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( i;, _ ; 'r), aRITISH MEDICAL )OURNAL VOLUME 28217. IaNVAny 1981' 183 PAPERS AND SHORT REPORTS NOTICE This materisl may be pretect;A by ce~,.!gti?, /wr (fitk 27 iJ.S. C...), Non-smoking wives of heavy smokers have a higher risk of lung cancer: a study from Japan TAKESHI HIRAYAMIA Abstract In a study in 29 health centre districts irn japan 91 S40 non-smollting 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 smoktrrs: were found to have a higher risk of developing lung cancer- and a dose-response reLt3or'wss obses*ed. The relation between the husband's smoking and the wife's risk of developing lung cancer showed a similar pattern when analysed by age and occupation of the husband. The risk was particnl'arly 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 eaneer,, cervical eancer,, 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 effect was not statistically significant. The husband's drinking habit seemed to have so effect on any causes of death in their wives, including lung cancer. These results indicate the possible importance of passive or ibdirect smoking as one of the causal factors of lung cancer. They slso appear to explain the long- standing riddle of why many women develop lung cancer although they themselves are non-smokers. These results also cast doubt on the practice of assessing the relative risk of developing lung cancer in smokers by comparing them with non-smokers. Ilnttroduetion The possiblc consequences to the health of non-srnokers of llong-term exposure to cigarette smoke (passive smoking) should National Cancer Centre Researcb lastitute, Tokyo TAI:ESH~I H IRAYAMA, sui,.vri, ctiiof of eridcrnioioey division be studied thoroughly because the side-stream and second- hand smoke of cigarettes contain various toxic substances, including arcinogcns.s s The need for such a study incrased by the report of small-airways dysfunction in non-smokers chronically exposed to tobacco smoke.'' The effect of passive smoking on lttng cancer was studied by following 91 540 non-smoking housewives aged 40 and above and measuring their risk of developing lung cancer according to the smoking habits of their husbands. Methods To study the consequences to health of such factors as cigarette smoking, alcohol drinking. occupation, and marital' status, a pro. apective population stwlj• has bran in, progress in 29 hcalth centre districts in :i>< prefectures in Japan sincv the autumn of 1965. In total 265 118 adults (122 261 men and 142 057 womcn) aeed 40years and over, 91-99-;. of thcscnsus population, were intervicwcd and followed by establishing a recor& linkage system bctwtKn the nsk-factor rccords, a residence list obtained by spocial'ycarly census, and death eertiti:ates. , Since the ctfuet of direct smoking of cigarettes in this study has already bcon nported,! - my study fowsed on the effect of husband's smoking on the risk of lung cancer in their non-kmokiny w ivcs. Such obscrvation was possibl.• since dvtailcd qurstions about Itfcstyle, including smoking habits, were asked of husbanda and wives rnJ.~pen- dcntly at thue surt of this study. No subj.wtive bias was therefore conccivabl. ` v. A total of 346 deaths from lung cancer in women were rrcorded Q during 14 years of follow-up (1966-79); Of these women 245 were N marricd, and 174bftha.• were also non-smokers. These cases occurred W among 91 $40 non-smoking marncd womenwhosc husbands' smoking habits were studicd. Thc risk of lung emcer was earetully messured, ~ taking into considcration possiblc confoundina variabll•s. t~ Results u Wivcs of hs.vy smokers wsrt found to have a higher risk of develop- ~ ~ ing lung cancer than wives of non-smokers and a statistically significant dose-responsc rclationship, was observed (Mantcl-extension 7r test result being 3°99; two-uildd p- 000097). Ate-eccup.uon standard- ised annual mortality rates for lung cancer were 8'71100 000 (32 out of 21 895) when husbands wcrc non-smokers or occasional smokers,

