes, and squamous or small+ celi tumors in thc same lobes, exhibited better, RR patterns for passive smoking in terms of consistency, strength, and dose- response. We are not sure whether this prociivity for passive- smoking-related lung tumors to reside in the middle or lower lobes might be due to the fact that the lower, lobes have more bronchial cells at risk than the upper lobes,, or whether the size, weight„or composition of gaseous or particulate matter from passive smoking may favor its adherence to the periph- eral areas and'the lower lobes. Nevertheless, the overall' pro- portion of lung tumors in the middle or lower lobes among our 88 cases ranged from 27% for the peripheral tumors to 20% for the squamous or small-cell tumors. Thus, the majority of lung cancers among our non-smoking population were proba- bly due to some factor($) which yerrematn to be identified. The results from this study, showing a weak effect of passive smoking on the risk of lung cancer among never-smoked Hong Kong Chinese women, must,be interpreted nutiously, since it was based on only 88 cases and 137 controls. Widt this sample size. R3t less than approximately 1.4 would be difficult to detect with 95 % power and at the S9f> level of significance. This problem was even greater when the cases were stratified by histological type and location of the primary tumor. How- ever, these data seem consistent with the findings from other epidemiological, biochemic.al, and physiological studies in showing higher ri'sks for squamous-cell tumors in the periph- eral areas of the lung. Confirmation of these findings from ottier studies is therefore needed. ACKNOWLEDGEMENTS We thank the Hong Kong Anti-Cancer Society and the Uni- versiry of Hong Kong for financial assistance in the carrying :02351~:783

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