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lMIEVE`1TIVE MEDICIlrE 13, 68o-69Qd1984) . r Cancer Mortality in Nonsmoking Women with Smoking Husbands Based on a Large-Scale Cohort'Study in Japan' TAKESF~~HIRAI'AMA Naiional'Concsr Centrr Rtsrarrb /nsritrur.~l-1 TsukjJi S-cbrnnt. Cliun-tw: T~+Lcn104. Jupan Mortality of 91.510 nonsmokittg; wives was studied in relation to the smokins habits of their husbands by means or a cohort study in Japan. During 16 years of follow.up. 200' dsaths from lung cancer took place. The relative risks of lunj cancer in these nonsmoking wives were 1.00. 1.36. 1.42. 1,58. and 1.91 when husbands were tansmok'en. ec•smokers. or daily smokers of 1-14. IS-14. or 20 cr more cigarettes daily, respectively. Correspondine relative risks for stomach cancer were 11.00. 1.16: 1.00, 1.00. and 1.01. respectively. Spec• dcity of association and internal consistencies were observed. Among cancers of each site.. a similar tendency toward risk elevation in nonsmoking wives witli smoking husbands was observed for nasal sinus uncer. brain tumors. and cancer of all sites besides lung cancer. In imeryrtting these results. the significance of prorcimity in exposure to sidestream smoke in Japanese homes was stressed. c ttw Ac.u.w ns.+. uc- INTRODUCTION The possible health hazard due to passive smoking was evaluated by the ob- servation of mortality in nonsmoking wives with smoking husband's. As reported previously (6). nonsmoking wives of heavy smokers had a significantly elevated risk of lung cancer. Results of our large-scale cohort study reported here not only confirm the results of the previous Ireport, but also reveal additional evidence of the health consequences of passive smoking by pointing out excess deaths due to cancer of other selected sites. MIATERIALS AND METHODS A prospective cohort study on the health consequences of cigarette smoking has been in progress.in Japan since the fafl of 1965. !n total. 265.113 adults (122.261 men and' 142.857 women) ages 40 years and above. tA4.8~7c of the census population in the study area in 39 Health Center Districts in Japan. participated. They, were interviewed from October I to December 31, 1%S. and have been tracked by establishing a record' linkage system between the risk factor records and death certificates. The 16-year follow-up results of this census-populatiQn-based cohort study were used as the materials for the study. RESULTS In a large-scale cohort study earried' out in Japan from 1966 to 1981. non- smoking wives with smoking husbands were found to carry a significantly ele- t Presented at the Symposium "li/edieat' Pt:rspeetivci. on Passive Smoking." April 9-12. 1963. vienna. Auslria. 0091•745514 53.00 . Cap.rmriM i IR+.M AM ry1is. u(rewwM-.~ . aaw. ir.w wv..N 6S0 ~ ~ ~Wa W(~ ' 1..~ N ~

SYMPOSIUM: MEDICAL PERSPECTIVES ON PASSIVE SMOKING 681 vated risk of lung cancer (n = 200). nasal sinus cancer (n - 28). brain tumors (n - 34). and cancer of all sites (e =?705). Lung Cancer A total of 429 deaths from lung cancer in women was recorded during the 16 years of follow-up (1966-198M Of these deaths. 303 occurred among nonsmokers and 200, among 91340 nonsmoking married women whose husbands' smoking habits were known. ,- dl'be stattdalydi:ed mortslity rafios'"~MRs)ttlf.lung sancer_in tnonsirtok;tig'women -- +rt~e 1.00. 1.36. 1.42.-1.58. and 1.91 when husbands were nonsmokers. ex-~',7' lmtokerso or daily smokers of 1-14. 