184 (4 n(Fn, out of 44 1R4) w'hcn husf+and,, .vcre ex-smokers or dailc smnkcrsof I'-Io crgarcttcs, nnd'1',8 1(56 nut of15 146) when husbands were dail.' amokers of 20 on more cignratcs• Thrsc hgures gave risk ntios of I I>n, 1 61. and 2 08: respccai+'c11., A simil3r trend was ob- en-cd in agcand occupation;roups of husbands (tablc I): taaLS 1-Standa.lirsd .ortaliry far !istil cerucr im mlnrn by ee, elx>rp.eie~, w/ awrobrpr kabt7 of the larsbond ( jarwwt.krxu6 abw aaaeker). Husband'iannking!<abit: Nan-sarier Ea-amokcr er.1-19 ,day ;20idiy H+uMnt's pr: 40-d9 yrrn Prqulatirvnof~isrs' 14p2D 30676 20SM Nonfdeathsfrnmltaw6canen It 40 36 pccupau i nn-.un diard.iaed asortahtYn16061v SM 934 1)-14. Nralydi Kr: :`-i0y.an PoPularinn nf oives 7875 1311011 4177 honfdrathafre.mlunttsm 21 46 20 Occu ryunn-standa rdi red. mnnalle, ln0fU01379 2444. 2960 ftandardiacd nst ratio tee atlasrs 1'-00 111 aUa HsMnd~rrkiwt io.r.r~ nhrrr Popuhtn•rtnfricrs 10i4(f6 20n14 9391 Nonf dcath. fr..mlunRUncer, 17. 32 24. Aac-standsrdncd mnrtahry 1100 000 9-5~/ 1702 1840 Hrala+d caarkint rlsrmArrr Populacmn of .rre• Nonl~deathsfromlunaesnccr 11 469: 15 24 140 34 16 070 32 Aae-standardt•cd ' monahty 100 000 913 3 1046 11778 SnndardisedTtskrnrofwalloccuparans 100 . 143 190 The relation between tho husband's smoking habit and the wifc's risk of developing lung cancer was panicularl.• significant in agri- cultural families when the husband was aged 40-59 at enrolment (Mantcl+cxtcnsion chi' being 259'a or two-tailcd p=00094); lung cancer risk ratios were 1.00; 3 17. and 4 5T .chen husbands were non-amokcrs or occasional'smokcrs„ea-smokcrs or smokers of 1-19 ei(tarottcs daih', and smoken of 20 or more eigarcttcs daily respcctiveh- (Itahk 11):, TAalt Il-,tfona/rrx• fnr funP taRcrr, in warncn by occupatitwr awdby sreokirtt Aabt ofburband'awo•rqr twrs afrd 10-59 (Panenr knutf a wnw-nrwkn) Husband'a smnkina habit: ARrrcuGural.orkcn: PrTulannn of -cs 9 999 No of deaths from luna uutcer . 3 Mnnality 100 000 }-4aOthe...rtken Non4moker Es-atnokn ::+a0idaYor t-r9rd.y 12 753 7130 20 16 11-03 17-92 PnOulMinnafuirea a 02l 1792} 13431. No.of ddatM fn•m lungt~ces Mortdity100000 a 715 tiO9 114R iirandirdiaed risk rniu for dl eocvRadr 1-00 1.67 236 Thv husbanda' smoking habits seemed to have no cffcet on thcir wivcs' risk of d'ctvlo)ning other tnaior eancen, such as canccn of the stomach (tl=7t6) and of the cervix (n><25f)) or ischacmic heart discasc (n=4O6). The risk of dovcMping cmphvscma nd asthma seemed to be hiRher among the non-smoking wives of smokcrs, but the affrct was not stntisricalli.significant (tablr l l IN. Othcr characteristics of thofiusbands, such as their alcohol drinking hahirs didnot aftcct mortality from lungcanc.cr in thcir svii'cs. Thce rolawr risk ratios of death from lung cancer svcrr 1-(10. 1 13, and 118 (p=1139f,respcctis•cl'•v v'h:n hushands were nnn-dhnkcrs, occasional or rare drinkers, and daily drink;n. SimiHrr results wcrc found with other nusesof death (nhlclV): Finallv; thceRcct of passive smoking w•aa eomparcd'with the effect of direct smoking. The cftuct of paasicc smoking was around onc-half to one-third that of direct smoking. The relaritr risk of developing lung cancer by passive smoking was about IrR compared with about 3-8 in direct smokers (fig 1); enms)f htFDICAL )otrevAL voLU..t>:'• 2P2 17 JA.';VAav 1981 TA1l1F 111-Arr-ncrnpana+ atandardrtedruk,r.rnn f:+- trlttrrdc,nur+ofdrarh rn toowerr by tnro6n,r hab1+ nJrkr kr~band( ~o+rrnr,br.~r/f, a non.i n~nkr.) Causc nf death Hu,band's .m-i.inR habil Nnn-smoke r Ea--kn: or 1'-~19 dap. ~'20daY~, p^'alue Luna canccr /n - 174: . 1 00 1 61 2oe 0.001 karpMxma.a,thma,n~66' 1-Q0 179 1i49. 0.474, Gncet ollcc-nin-2i0;1100 1, I3 1114 0249. Stnmachnnccrln-716~ lrel0 1>02 099 0720 lsch.em,cbtandnease:(n~4n6! 1YI0. 097 1A3. 039'3 TNlIJ r9-Atr-arandordiicdritk'rario.for.ukcrrdrtrsctof deark in tonmrn by0lydrol-drirtkittg habtt of tke kMrba•nd Fiuse of Husband's drinkin habrt th d es Non-dntsker Ocu»onal Daily R or dnnkcn rare dnnkv Lunacancer(n- 1741 . 100 113 1, 1' . a3o6Emph,sema, a•rbma:(n ~ 66). 1 ito 0.92 1. 39 0 292 Gancer,nf ccrrn tn • an) 100 0 a4 OA9 0114 Stomachcanccrtn71611-00. 