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Table 7a. Mortality rates for major cancers other than lung in women by age group and by smoking habit of husband (patient herself a nonsmoker): peospective atudy, 19fi6- 1981,Japan• Ho.baod's age tro"P 40-49 S0•59 60-69 70-79 Total Hn.baed't .e.okiag Babit (tigarette a daF) 121-.eoker - No.soker 1-19 "+ Total No. lop. No. Fop. Na Pop. No. Pop. 44 97 160 14 313 6.229 7,791 7,120 755 21,895 117 1:91 274 20 602 15,034 15.642 12.443 1.06s 44,964 71 119 306 a 304 10,764 9,820 4,651 226 25,461 232 32,027 407 33,253 540 24•214 42 2.046 i,221 91,3401 . QIl 1.00 1.00 1.00 1:00 0.90 0.95 Mand eaea:oe y~ 0.113 _ -o.00tS 0.0149 .er~ai 0.4994 0.4621 ~.Yre 0.4542 Table 7 b. Mortality rates for major cancer4 other than lung in women by age, occupa- tion, and imoking habit of the hu.band' (patient herselC a nonsmokcrr Hwbbaad. Ia-emokar age Nos.moker o.1-19/da~ Z20/day (peare) Occrpation" N.. Pop. No. Pop. No. Pop. 40-49 Total 45 6,229 120 15,034 74 10,764 1 2 324 1 653 3 566 2 90 1 231 2 293 3 9 908 17 2,247 12 1,867 4 3 476 • 993 8 1,044 S 17 2,502 59 5,941 35 3,636 6 46 165 106 7 1 177 6 486 426 • 10 1,112 21 3,431 13 2,241 9 1 162 4 345 1 243 10 2 432 3 542 340 • 50-59 Total 98 7,791 195 15,642 122 9,t20 1 13 345 2 393 3 446 2 2 175 1 253 11 319 3 14 817 16 1,764 10 1,324 4 1 .653 td 1,133 9 1,092 5 49 3.497 111 6,612' 56 3,514 6 35 89 50 7 2 120 4 273 2 234 • 12 1,375 49 3,478 31 2,155 9 164 7 378 4 251 10 3 610 17 669 6 435 60-69 Total 161 7,120 227 12,443 106 4,631 1 5 227 5 327 2 179 2 5 91 3 143 3 124 3 7 303 11 594 5 327 4 3 50o 28 !22 12 500 5 102 4,084 158 6,645 58 2,152

156 TdcesN 'wcryarno Table 716. (ooot.) Hu.baod. Za-,moler ar 18oo.ooker .r 1-19Jday t 20/day. Q7sar*) Oecupaioa6 No. Pop. No. Pop. No. rop. 6 9 1 31 ' L4 7 1 ` 45 3 02 2 55 e 10 003 40 1.784 17 736 9 2 121 3 208 92 10 24 925 25 1,607 7 472 70. Taal 14 755 21 1.065 t 226 1 32 3o s 2 1 21 14 G t 3 1 18 36 B 4 48 1 73 2 20, 5 7 323 35 446 4 69 6 1 1 0 7 1 • 5 1 • 1 87 2 119 1 36 9 11 39 2 10 4 213 3 322 1 61 • Sundaediami lli.k Rrnc. 1.000 0.969 1.034 r lifmd matuion ZI: -0:129; onrfaJ.y r.lut: 0.f4866. 60erupaice: I!. Trok..owa, .nd tedtnicaiwortiesa: 2. mana6m and olficuiaF.; 3. derical and ndued .orken:,4. rki .ortrn: 5.,hrtnfn. lumbennen. and fi.hertnen: 6..rorken in minint and quarrying oreu.pumna: 7:.vrirn e v.n.port aod.oummunicrionorcupnion.; l.rnkamen, p.odunion.pwca .orien.,and lalarn.: 9. tt+viee .orien:.10. aa.darifiablc and ua reponed. Comparison of the Effects of Active Smokine and Passive Smokin0 •aVNhen thrriak of lung cancer in nonsmokers with nonsmoking spouses was takti I" anit, a definite dose-response relationship was observed;, the highest IDeuig i1y heavy active srnokers; followed b~+'m~d active smokers, then heav~piuive anokers, and then taild' passive smokers (Figure 7). The risk gradient was sitnilir both in men and in vMomen (Figure 8) "A stgnt6cantly Ekvated rtsli'of lung can"cre°>i ~ ab~' was ~ttited for lsonsnng hiss~ali~'i with"amoking wivi. .` Because the size of population exposed to passive smoking is quite large in the eax of women; the effect of passive smoking because of the husband's smoking was estimated u 6596 of that of active smoking. Our recent survey showed that 47.,5% and 32.6% of Japanese adult women were being exposed to passive smoking at home and' at the workplace, respectively (Figure 9). Thereforr it must be a sound estimate that the total effect of passive smoking is approximately equivalent to that of active smoking in women. However, as a majority of adult men are still smokers, the total effect of passive smoking relative to active smoking must be on • r 0 .

