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( ~ .,Y). fRITISH MEDICAL JOURNAL VOLUME 282 17 JANUARY 1981 193 PAPERS AND SHORT REPORTS NOTICE This matsrisl may be prstsct:d by cp;,;!j'tt bw (fiW 12, JS. Non-smoking wives of heavy smokers have a higher risk of lung cancer: a study from Japan TAKESHI HIRAYAMA Abstract in a study in 29 health eentre districts in Japan 91 540 non-smoking wives aged 40 and above were followed up for 14 years (1966-79), and standardised mortality rates for lung cancer were assessed according to the smoking habits of their husbands. Wives of heavy smokers were found to bave a higher risk of developing lung cancer and a dose-response relatioa was observed. The relation between the husband's smoking and the wife's risk of developing lung cancer showed' a simi'lar pattern when analysed by age and occupation of the husband. The risk was particnlarl'y great in agricultural families when the husbands were aged 40-59 at enrolment. The husbands` smoking habit did not affect their wives' risk of dying from other disease such as stomach cancer, cervical cancer, and ischaemic heart disease. The risk of develop- ing emphysema and asthma seemed to be higher in non- smoking wives of heavy smokers but the eBect was not statistically significant. The husband's drinking habit seemed to have so eseet ovn any causes of death in their wives, including lung can ccr., These results indicate the possible importaace of passive or indirect smoking as one of the ausal factors of lung cancer. They also appear to explain the long- st.nding riddle of why many women develop lung cancer although they themselves are non-ssssokets. These tesults also cast doubt on the practice of assessing the relative risk of developing lung cancer In smokers by comparing them with non-smokers. be studied thoroughly bentue the side-stream and second- hand smoke of cigarettes contain various toxic substances, including carcinogcns.' ' The need for such a study increased by the report of small-airways dysfunction in non-smokers chronically exposed to tobacco smoke.' The effect of passive smoking on lung cancer was studied by following 91 540 non-smoking housewives aged 40 and above and measuring their risk of d'eveloping lung cancer according to the smoking habits of their husbands. Methods To study the ecnsequenc.+s to health of such factors as cigarette smoking, alcohol drinking. occupation4 and marital status, a pro- spective population stwli• has bccn in progress in 29 hcalth ecntre districts in :ix prefectures in Japan since the autumn of 1965. In total! 265 118 adults (122 261 mcn and 142 857 xortten) a4ed'40 years and ovar, 91-99"„ of the census pupul4tion, were interviewed and followed by esublishin` a record Linkage system betwcen the nsk-faaor rceords, a residence Jist obtaincd by special yearly census, and death ecrtitistcs. Since the effect of direct smoking of cigarettes in this study has alreadVb.en rrportcJ! r my study focvsed on the e&rt of husband!s sctokin` on the risk of lung cancer in their noo-amokina M ives. Such obscn-stion was pouiblc since .ictail.d questions about hfrstyle, including smoking habits, wvrv ask.d of husbands and wives inJ.yen- deatly at the start of this study. No subjrctivr bias was therefore cooccnnblc. A total of 346 deaths from lung cancer in women were recorded ~ during 14 years of follow-up (1966-79): Of these women 245 wcre O married, and 174 of th. sc were also non-gmokers. These cases occurred 7. among 91 54D non-smoking married women whose husbands' tmoking s~ habits were studicd'. The risk of lung cancer was earelully measured, ~ taking into consideration possible confounding variables. w, Introduction , The possible consequences to the health of rsoa-smokers of long-term exposure to cigarette smoke (passive smoking) should National Gaaeer l.entre Ressarch lastituu, Tdtyo TAKE SH'J' H IRAYAMA „sw, strn, chicf of epidmtio7ogy division ~ Results ~ 'Wives of heavy smokers were found to have a higher risk ofdevelop- ~ y istglun=raneerthaswivesofnoo-smoketsandastatisticallysisnifican sVt dose-response rclationship wss observed (Jviantcl-rnension y test ~ result being 3 299; two-tailed p-000097). Age-occupation standud- iseJ annual!mortality ntcs for luns cancer were 8 7/100 000 (32 out of 21 895);when husbands were non-smokcrs or occasional smoken,.

