Cad. Saúde Púb lic a, Rio d e Jane iro , 14(Sup. 3):41-66, 1998
N o n - H o d g k i n ’s lymphoma risk derived
f rom exposure t o organic solvents:
a review of epidemiologic studies
Risco de linfo ma não -Ho dg kin re sultante
da e xpo sição a so lve nte s o rg ânic o s:
re visão de e studo s e pid e mio ló g ico s
1 Ce n t ro de Estu do s d a Sa ú d e d o Tra bal h a do r – CESAT. Ru a Pe d ro Lessa 12 3, Ca n e l a , S a l va d o r, Ba h i a
4 0 1 1 0 - 0 5 0 , Bra s i l . 2 In stitu t o de Saú de C o l e t i va , Un i ve r s i d a d e Fe d e ral d a Ba h i a . Ru a Pa d re Feijó 2 9, Ca n e l a , S a l va d o r, Ba h i a
4 0 1 1 1 - 1 7 0 , Bra s i l . m re g o @ l o g n e t . c o m . b r
M a rco An t ô n io V. Rêgo 1 , 2
Abst ract Th e ra t e of n on -Ho d g k i n’s lym p h om a s (N HL) h a s in crea sed a rou n d t h e w o rld d u rin g t h e la st d eca d es. Ap a rt fro m t h e role o f t h e h u m a n i m m u n o d ef ici en cy v iru s (H IV ) in f ect io n in t h e d ev elop m en t o f N H L, ex p o s u re t o ch e m i ca l a gen t s li k e p h en o x ya cet i c p est icid es, h a i r d yes, m et a l fu m es a n d orga n ic solv en t s a re su sp ect ed t o b e in v o l ve d . Th e p resen t re v i ew ev a lu a t es t h e resu lt s of st u d ies t h a t d irect ly or in d irect ly sea rch ed for a n a ssocia t ion b et w een solv en t ex p o s u re a n d N HL. Th e select ed st u dies com p rised t h ose p u blish ed fro m 1979 t o 1997, d esign ed t o in ve s t i-ga t e risk fa ct ors for N HL, w h eth er sp ecifica lly lo ok in g for so lv en t ex p o s u re or for gen era l risk s in w h ich solven t ex p o s u re cou ld be in clu ded . In 25 of th e 45 re v i ew ed stu d ies (55.5%), fift yfou r st a t i st ica lly sign ifi ca n t a ssoci a t ion s bet w een N HL a n d so lv en t ex p o s u re rela t ed o ccu p at ion s or i n -d u st ries w ere re p o rt e -d . St a t ist ica l sign ifica n ce w a s m o re f requ en t ly sh ow n i n st u -d i es w h ere sol-v en t ex p o s u re w a s m o re a ccu ra t ely d ef i n ed . In ei gh t een of su ch st u d ie s, 13 (72.2%) d ef in ed o r su ggest ed orga n ic solven ts a s p ossible risk fa ct ors for N HL.
Key words N o n - Ho d g k i n’s Ly m p h o m a ; Occu p a t ion a l Ex p o s u re ; S o l ve n t s ; Ep i d e m i o l o gy
Resumo A t a x a d e in cid ên cia d e lin fom a s n ão-Ho dgk in (LN H) t em au m en t a d o m u n d ia lm en t e d u ra n t e a s ú lt im a s déca d as. Além d o p ap el d a in fecçã o p elo v íru s da im u n o deficiên cia h u m a n a ( H I V) , su sp ei t a se q u e a ex p o si çã o a a gen t es q u í m ico s, com o o s p e st i ci d a s f en ox i a c é t i c o s , t i n -t u ras de ca belo, fu m os m e-tá lico s e solv en -t es orgâ n icos, es-t eja en vo l v i d a . A p resen -t e rev isão a va l i a os resu lt a d o s d e est u d os q u e d iret a ou in d iret a m en t e p ro c u ra ra m p or u m a a ssocia çã o en t re ex -p o si çã o a solven t es orgân icos e LN H. Os est u dos selecion a d os co m -p reen dem aqu eles -p u blica d os e n t re 1979 e 1997, q u e in v est i ga m fa t ores d e risco p a ra LN H, sejam os qu e esp ecif ica m en t e a n a-li sa m solv en t es orgâ n i cos, seja m o s qu e a n a a-li sa m ri scos em gera l , e n t re os qu a i s a ex p o si çã o a s o l v en t es p u d essse esta r in clu ída . Em 25 do s 45 est u d os rev isa dos (55,5%), f o ra m cit ad as 54 a sso-ci a çõ es est a t i st i ca m en t e sign if ica t iv a s en t re LN H e o cu p a ções rela sso-cio n a d a s à ex p osi çã o a so l-v e n t e s . A p resen ça de sign if icâ n cia est a t í st ica fo i el-v i d en cia d a m a is freqü en t em en t e em est u d o s n os q u a is a ex p o si çã o a solv en t es f oi d efi n id a d e f orm a m ai s a cu ra d a . Em 18 d est es e st u dos, 1 3 (72,2%) defin iram o u su geriram ser os solv en tes orgân icos p ossív eis fa t ores d e risco p a ra o s LN H.