0P6 095 0285 l.chaemic heart dncase in - 406) 100 1-09 093 0567 32 79'. a : r 9orrtte , --. ,g20 anlfkfrS Non sm06ar: Ramd,ot paf6rv4 s+mak'rnq (r1 EC . tSYJ .o pg10 r totol 1 e'o1 Man smMer 106 906 O N Fprn,1,01 Oas}+vt 6rrloMlrlq (1.). 0 . 21,695 69 645 17766 Populotion ot 9nro/ nxnt, (Non art,pher (r/on snqktr wirfs ( Wovnen wrvK of d'husban0iwrth wrth nonsmortr smokrnqha0rts) srna,.nq • htrsbands ) hob-t s) na 1--Lung cancer mortality in women 6eoording to the preaencs or6bsenee of diren and f6miliai indirect smoking. DLCuaif.04 The possible effect of passive smoking was studied by follow- ing many non-smoking wives whose husbands had various smoking habits, and measuring their risk of developing lung cancer. Continued exposure to their husbands' smoking in- ~ aeased mortality from lung cancer in non-smokers up to © twofold. The extent of the increase in the risk oL developing cancer reached as high as 4'6 for non-smoking wives of agri- ~ eultural workers aged 40-59 who smoked 20 or more cigarettes W a day. The fact that there was a statistically significant relation ~ (nt-o-tailbd p--0-0009r) bctwecn the amount the husbands smoked and the mortality of their non-smoking wives from N lung cancer suggests that these findings were not the resultofCA chance. To determine whether such an effect w-as limited'to lung eancer, similar studies were eonductcd with other causes of~ dcath, Although there seemed t'o be a relation between husbands' smoking habits and deaths from emph}-srma and asthma in their wives, the effect of passive smoking was strongest with

, I , tiRlTdSH~MEDtLAL JOURNAL VOLUMI: 2gZ17]AbrUARY19fS1i 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 afirct wives' mortality. The absence of an effcct of husbands"drinking habits on mortality in their wives was shown as an example. 165 Japan where 73°0 of men but on)y 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 cancer have been sharply increasing bonh frr men and for women in Japan (fig 2). As qnly a fraction of Japanese women with lung cancer smoke eigarettes, the reasons why, their mortality from lung cancer parallels that in men have been unclear. The present study appears to explain ar least  part of this long-standing riddle. This observation *iso questions the validity of the eon- ventional method' of assessing the relative risk of developing lung cancer in smokers by comparing them with mon-smokers. This study shows thatnon-smokers are not a homogenous group and should be subdivided according to the extent of previous exposure to indirect or passive smoking. This work was supported by Graatt-in-Aid for Cancer Research fromrhe Ministry of Hcalthand Welfare. o-4 1947 50, Ysorts 55 60 65 7E1 75 78 rtG 2-Age-adiusted mortality for lung cancer in ]apan (19a7-78):. The most important confounding variables would have been urban f.ctors. Similar observations were therefore made for agricultural families and' for nan-agriculturaJ families, atld a similar dose-response rrlbtion .+oas observed in both poups. The effect of passive smoking was txast striking in younger couples in agricuhural: families, relative risk reaching 4•6e 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 w•ho were heavy smokers in urban families was low er than that in rural familics is puzzling but probably reflects a longer period of mutual contact of couplcs in rural families. In urban families some couples meet only for a short period in tbe day. Finally, the effects of passive smoking were compared wiih 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 re]ative risk. In terms of attributable risk, however„the effect of passive smoking on lung cancer in women must be much more important than that of direct smoking (fig 1), especially in eountries such as AttssatAttT. The hot Arsstnart is called also W.ter-pepper, or Culnte. The mild Arssmart is called dead Arssmart Persioru, or Peacbwort, because the leaves are ao like the leaves of a peach-tree;,it is also ' - • called Plumbago. The mild Isas brwd leaves set at the great red joint of the stalks; with semicircular bLekish marks on them, usually either blueisb or