184 14 'n (Rn out of 44 IR•t)', w'hcm hushinds trcrc ca-smokcrs or daiK smokers ef 1-IQ cigarettcs, and I8' 1(56 out of 25 l46)whcn husbands were dtill• cmok'crs of 20 or more cigarcttos. Thnsc figures pve risk rotios of I'00, I 6l. and 2-08 resp'ecti.•cly. A similar trend was ob- served in agc and occupation groups of hushands (table 1). XMs s-Staod..lhed aeenalirr fw hatg emco in a•nrnew 8r age, ampr.eiw, awJ tnttnAi'rpr Aabir rrf the AmbnaJ (ptinu Arcrx(/ d arw,awutrer) Hmband's+anntina habit:; )'Am,mx+ter Es-smober era-l9,day ;~-20iday. f a-ir s' l N. Pt HraMrnf'a qr:.40-Sf 3ran 1 020 30 676 t4 0 at n a e qu 4 NorfieatM6mn8..~caeett 1t 40 2 S 36 Oecupat r nn-sundsad+aed sonahry,1a0lt0 !6l' lilria.rlr Kr.• `-tQ parr 939 13-14 i•ort,l.rinn nf w;,Kt n7s 13 soa 487? NoMdenh.hmmlunao.t:f: 21 16 20 Uccupat r nn..ata ndardistl/ 1rr.nalm ; 100000 1579 2444 29.60: faaMardiacd ma rrtih Ae all traes 1,00 1'41 tps HvJrnltswkeritf r+ qm »hrrrr Populaumqnf.ire+ 10406. 20n14 9)91 Nonf.dcath% fn.mlungcancer 17 52 24' Aae-+tandardi.cd mawtalny r 100 000 9-Si. 17•02 1840 H.ulu.d.w#ina e1.rtrMrre Populatlon o6-e+11 469 24 140 16 070 No.nldtarhafromlunaoncer 1S 34 32 AR-standard,ccJ tnnnalny In0000 913 K.4h 1771! Srandardrsedrfsk'tatYafafallK[HfaLLRS I'W 1,43 1~'90 The relation between the husband's smoking habit and the wifc's risk of det•eloping lung cancer was panieularlcy significant in agri- cultural families when the husband was agcd 4D-59 at enrolment (Mantc4catcnsion chi being 2 597 or iwo-tailcd p=(t009A);; lung cancer 64 rat ios were 1 00, 3' 17, and 4 57' w hcn husbands were non-amokera or occasional smokers, cx-smokcrs or smokers of 1-19 eigarcttcs daily, and smokers of 20 or more cigarettes dailyy respectivth (table 11). TAaLL I1r.Nen7alrry fnr. faV [anCrrin anCmrn by aeCMDatrrnr arad by rwlaRrllI 4abu of 4ar rbond arrtrqr.en aged 40-59 (parrent lrrrulf a won-nwnbrr) Husband'ssrnnkinghabit: Non-etnoker fu-rmnler oelrl9idsy. :.3oiday Attrlculturalrnrkcn: . P.tiwlannnrf wrrn~ S 999 12753 7150 No nf denh, frnm luna cancer . 3 .20 16 Monasay.100 o0n pther..wlera Y4a 11,43 15 92 Prqulatinn ef w'irn 11021 17023 13 434 No of deat hs. (r.rn W ea tasseer a 20 20 Martallty' 100 000 7-15 a-0'9 11-05 ftandardiaednekratiofor.dleoevpitis.s 1-00, 1-07 2-36 The husbands' smoking habits secmed to have no effcct on their .rives: risk of developing other msjor cancers, such as cancers of the stomach (n- 716) and of the ecrs-ia (n=25f1) or ischaemie heart disease (n=406): The risk of developing emphysema and asthma seemed to Nc higher among the non-smoking wircK of smokers. but the effect was notstatisticalh• significant (tablu I 1I N: Othcr charactcrii.tics of the husbands, such as their alcohol drinking habits did'not affxomortality from lung cancer in thcir..ircs. 7'he relative risk ratios of death frpm lung cancer were I'(tn. I 13,,and 1-18 (p-t139h) respectively w•h:n hushands wcrc non-drinkcrs, occasional or nre drinkcn, and daile drinkcn. Similar results were found with other eauses of death (tah)c IV). Finally, the eficct of passive srnoking was compared with thc cffcct of direct stttoking. The cffcct of passiir smoking was around onc-half to one-third than of direct smoking. The relative risk of developing lung cancer by passitr smoking was