15-19. or 20 or more cigarettes per day. >rcspective4y (one-tail P value - 0.00178) (Table 1). A similar dose-response relationship was observed' by age and occupation of the husband (Table 2). '~ This tendency is in sharp contrast with that of stomach cancer, where no re- lationship at all exists between the risk in nonsmoking wives and the amount of smoking by the husband (Tables 3 and 4. Figs. I and 2). Similar trends of lung caneer risk elevation in nonsmoking women with the increase in the extent of the husband's smoking were observed in each time period of observation. in each age group. both by age of husbands and by age of wives, in each occupational' group; and in most areas under observation (internal!con- sistency) (Fig. 3) (7). No other characteristics of husbands or wives themselves were found to elevate the risk of lung cancer in their nonsmoking partners (7) (Table 5). :kNonsmokin; husbands with smoking wives also showed an elevated' risk of ~.Wg cancer, the SMP-s being 1.00, 2.14, and' 2.31 in nonsmoking wives, wives stnokina 1-19 cigarettes. and wives smoking 20 or more cigarettes daily, respec- &ely (P - 0.0177). This observation also strengthens the evidence listed above (Table 6). TABLE I! LL'7rGCAf+CEI MORTALITY It.. WOMENtY. AGEGtOIT AND OY. HCSSAVDS'SMOKINC,HAIIT '(PATIErR HERSELF /Y.NOMSMOKEIIM 6.nd' Wu s Husb.nd t fnakmj lubt s, aK pa+D Nonsmotcr Fauvwker 1-14day 1S-19nday 2D+ +dsy' 7OW q"9 4 •_''9 *1 1.233 1 t.6:1 1 6 9.1!t 16 10.764 3.q 3:.0_7 l0-39 /0 7.791 3 I.92: 20 9.W t 4.oS_ 24 9.t?0 i.t 3)~~" i0.69 at 7.120 1) 2.6/7 32 7.243 9 2.513 23 4.651 0# 24.214 70-79 3 733 2 3" 2 .12 1 105 1 226 11 2M6 Tmaf 37 211.0" 17 0.212 V`x.1aw 24 11.IL'f M 25.461 300 91.sQ TIe sipma otmw est~K of rKe rwb md eew-Euca 90 , 1.00 1.3a~.i I'4'~/.Oi 1!0~`% 1.91<i:7t wM«k e:uin;nn du 2.915 oWGdencc lame. 1.0/ peerail P value 0.00179 Hautd,H.enutl ciu 1.0tS.q 1.t: 90 3.0295 Osc-uil P valiW - 0.1389 0.03 37 0.0012 ' Praspcnrvt sa.udy..1966-1961.:hpan. I-

682 ' T. HIRAYAMA . TABLE 2 LL'NG CAtKER MCRTALITY IN'WOMEv eY AGE GROCI. fY OCCCFATION.,AND tY'HLSRA-4DS' SMOKING HARIT(PATIE!tT HERSELF A NQNSf1OKER1° Husbrnd's smokins habit Husband's Husband's occupRtion OK[roup Nonsmoker Ezunokcr 1-1i9iday `.D* tdRy Total Apicultural 40149 1 2.' ~02 6 5.941 9 3.636 16 12.079 4vorkeT 50-59 4 3.497 16 6.812 9 331,4 29 13:823 60-69' 13 4.064 33 6.843 10 2.152 56 13.08 1 70- 3 323 1 446 0 89 4 u8 Toca1 21 10.406 56 20.044 28 9.391 105 39.841 Other 40-49 3 3,7.7 9 9.093 7 7.1'28 19 19.9i8 70-39 6 4.294 IS 8.830 13 6.306 36 19.430, 60-69 5 3.036 IS SJ98 13 2.499 33 11.133 70- 2 432 4 619 1 1137' 7 1.188 Tota1 16 11.489 43 24.140 36 16.070 95 51.699 The weishtcd point 1.00 94 1 41 < 2.74 1 93 < Mantel extension estimate of rate ntio . 1.0 . 1.35 chi 3.145 and test-based 90% CocMdence limits One•tai P val l ue 0.00083 Mantel-Haenszel chi _ 1.786 3.053 One•tail P value 0.03705 0.00111 • Prvspective study. 1966-1981. Japan. TABLE 3 STOMACH CAVCER.MORTALITY IN WOME!t'./Y AGE GROt7 AVD /Y HUMIANDS' SMOKING HABIT (PATIENT HERSELF A NONSM0KER1"- Hu#xnd's Hutbend'y wroolury habit ye poup Noaaawien Ea.m.)ker I-I4,dey I}-194day 30• day Total 40-J9 31 6.:29' 12' 1_Z7} 44 8.611 23 5.011 itl 10.•6J 1911 3::0J° 10-39 _ 60 7:79I 14 1.92» 82 9.6MI 36 4.05.2 77 9.tt:0 b9 3r.2!t3 60-69 1.1 7:IY1~ !0 2.687 I0v 7:U3 40 :.!13, 78 4.6St, 39e _J.:14 70-79 7 755 4 3i! II 612 1 104 6 2-16 '-9 ~.W6 Total 219 21.895 00 0.217 :.4626.144 Inn 11.R.0 _d9 ~.e.Mli t5+ 91 V0 I.la~G43 1~ 1.17 On~I'-' I 10n l.w ~ ?le ra+ttlned pam 1 ~ Q.93 -'" ~O.n6 . Oa 1 O.b Mamel eslen.ion . esumate or rue chi -0:'_70 e.uo and tesl-bescd Onr•ut l 909F oouGdeece URUts P vsl ue 0:3937i Mamel-Hreaszd ctti 1.0W -0.016 -0.033 0.091 Oseaai! P v.lue - 0:IaN0 0.4936: 0.4RM4 0.4075 ' Rr'aeOecUK WdR J966-1901. Japan.