whitish, with such like seed foUowing.,The root is lorte„with tstany strinBs thereat, perishing yearly; this bas no sharp taste (as another sort has, which is quick and biting) but rather sour like sorrel, or else a little drying, or without taste. It grows in watery places, ditches, and the like, which for the mom part are dry in suatmer. It flowers in June, and the seed is ripe in August. As the virtue of both thcsc is various, so is also their government; for that which is hot: and biting, is under the dominion of Mars, but Saturn, challenges the other, as appears by that lnd-n cobetred apot he bath placed upon the leaf. Lt is of a cooling and drying quality and very effectual for putrified uken in man or beast, to kill worms, and cleanse the putrified places. The juice thereof dropped in, or otherwise applied, oonsurttts all colds, swellings, and dissolvrth the corsgnled blood of bruisn by strokes„folli, etc. A pivcc of ihe root, or some of the secds bruised, and R'eferetsces r Bruanemann KD, Adams JD, Ho DPS, er eL The inDueoa of tobacco smoke on indoor atmospheres. II',. Volatile and tobacco specific nitro- samincs in main-aid sidrstrcam srtwk'e and'their contribution to indoor pollution. In: Pnxeed,nrr of rAr Ph Joinr Confsrrwce on tAe Stnnnr rf Eiwvonn,enrol Pollum,nt. New Wrlsaru1977. aCashington:.Amencam. Chemical Society, 1978: 876-80. ' Brunnemann KD, HotTmann D: Chnnical'studieson tobacco smoke LIX. Analysis of volatile niTrosamtnes in tobacco smoke and polluted indoor environments. In:, Waler EA, Griciutc L, Caucgnaro M, eds. Ewt•,ron• rweual atpectt of N-nrcra,i toinpownda. (IARC seientific publications No 1'9)iLyonrc WHO, 197B:1N3-56: a C+hite R],,Froeb FH. S,nallbairways dysfunetion in non-smoken ehroni- ally exposed to tobacco smoke. N EntfJ hfed 198o;=:720-3. e Hirsyama T:,Prospectivc studies on uncrr epidemiology based oroeensus population in Japan. 1'n: Procrrd nrr of Xf /nrr+nar,ona! Caun Con- sresu. Florence. Cancer Eprdemtolo`y and Envnonmental Factors, 3, Amsterdam: Eseerpta Medics, 1973:26-35. a Hirayama T. Epidemiology uf lung cancer based on population srudict. In: Clini:.al implicstronr of air pollruan reuar,h: Chicago: The American Medical Association,1976:69-78. ' Hirayama T: Smoking and nncn. A prospective study on cancer epidemiology based on census popuLtioo in.Japan,,In: P+ocetdrrwt.of sAe Jrd WorIJ Caqferente aw SraoArrtr and Health 1975. Washinaton; Department of Hcalth Education and Wellsre, 1977:65-72. (DHEW Publication No (NIH) 77-141J. ) ' Huayuoa T. Protpecti.e studres oa cancer epidemiology based o0 census population:in Japan. ln: Nieburp, HE, ed. TAird liurrnar,oe.al' Sywpo„r,w on Deteetion and P+everuion of Cancer. Pt 1. Vol 1. New York; Marcel, t)ekser, 1977:11J9-4B. (Aasptad 13 Nweabrr Jl80) held to an aching tooth, takes away the p.in. The laves bruised and laid to the joint that bas a felon thereon, takes it awsy. The juice destroys wrorms in the ears, being dropped into them; if the hot. Anstnart be strewed in a chamber, it will soon kiU all the ffeas; and' the herb or juice of the cold Arsstmrt, put to a horse or other: ottie's sores, will drive away the fly in the hottest titae of Summer; a good handful~of thc hot biting Arssman pun under a horse's saddle, will make him travel the better, although he were half tired before. The mild Arssmart is good a`.unst all imposthumes and iit8arrunrtions at the begirutirt=, and to hcal grn-cn wounds. All authors chop the virtues of both sorts of Arsstnart together, as men chop herbs for the pot, when both of them are of contrary qualities. The hot Arssraart srows not so high or tall as the mild doth, but has a,zny, leaves of the eoloLLr of: peach teaves, very seldom or nLver apottcd'; in other particulars it is tike the former, but may easily be known from it, if' yon will but be pleased to bruk a leaf oflt cross your tongue, fur thc hot will make your tongue to smant,,but the cold will not. lf you see them both together, you may easily distinguish them, because the mild hrtll far broader leaves: (Nicholas Culpeper (1616-54) Tke Complete Herbd, 1B50.)