about I•A compared with about 3'g in direct smokers (fig 1), 6RITISH fwtEDICAL lOt'RNAL VOLL'ME 2R2 17 IAN't:ARY1951 TAaL1 tul-Arr•ncnq,.trron rrandardrred'ru4 nonn fnr ulcrtrd cmura of drorh nt mntn ba^ anrobrayt Aabrr ftft/te Arc•b'and ( Ivr rrnr Arrrr/f a non- rn,nkn ): Caute nU death Hurband's.rnNcmR. haba n Nnn-tmoker Ea-armJtrr, oe 1-19.day. •20 di,y Pvalue Lunacanrcrln, 174~ t 00W 1 61 208 o oot kInpM7ema, asthrna ln 1 66` 1,00' 129 149 0474 CGncct of ccma in ~ 25PI 1',~00 1 1S. 1 14 . 0 2'.49 Stnmaeh eaneer tn ~ 716 , loo 1'oZ 099 0 720 Ischaemtclxan drxaseln.4061190 0 97 1 01 0393 TAaIJ rn-.4)a-uandardiaed risk ratio for arGad saraer of dtarh in taonwn by dcoAol-driwiltirq Aobtt of tAeAwtband C.Fusr of Husband'adnnking habrt death Non.dnnaee oocaa,ww Da. iy P m drtnker rare:drinker, Luna cancer (n - 174) 1 00 1 t 3 1 1!f 0. 396 Em")-sem/) aaMma fn .66)~ 1 i10Cancer nf ccrvra (n ..SO) 1-00. 092 139. 02920a4 0Mq. 09t4o$ie 095 0255 Stotnachnncertn 716)~ 1'00 I.ehaem&chortdneaae(n~406)1-00 109. 093. 0 567, 32 73 30 r___1 L ~ ~ 9or ette ~20 smowers Mon amo+<'tr Fomdrol pas6rve sm9h,nq (-) ts50 .0 ~ ' o aglo 70 ion smoker Totaii 1106906 N1. Fom-i.oi oasywe senokrng (r)'. () 21895 69 645 Populolron a9nroIrntM, 17366 (rdonsrnOker (Hon amoYer wives (Women wives 04 dhusbontltwtth with non smder amo4rnp hobt€) am0l~-q • husbonds )' hnb,t s) rio 1-Lung anccr ttstxtality, in women according to the presena or absence o( dircct and fattsiti.l indirect smokiag. Ducusido0 The possible effect of passive smoking was studied'by follow- ing many non-t:moking wives whose husbands had various smoking habits, and measuring their risk of developing lung cancer. Continued exposure to their btnb6mds' smoking irt- creased mortality fn3m lung cancer in non-smokers up to twofold, The extent of the increa€e in the risk of developing cancer reached' as high as 4•6 for non-smoking wives of agri- cultural workers aged 40-59 who smoked 20 or more cigatettes a day. The fact that there was a statistically significant relation (two-tailed p- 0-00097) i between the amount the husbands smoked and the mortality of their non-smoking wives from lung cancer suggests that these findings were not the result of chance. To' determinc w'hether such an effect was limited to lung urlccrs similar studies were conducted with other causes of dcath• Although therr seemed to be a relation between husbands' smoking habits and deaths from emphysema and asthma in their wives, the effect of passive smoking was srrongest with

, suttttsH MeDtCtl. JotrRra,u. vot.uME 282 17 JANUARY 1981 lung cancer. Passive smoking did not seem to increase the risk of developing stomach cancer, cervical cancer, or ischaemic heart disease. We found that smoking was the only habit of the husbands to affect wives' mortality. The absence of an effect of' husbands' drinking habits on mortality in their wives was shown as an example. ~ ~ ~ 20.0 t00 so 60 40 ?a 1-0 08 o-6 o+ 1947 56 Yecri 55 65 no 2-ABe-adiusted mortality for luna cancer in Japan (1947-78):. The most important confounding variables would have been urban factors. Similar observations were therefore made for agricultural families and for non-agricultural families, and a similar dose-response relation was observed in both groups. The