l.txnp Cot+cer !n .lapcxt Norttbn and Passive Srnohlnp 187 v.0 s.0 34.0 II.0 10.0 L0 i.t t/MY/llQl rM~ t.~ 1 T Yl lo 4.0 ~.0 1.0 LI_ 0. //Fir wlr H/I~S.LMIf •YII Y. I II~ti t~l~~f IOrr 0 m r w 4. , t! i1 1. ' I/It 1*w... r Wr t . M 1. r rt+.' r• tt a sr r n n n w q. M. Mp e 11 r1iT r/F 7try•tl„ rMt rat MM. u11 Ifw.. MM tUl !M r. r • 1. r« 1. riw w .• M t CM/ItttlI t./llnft . . •~ r.w .r. .~. . w... ~.. 1. r.t.. .« u.+. ... r.w (b) e.0 •.0 6.0 7.0 S,0 ..0 1.0 tT-OY9I aDptY1R Yt 10 z.0 1.0 MrM~~IM.: ur / r l./~ tp D~~ M _ Y In /t IIAI. Y/Y nMt IYM. 17M I.w t.tl ..u~ f. R Lq r.n. I:.tl. /~n {.~~ 1',M Ln 1.11 ~ 1.M - _la." ..w..wl - - w•~..w.. Figure 7. (a) Active and passive smoking and lung cancer mortality: relative risks (RR) with 9096 confidence intervals; males.(Prospective study, 1966-1981, Japan.) (b) Active and' passive smoking and lung cancer mortality: relative risks (RR) with 90% 'confdence inter vab; females. (Prospective study, 1:9G6r1981', Japan.)I the order of a few percent. The effect on lung cancer risk of passive smoking at home in reiation to active smoking for men was calcvlated as 0.4% in our series. Effect of Nutrifiion on Passive Smokers A significantly lower risk of lung cancer was observed when nonsmoking wives with smoking husbands consumed green-yellow vegetables daily (Tables 8 and 9, Figures 10 and 11) suggesting that the promoter-inhibitor interaction model also ~ applied to passive xnoking just as in active smoking (Figure 9). Such risk reduction caused by daily intake of green-yellow vegetables was not observed for isc2ietnic hean disease (Table 10, Figure 12). s

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Table 8. Lung cancer monality rate in nonsmoking wives by smoking habit of the husband: compariavn be- twccn daily and non daily intake of green-yellow vcgetablea . Husband's E.z.nwker rtakinR habiu Noocmoker on 1-19 day 2 20/daj Wife's eating habits Grcc.-ycllo. .c{ct ablc. Daily Nondaily Daily Nondaily Daily _ Noadauy Lusg Lung Lung Lung Lung Lung Husband's Pop. Ca. Pop. Ca. Pop. Ca. Pop. Ca. Pop. Ca. rop. Ca. Occupatloa Age Agriculture 40-49 1,958 1 S44 0 5,050 S 891 1 7,037 7 S99 2 50-59 2,805 4 692 0 5,196 II 1,616 S 2,588 9 926 0 ~ 60-69 3,359 7 725 6 3,106 22 1,739 11 1,588 6 564 4 70-79 258 3 65 0 287 1 1S9 0 43 0 44 0 Othen 40-49 2.422 3 1,305 0 7,286 8 1,803 1 5,377 3 1,731 2 50-.59 3.181 5 1,117 1 6,732 12 2,098 3 4,633 S 1,673 10 60-69 2,266 4 770 1 4,08a 9 1.510 6 1,906 10 S9S 3 70-79 216 2 216 0 371 1 248 3 8 1 1 56 0 Total 16,465 29 3,430 ! 74,118 69 10,066 30 19,25! 43 6,206 21 Graad totd Populatios: 91340 Luag ca.cert 200 Green-yellow rt8etabla Mantcl-utencion x3 P-value (two taJed) Daily 2.072 0.0)827 Nondai_ly 2.487 0.01288 Total 3.090 0.00200 • I I I tISIzeCL-0 ~~