SYMPOSII:M,: MEDICAL PERSPECTIVES ON PASSIVE SMOKING 683 TABLE 4 STOMACH Cw%K'Ea %10KT',LIT1 ra, wtwE:%aNAGa GROrP. n OCCrPATno'-.a.uai,HrsrAWDS' SVtMi1vG HNIT IP4TIE%-i HERSELE A NOrSWOKERI" Husbrnd's smoking habit ^ Husband's Husband's occupation W irouD Nonsmoker E:srtwler I -19,dati '-D- /dsy Toud Asricuhural Morker Total Other iotal 41-19 30-!9 60-69 70- 40-49 30-59 60-69 70- 13 37 77 3 130 IB 13 44 4 89 2.502 3.497 4.084 323 10.406 3.7:'7 1.294 3.036 /32 I! 1.489 41 5.941 56 6.812 116 6.845 13 +46 2-16 20.04+6 38 9.093 76 8.830 83 5.59R 3 619 .00 24.140 25 3.636 37 3.514 43 2.132 3 89 108 9.341 23 7.128 40 6.306 35 2:199 3 137 101 16.070 79 130 236 19 464 79 139 162 10 390 12.079 13.1123 13.081 858 39:811 19.948 19.430 11.133 1.188 51.699 IB ~ 1.24 Mantel extension The weighted point estimate of rate ratio and test-based 1in lQ < 0.89 1.05{ 0.89 chi fMe-tail 0.234 90% confidence limits P .•alue 0.40749 1ltantel-Haenszel' chi One-tail P value 0.298 0.486 0.3828t 0.31U8 • Prospective uudy: 1966-1981. Japan. ..7._ . •._1• in • a~- ' s. 3f 'I ~ !. • I • itlo:JR . 41o:tre ~ IIW :t s. a.. ~. .~.•. .. .. r».. •.....~.~.:... e..,. .r.•• .• ~......•.. *-.... ... .....-•. Ftc. I. Relative riak% o( lung cancer and'rtnmachcancer in 91.y0 nonsmokin8 wives by liusbandi smokin8 hrMt. tProspective Study. IMM-19M1. Japnn.l

684 1 .. ..•...•. 1 T. HIRAYAMA /uswC'L o9t orp4~ 56 • 59 E7 - I 14 .•n.. •t1 fbrt7111r ' II Gotlc i ~, II ~ ,~ ~• . . a,. FIO. 2. Mortality ratios ror lung cancer and'stomach cancer ia aonsmokin= wives by hucbands• smokins habits. IProspective Stud'y: 1'966-t9811 Japana a1Vasa/ Sinus Cancer r7i A significant risk elevation of cancer of para nasal sinuses in nonsmoking wives ' .vas• observed according to the amount that husbands smoked'~, the SMRs being ILAD. 1.67, 2.02. and 2.55 when husbands were nonsmokers or smokers of YO- 14, IS-19, or 20, or more cigarettes daily, respectively (P - 0:02482) 6Table T)• No othetytisls factors studied were identified as sianificantly altering the rtisk%-Sf' rusal' sines cancer in women. !r a9e C• Itispvms IY tiCC'JI<^tlon Of hM1ttOa`BS' D !i !Y ~n; r I J:. OI :LS* rviut 17r,' ~ ~~~Opp ~Na-n ~ • ow-stmxr:t:e: FIO. 3. Morulity ratios for lung cancer in nonsmoking wives by husbands' snakin= habits. IRco- •pcctivt Study. 1966-1961. Japan. l

SYMPOS1uM: MEDICAL PERSPECTIVES ON' PASS1vE SMOKING 685 TABLE 3 LC^1G CAVCER MORTALITY IthOYSMOY.1vG WtN1EN:RAT10/Y'SELEC7ED R1sll FAcrrxs- / Mortality ratio trtlative nskl Chi-sQuare values H,usband's charsctenstics Smoking 12t1 cig.-Iday) 1.91i 9.18 Drinking 1.06 0.04 Population density! ts00-WJ-600 1.10 0.30 Women-s chanctenstics Occupation: Agriculture/others 0.95 0.17 Number, of children: 0-314-9 1!.09 0.48 Drinking: -I- 1!A. 0.01 Meat: Daily!others 1!. I: 0.09 4itaenryellow vegetable: Dail) others 0.98 0.93 Soybean paste soup: Daily,others I'.08 0.29 • IProspenive study. 1966-1981.1apan. $r~tin Tirmors ` '~he risk of brain tumor was also observed' to increase with an increase in the -tuent of husbands' smoking habits. the risk for nonsmoking women being 1.00. 3.03. 6.25. and' 4.32 when husbands were nonsmokers or smokers of I-14. 