effect of passive smoking was most striking in younger couples in agricuhural families, relative risk reaching 46, probably because of the lesser extent of the exposure to passive smoking outside the family in the case of rural residents. That the rate for non-smoking wives with husbands who were heavy smokers in urban families was lower than that in rural familics is puzzling but probably reflects a longer period of mutual contact of couples in rural families. Irt urban families some couples meet only for a short period in the day. Finally, the effects of passive smoking were compared with the effects direct smoking. The results clearly indicated that the effect of passive smoking is about one-half to one-third that of direct smoking in terms of mortality ratio or relative risk. In terms of attributable risk, however, the eHeet of passive smoking on lung cancer in women must be much, more important than that of direct smoking (fig 1), especially in countries such as atssMrutT.'I'be bot Ar:sm.rtis ealkd also Water-pepper, ae Cuinge. The ttsild' Arssmart is called dead' Arssrttan Petsiotria, or Peachwon, because the leaves art so'Iike the leaves of a peach-tree; it is also - - • called Plumbago. The mild has broad leaves set at the great red'joint of the stalks; with semicireular blackish marks on them,, usually either blueisb or whitish, with such like ssed following. The root is long, with many strings thereat, perishing yearly; this has no sharp taue (as another sort has, which is quick and biting) but rather sour like aotzel, or else a littlt drying, or without taste. It grows in watery places, ditches, and the like, which for the awst part, are dry in surnmer, lt Ao.vers in June, and the seed is ripe in August. As the virtue of both these is various, so ia also their government; for that which is hot and biting, is under the dominion of lvfars, but Saturn, challenges the other, as appears by that lead= coloured spot he bath placed' upon the leat. It is of a cooling and drying quality and vm effectual for putri5ed ulcers in man or bust, to kill worms, and cleanse the putrified pl.ees.. The juice thereof dropped in, or otherwise applied, oonsumes all oolds, swellings, uud dissolv.Kh the eongealed' blood of bruises by strokes, falls, .te. A piccc of the rooti or some of tlse seafs bruised, and 185, Japan where 730, of men but only 15°0 of women smoke. Therefore, although the relative risk of indirect smoking was smaller than that of direct smoking, the absolute excess deaths from lung cancer due to passive smoking must be important because of the large size of the exposed group. The age-adjustcd mortality rates for lung caacer have been sharply increasing both fer men and for women in Japan (fig 2). As qrtiy a fraction of Japanese women with lung cancer smoke cigvertes, the reasons why their mortality from _ lung cancer panllets that in men have been tmclear. The present study appears to explain at least a part of this long-standing riddle. This observatioo +lso questions the validity of the con- veatiorsaJ method of assessing the relative risk of developing lung cancer in smokers by comparing them with non-smokers. This study shows that non-smokers are not a homogenotu group and should be subdivided according to the extent of previous exposure to indirect or passive smoking. This work was supported' by Grants-in-Aid for Cancer Rcscarch from the Ministry of Health and Welfare. References r Brunnemann KD, Adams JD„Ho DPS, er .!: The ia>yucnce of tobacco smoke on indoor atmospheres.:1I. Volatile and' tobacco speeiLe nitro- aamines in main-aid sidestream smoke and theireontribution to indoor pol)ution: In: Proceed.ss of rAe trh' Jor.nConferrnu on tbe Senrrnt of Eevironanenta!' Pollu+.tnn. Keu Ork.