190 Taketfli Hit>~otr Table 9. Eiect of daily intake of gmn-yeliow vegetables on lung cuscer monality in eronsmoking wives with tmoking husband!• Htuband't !s-rmoker mooking habil or 1-19/day wifi'relieg 6.bil Z.nng Lamt Lung Lung Htu6ved's Top. ca. Top. ca. Pop. ca. rop. ca. Occupation Age Agricultu+r 40-49 5,050 5 891 1 3.037 7 559 2 IF 50-59 5,196 11 1,616 5 2,588 9 926 0 60-69 70-79 5,106 287 22 1 1,739 159 11 0 1,588 45 6 0 564 44 4 0 Otben 40-49 7,288 8 1,905 1 5,377 5 1•751 2 50-59 6,732 12 2.098 3 4,633 S 1.673 10 60-69 4,088 9 1.510 6 1,906 10 593 3 70-79 371 1 248 3 !1 1 56 0 Total 34,118 69 10,066 30 19,255 43 6,206 21 'lfamd•Haread 7t': - I.W. P(t.vuikd 0.047);Odd/ rrio:Noedsi}yPiT^-1'ego+veZetaEk rlaier.1.000: dailr pees-ydb" .egelabks iwukr.0.707 (wardardued rre rrio); 90% caefidcnee iimrs. 0.53-0.943: i Nw~a•t~llw y`NldtawNY 01 N~~WI~~ tW.y11M~. rnt t.a1 4.93477 - oiwn>:.y> 4.912M Figure 10. Lung cancer morulity ratio in nonatnoking wives by ctwking habits of their W husbands. Comparison between daily and nondaily intake of green-ydlow vegetables. . • . . ~n - l n - V t :20/day ct--yea-. -gt.w« Dailr ' BToodal7y Daily lioedaily

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. A I Table 10. iahemic heart diaease monaiity rate in non.mokins wiva by .mokins habit or the hurband: com- parison between green-yellow vegetabies intake daily and nondaily Hueband'. Ls-..okee srooking habit None.roker or 1-19/day t2ll/day Geeeo-ytno.r .eTet.blee Wite's eding habit Daily Nondally Daily Noaddly D.IIy Nondaily Huebaad'. lechnwk 1.chemic Pop. Heart D. PoP, Heart D. I.cheoie Pop. Heart D. labesle PoP. Heart D. l.cbewk I.cbesk Pep. Heart D. Pop. Heaet D. Occvpaloa A6e ~ Aarkdtute 40-49 1,935 6 544 2 5,050 16 691 7 3,037 14 399 S0-S9 2,80!1 11 692 4 l,196 23 1,616 2 2,586 21 926 1 60-69 3,359 30 725 6 3,106 SS 1,779 24 1,568 21 564 6 70-79 258 2 65 3 287 10 159 1 45 2 44 0 Ovhers 10-49 2,422 3 1,70! 2 7.208 10 1,805 5 5,777 12 1.751 9 . S0-S9 3.181 6 1,113 3 6,732 16 2,099 11 4.633 17 1,673 6 I 60-69 2,266 21 770 6 4,098 33 1,510 13 1,906 11 . 593 9 ~ 70-79 216 7 216 2 371 6 248 2 61 3 56 2 Total 16.465 e6 5.430 30 74,118 175 10,066 63 19,253 101 6.206 35 Gtaad tot.l Popalaios: 91540 leche.k heart dl.c..a 491 Orcen•yellow veRetables Mantdt:neniion x1 P value (two tai{ed) Daily 2.307 0.02105 Nondaily 0.820 0.41222 Total 2.406 0.01613 ~./S f+s'jC7 li Ci Cya~(.a