15-: ~ -ALor 20 or more cigarettes daily, respectively (P - 0.00376) (Table 8). Cancer of Al'1 Si'rts `.In the case of cancers of all sites. a significant elevation in risk was observed. 'the SMRs for nonsmoking women being 1.00. 1.12. and 1.23 when husbands were aonsmokers, ex-smokers. or smokers of 1-19 or 20 or more cigarettes daily, TABLE 6 LL'NG CANCER MoATAUTY'iV. NOMtNottlNG HIiSBANDS fN ' WIYES' SMOKI!rGIItABiT' sband's H Wife's snwking habit u ase group Nonsmoker 1-191day 20+Iday Total 40-59 24 110.7411 1 321 I 1i4 26 11.246 60L 33 {.l38 3 276 2 229 3d 9.043 Total $7 19 ±79 L_ 99'f `3 413 st 20'89 The treiShted point estimatt ti3 2 ~4-9r 31 e{f rate ratio and'test-based 1.00 2.1 0.9d "0.90 IHantel extension 90% eonfidence limits t:hi 1.989' 1.00 ~=3<1.19 One-tall P value 0.02333 Mantel-Haenazei chi 2.1046 Otm-uillP value 0.0177 ' Prospective stud). 1966-1981. layan:

686 T. HIRAYAMA TABLE 7 NASAL SI!tLS CANCEA MORTALITY'INWOMEV.I1'. AGE GROUP AND~/v HLSilkVDS, SMDKING HAtlIT (PATTEYT~ HERSELF A NONS.MOK£Rr Husbend's sawling habit Husband's a0e poup Nonsaakcr Ea•cnwher I-It+day 1!'-19•diy =0- day Toul 40-49 70-59 60-69 70=79 Total 0 1 J 0 5 6.229 7.791 7.120 735 21'.093 0 0 0 0 0 1.`^'tS 1.92-1 2.687 , 34E 6»11 1 2.621 3 9.660 5 7:/3 0 612 9 ~6.lat 1 3.1911. 1 4.032 2 2.313 ' 0 103 4 Il.t-2t 2 10.764 2 9.100 6 t.639' 0 1-16 10 .3.t61 4 ' 7 17 0 :E 31:0•7. 33,..!3 .e.]l4 2.0.6 91..W The weet;hted poant 00 1 1.67 t.'0 ~ 20: 33 ~ LSa 6.:7 < esmtatr of nte . 0:67 .M 1'.Ot ldanuleaen.wn two a.d Iea-baed chn 1,90,31 90% caeridence One-tail ba!l17. Mrttel-Flaenassl cAi 0.916 1.012 1.713 P value 0.0:at_ Ope-taii r rtiue ~ ~ 0:17l3 0.1J5r 0 0a336 Nore. 1n eanpwauon. s6es ti0-69 and 7D-79 .e+s oomt>.eed. • Prvspecuvc study: 19b6-1991. Japan. respectively (P - 0.00020) (Table 9). `Th3s risk elevation is influenced by the -'e~levated risk oflunQ cancer and'cancen of other selected sites such as`nasal tnus tancer, brain tumor, and possibly also breast uncer. Risk elevation for cancer of all sites becomes nonsignificant when these cancers are excluded. No sieniticant association was observed with other cancers such as those of the mouth. pharynx. esophagus. stomach, colon. rectum, l!iver, pancreas. perito- neum. cervi'x, ovary. urinary bladder. skin, bone, malignant lymphoma. or leu- TABLE 6 BKAIV TLaIOR.MoRTAUTY.1v WOMEw. Oy AGE GROt.'P AND OYHLf6AVDS' SMOKI*G HAlIT (PwT1EYT HERSELF A NO*tSMOKER)' Husbandl smo6in0 habit INYfbend's a{e Sroup Numnwkcr Ea-smoler I-li day 1!-19Aa> -0- di> Total 40-49 0 6'»"9 0 L:.45 1 8.01,21 6 3.156 4 10!76•4 II 32.0_'7 50-59 I 7.791 0 1.922 + 9.61,! 3 J:03] i 9,R_0 12 33,Z<3 60-69 1 7.L0 0 2.6K7 t 7.2133 0 :!13 A 4.65 1 10 24.214 70-79 1 $5 0 34111 0 612 0 1ot 0 22'6 I 2.0A6 ToWal 3 :1.1" 0 6.212 10 311.I++ 9 1r.1R.`I 12 21C.461 34 91..L0 Theaw~nfea~f rae t 1.00 ~ 3A3~1~ 6._<<19.01 t'3'~.1.53 Mantel extensan ratio aed teu-b.red ch 2.671 1110% eaKiOt:eee One-tail lisu4a P •aliu 0.0076 Watel-Hatastoel ehi 1?!6 2.6!6 1.317 Oee.tyl P.alue - - 0.0954 0.00)95 0.010.3 Nwe. IK can0utauon. -Oes 60-69 and 70-79 "sre a>atbtned: • Prospeai.e stn0y. 1966-19f1. Japan.