+ru 1977. R'ashinaton: Amenean Chemical Society, 1978: 876-80i. s Brunnernann KD„Hoffrnann D. Cherninl!studies on tob.cco smoke LI9C. Analysis of volatik nitrosaro,nes in tobacco amoke and'polJittcd indoor environments. In: Waler EA, Griciure L, Casteanaro M, eds. Envrron- twnual asprcts of N-MUrosJ caepoundi. (IARC sciettti5c publintions No 19)Lyau: W H0, 1978:1i}56: a Whire RJ, Froeb FH: Sinall-sirways dysfunction in non-unokers eAroni- eally e:posedlo tobacco smoke. N'Ee17J Med 1980=:720-y. ' Hitayama T. Prospective studies on cancer epidemiology based on census poputation in Japan. 1in: Prxerdnrlt of XI Jntrrrutrarof Cancer Cow- sresi Florence. Cancer Epidermoloay andEnvrroarnentali Factors„ 3. Amsterdam: Ezccrpta Med u, 1975:26-35. s Hiny.rna T. Epidemiology uf lung cancer based on population studies. l~n :.Cli,ucal irr,ph:anon,s of ciff pollut ioe rexar.k. ChicaBo ::The Amerion Medical Associarion,1976:69-78:. `Hinyama T. Smoking and cancer. A prospective study on cancer epidemiology based oo census populaian in Japan. In: Procredint: of tAe Jrd trrorlJ Cart(rrewce aw S,isok~K ad Flealth 1'ly3: Washington: Department of Health Education and Wcltare, 1977:64-72. (DHEW Publiation No (N!'H) 77-741D. ) ' Hirayuna T. Prospecnve studies on cancer epidemiology based on census population in Japan. In: Nieburys HE, ed. TA,rd lwureaeiowa7 Symparrm at Drircriawand Preveetionn of Cancer. Pt1. Vol 1.. NewYork: Marcel, l)dcter,1977:1139-48. (Accepud 13 NoNewb'rr 1)d0)~ held to an aching tooth, takes aw.y the p.in. The leaves bruised and taid to the joint that bas a felon thereon, takes it away. The juice destroys worms in the ean,, being dropped into them; if the hot ersstttart be strewed in a chamber, it will soon kill all'the Eeas; and the herb or juice of the cold Arssmart, put to a horae or other cattle's sores, will drive away the fly in the hottest time of Stsmaser; a=ood handful of the hot biting Arssmart put under a horse'i aaddle, willl make him travel the better, although he were half tired before. The mild Ansrrsart is good ar.tirtst all impostbutnes and insammations at the beginning, and to heal sreen wounds. All i authors chop the virtues of both scxts of Arsuaart together, as men chop herbs for the pot, when both of them are of contrary qualities. The hot Arssmsrt grows not so high or tall as the mild doth, but has many leaves of the colour of peach leaves, very, seldom or a,rvtrr spotted; in other particulars it is like the former, but may easily be known fkom it, if yetrt will but be plcysed to break a leaf of it aoss your tongue, fur thc hot will make your tongue to smart, but the eold' will not. if you see them both together, you may easilyy distinguish them, bcmusc the mild bath far btoader leaves. (Nicholas Culpcpet (1616-54) TJw C"*eu Heroal, 1850.)