lynp Carlce.ln ,10porx NuMrlm ard iosah+ Srrlddn0 193 ..u.N•s s..a.. ..., { tn..• {f 11" fftft'{Mli• •INI{ 1... 1.00 ... fMi.I ONI.I-t{t.Ffl.. C./. ~ .~Iff tt..-t1'.11f~). i1Of •.l3~ f.Ylii! Figure 12. [xhemic heart diseax mortality ratio in nonsmoking wives by smoking tiakiits of their husbandi. Compsrison between daily and nondaily intake of green-yellaw vegetables . DiscWsslon The age-adjusted mortality rates for lung cancer have been sharply incttasing both for men and for women in Japan. As only a fraction of Japanese women witli. lung cancer smoke cigarettes, the reasons for the trend of their mortality from lung cancer have been unclear. The present study appears to explain at least a part of this long-standing riddle. TTiis observation alw questions the validity of the conventional method of assess- ing the relative risk of developing lung cancer in smokers by comparing them with nonsmokers. Thiu study shows that nonsmokers are nor a homogeneous group and should be subdivided according to the extent of previous exposure to indirect or passive smoking. Although the relative risk of indirect smoking was smaller than that of direct smoking, the absolute excess deaths from lung cancer resulting from passive smoking must be important because of the large size of the exposed group. Therefore, these results of our current study must be of public health importance, strengthening already existing evidence (or a health hazard from passive smoking (11-13) (Table 11). As shown in Fgute 9, 47.5% and 32.6%, of 158 nonsmoking adult women surveyed recently are noted to be exposed to sidestream smoke at home and at the workplace, respectively. One sutvey conducted in Aichi prefecture in Japan showed that nonsmoking wives are exposed to their husband's smoking,6.7 times a day on the average. Because sidestrearn smoke contains .•arieties of cancer psomoten at higher rnn- ~entration than does mainstream srtsoke, it must be raasonalble to consider the s

194 TokasN Htayamo Table i 1. Passive srnoking is hariardous to health 1. Existence of tmtit: .ubseu+ces (indudin6 cawunoaesu) in .idatrcarn smoke eoo.Jy a bi3her coeKan- trauon than at mainstrcarn otwkr. 2. IJCiarna of a large numbcr of nonmwken rrho A.ve to uJiak idatrram WDokr 6equendy .nd in- tensivdy for long yttirs at htmtr and/or at the workplace. 3. Existence of odcurrsm .moke component iq blood and tuine of nonamoken ocpoxd to pa.ove wnokin`. (e6, nirntine. (?p.Hb in hiood'and Mutasens in urine.). 4. Existence o( (unctiona) abnormaiities in eonanokers espo.ed btwily to pua`"r .noicing (eg. eraptrxory or dreulatory function). S. Lun` tuwe damage and destruction in ehronic p.ssivt snoken as ahown,by ekvated byda•wry. protine excretion in urine. 6. Highet, incidence of selected d'iseaaes in nonnn*as expoaed heavily to passive .noking (eg. pneumrnua, bronchitis, aulima. i.chcmic Ae.rt disease. lung and nasal sinus eancrf). • 7. Fxperienental eridence. -4tain etfect of passive smoking on lung cancer risk results frosn the prolonged ex- hitosure to such promoters in sidestream smoke.'Ile risk-inhibitory effect of a daily intake of green-yellow vegetables that are rich in S-caroaene must be considered as an additional evidence for such a promoter action hypothesis of passive smoking. The hypothesis also explains why exposure to passive smoking that starts afier reaching adult age can significantly influence the risk of lung cancer. TZte histology of 21 cases of lung cancer in nonsmoking wives of smoking husbands was not essentially different from that in smoking women (sdenocar- einorna 57.196, quamous cellcsrcinoma 19'.0°,b, and'small-cell carcinoma 4.8°k): A case-control study conducted' within our cohort study revealed a significant dose-response relationship between adenocarcinoma of the lung and the number of cigarettes smoked daily,, relative risk being 1.39 and 5.75 for smokers of 1-14 and 15 or more cigarettes daily, the chi'square for the trend being 6.848 with a one-tail p value of 0.004. Therefore the predominance of adcnocartinoma of the lung in nonsmoking women with smoking husbands should not be considered unfavorable evidence for promoter action hypothesis of passive smoking. In passive smoking, sidestttam smoke usually is inhaled' through the nose, whereas in active smoking, mainseream smoke always is inhaled through the mouth. This ditTerence could be a reason for the eievated' risk of nasal sinus cancer in passive smokers. The mechanism of the action of passive smoking on the risk of isc}semic heart disease, however, must be explained in different ways (eg, a combined action of carbon monoxide and nicotine). In summary, to reduce the effect of active and passive smoking and to encourage the effect of nutrition, in particular A-carotene intake, would be the most produc- tive course for lung cancer prevention. For sekcted persons exposed to other known carcinogens, eg„those related to occupation or radiation, such envifonmen, ta1 exposure also must be minimized in addition to the preventive measures focused' on lifcstyle variables given above. ~ ra References • n 1. Hifayama T. Prospectire ftudiea on cancer epidtmidoay bwud on census population in )apan. ~ ln: Bucalossi P. Veronesi U and Caueinelli N; eda. Pnoceedin6a nf the XLth intetnational cancer 4RJ Cr~ I t t