SYMPOSIUM: MEDICAL PEASPECTIVES ON PASSIVE SMOKING 687 TABLE 9 ALl SRFS CA4C'Et MOaTAUTI t% woME-4 aN AGE GnOCR BY OCCCtt4Tto%-: ASD at' HLSY.aNDS* SL01:IVG H.tY1T IPATIExT HEMSELi A VOVS4(b;Eal" Husband~s stnoking habit. I Husband*s Husband`s occupation aie tro.+p I:onsmolier, F1ttn0kYr I-19,day , 20-ida} Totaf. Apicultural worker Tocal Other otal 40+-49 30-59 60-69 70- 40-49 1.0-t9, 60-69 70- 40 96 .03 17 358 48 79 13: 17 276 :.50: 3.497 4.0lCk 323 1'0.406 3.727 4.?9a 3.0z6 432 11.489 119 5.941 201 6.812 37z 6.lU S L' 446 715 220.044 1'1'8 9.093 248 R.R?0 239 5.5" 21 619 626 24.140 76 115 1.7, 5 323 103 169 1:9 6 s07 3.636 11.514 2.152 89 9.391 7,1:8 6.z0b :.499 137, 16.070 235 412 705 44 1.3% '.b9 496 300 44 1'.309 12.079 13.8'_3 13.081 1s8 39.841'. 19.948 19.430 11.133 1.IE8 51.699 The weighted point 1.00 1 1.12 < 1.2 1:_z ~ 1•;t .03 1 1 .1. Mantel'extension estitrute of rate ratio chi 3.50) and test-based 90%, 1 coafidcnce limits One-tail P value 0.000=0 Mantel-Haenszel chi _ 2.232 3.628 One-tail P value 0.01281: 0.0001s. • Prospectivr study.,1%6-1981.,Japan. temia. the direction of this trend being evenly distributed to both the plus-side (risk increases with the extent of husband's smoking habit) and the minus-side (risk decreases with the extent of husband`s smoking habit). DISCUSSION This study confirms the correlation between lung cancer and spousal smoking reported previously: The correlation is quite specific in terms of diseases. For instance, no risk elevation at all was observed for stomach cancer. A striking interttal' consistency of association was also observed. The results were essen- tially similar when: observed in terms of age of husbands, age of wives, occupationn of husbands, and differing periods of observation. The results are in fne with a Greek study by Trichopoulos and others (10) and a U.S. study by Corrsa and others (4); (external consistency), although they art slighzly' at variance with an American Cancer Society study in the United States (S) and a case-control stud'y conducted by Kabat and Wynder (8). Differences in proximity between husband and wife in daily life, room size,. room ventilation, and frequency of wives who work in offsces in these countries are potentially influential factors in enhancing the extent of risk posed by hus- bands' smoking.

688 T. HIRAYAMA Histology of 21 cases of lung cancer in nonsmoking wives with smoking hus- bands was not essentially different from that of smoking women (adenocarci- noma. 57.1%; squamous cell carcinoma. 19.0~7c; and small-cell carcinoma. 4.8%). ~LThe current results of elevated risk of nasal sinus cancer in addition to the risk of lung cancer must strengthen the plausibility of carcinogenic hazards of,•- sidestream smoke inhalation through the nose. as they are in line withh the results of measurements of various carcinogens in sidestream smoke showing them to be present in higher concentrations than in mainstream smoke (2. 3). These results are also compatible with known evidence showing a possible influence of passive smoking on health including elevation of carboxyhemoglobin and nicotine/co- tinine levets in saliva. blood', and urine after exposure to passive smoking: ele- vation of hydroxyproline levels in urine (a marker of collagen destruction in lung tissue); the presence of mutagens in urine ( I); small airway dysfunction in those exposed daily to passive smoking in the workplace (T I): and risk elevation for pneumonia. bronchitis. and asthma in children with smoking parent(s). When the effects of passive smoking due to husbands' smoking were compared with the effects of direct smoking in women, the results clearly indicated that the effect of passive smoking is less than one-fifth that of direct smoking. the SMRs being 1.55 and 3.81. respectively. In terms of attributable risk. however. the effectt of passive smoking on lung cancer in women is nearly as important as that of direct smoking because the population of intrahousehold passive smokers at risk is four times greater (rr - 69,645) than the population of active smokers (rt = 17.366). Therefore, although the relative risk of indirect smoking is much smaller than that of direct smoking. the absolute excess deaths from lung cancer due to passive smoking may be quite important because of the large size of the exposed group-especially in countries such as Japan where the majority Inearly 70170 of adult men smoke, but only a minority (1S% or less) of adult women smoke. Passive smoking can be divided into (a) direct passive smoking (direct inhala- tion of sidestream smoke before being diluted by room air) and bb) indirect passive smoking (inhalation of room air polluted by sidestrearn smoke) according to the extent of proximity effect. just as droplet infection is sepanted' from droplet nuclei infection in acute respiratory communicable diseases: the effect of venti- lation is of limited importance in the former case. although quite significant in the latter. Small room size and congested living conditions in Japan (and possibly also in countries like Greece) are naturally more conducive to direct passive smoking. As described in a previous report. the age-adjusted mortality rates for lung cancer are increasing rapidly for both men and women in Japan. As only.a fraction of Japanese women with lung cancer smoke cigarettes. the reasons why their mortality from lung cancer nearly parallels that of men have been unclear. The current study attempts to explain at least a part of this long-standing riddle. Although the average rate of female smokers in Japan has remained fairly stable over the past 20 years. a statistically significant increase in the mortality rate for lung cancer in nonsmoking women was observed in our long-term follow-up study of a large-size population. Mortality rates per 100.000 for ages 50-59. 60-69. and 70 and above were 7.1. 17:7. and 31.0 in first 10 years of follow-up and 9.9. 27.1.

SYMPOSIUM: MEDICAL PERSPECTiVES ON' PASStVE SMOKING 689 and 44.3 in the subsequent 6 years. respectiwely (P = 0.00373). This phenomenon can be interpreued as the influence of widespread exposure to passive smoking in Japan.. As also emphasized in this earlier report. these observations strongly question the validity of the conventional method of assessing the relative risk of developing Nurtg cancer in smokers by comparing it with nonsmokers. This study shows that nonsmokers are definitely not a homogenous group and should be subdivided according to the extent of previous exposure to indirect or passive smoking. The observation of the effect of passive and active smoking on lung cancer risk in men and women revealed a similar effect of both active and passive smoking onn lung cancer whew nonsmokers without exposure to intrahousehold passive smoking were used as the unit risk group (Fig. 4). - The observation of an elevated risk of brain tumors in nonsmoking women witti tmoking husbands is of importance in considering the etiology of brain tumors (an area in which our current knowledge is quite limited),, especially in relation to a similar report on the influence of passive smoking on childhood brain tu- mot49). 9.0 8.0 7.0 6.0 s.o ..0 3.0 st..rrsrns Ot41 Tr YT10 2.0 1.0 0 I j % % % i W amUi 1111017 a N f 1•N/MlF/11 tr &~, r w st' wst't ..cls r.~• W It Ws~~1 ~ W.~.M a[ATw !/ M 46/ /~ IN~ Hl7 tWaAtlM f ~T.yM»M r~M7f ~yi1~ M L WryM~y I/rt1~wµ • ~.....~. rr...~ ~. ~-..r•. Fic. 4. Active and passibe smokirl0 and IunO qncer mortality: Relatire tisks (RRI vvitH 90% con- fidence imervals. (Prospective Study. 1966-196t. Japan.l