Cad . Saúde Púb lic a, Rio de Jane iro , 14(Sup. 3):41-66, 1998 I n t ro d u c t i o n
Th e in c rea sin g ra te of n o n Hod gkin lym -p h om as (NHL) a rou n d th e wo rld d u r in g th e la st d ecad es h as b een exh a ustively d em on -s t r at ed (Lin o -s e t al., 1986; Zh e n g et al., 1992;
D e vesa & Fe a r s, 1992; Ho l f o rd et al., 1992;
Ha rtge & De vesa , 1992; Costan tin i et al., 1992; Rab kin et al., 1993; Ha rtge et al., 1994; Pa l a c k d-h a r ry, 1994; Scd-h err & Mu e l l e r, 1996; Se ow et al., 1996; Vi n e i s, 1996). On th e on e han d , som e s e a rch sh ows th at th e in cre ase is m a in ly a resu lt of viral in fection , p ri m a rily th e h um an im -m u n od eficien cy viru s (HIV) in fection (Ha rn l y et al., 1988). On the oth er han d , it has been d
is-c u ssed th at th is viru s h a d little im p ais-c t o n t h e NHL in ciden ce tren d s (Ha rtge & De vesa, 1992), an d th at th e in crease in NHL was ap p aren t b e-f o re th e arr i val oe-f th e ac q u ired im m u n o d ee-fi- efi-c ien efi-cy syn d r om e (AIDS) (Ho l f o rd e t a l., 1992; Carli et al., 1994). T h e re f o re, this su ggests other u n k n own en viro n m en tal cau se s, in clu d in g ch em ical exp osures (Lon go, 1994). Oth er stu d-ies h a ve p re se n ted t he ro le of ch an ges in th e c ri t e ria d isea se classific ation an d of im p r ove-m en t in diagn osis techn ology to exp lain p ar t of the rate growth (De vesa & Fe a r s, 1992), m ain ly for the m arked in crease in extra -n od al NHL in o ld er p eop le (Cozen & Be r n ste in , 1994). T h i s exp lan ation does n ot agree with the fin d in gs of Lu tz & Colem an (1994) for p ri m a r y c ere b ra l lym p h om a. Th is d ia gn ostic b ia s h as b een d e-n ied (Ba e-n k s, 1992) ae-n d a rea l a e-n e-n u al ie-n cre a s e in N HL r at es o f 4% in re ce n t ye ar s in Bri t a i n ( Ca rt w righ t, 1992) an d a re ce n t in cr ea se in De n m a rk (Hjalgr im et a l., 1996) h ave b een d e m o n s t rated . Am on g the ch em ical exp osu re s, t h e re are seve ral agen ts susp ected of bein g in -vo l ved in the d evelop m en t of NHL (Blair et al.,
1992; Pe a rce & Be t h w a i t e, 1992; Vi n e i s, 1996). So m e exam p les are th e p h en oxya cetic p est i-c i d e s, h air d ye s, m etal fu m es an d organ ii-c sove n t s. Th e goal of the p resen t review is to eva l-uate th e resu lts of th ese stud ies wh ich d ire c t l y or in d irectly looked for an association betwe e n o rgan ic solven t exp osu res an d NH L.
M e t h o d s
Th e select ed stu d ies in c lu d ed th o se d esign ed to in vestigate risk factors for NHL, wh ether th e m ain ob jective was sp ecifically to look for sol-ven t an d NHL re lat io n sh ip or to fin d ge n era l r i s k s, fro m wh ich solven t exp osu re c ou ld a p -p ear (Tab le 1). In t he latte r on e s, e x-p osu re t o o rgan ic solven ts was deri ved from the in form a-tion of th e occu p aa-tion or the in d ustry in which
th e st u d y su b je ct s we re en r olle d . T h e re f o re, st u d ies wh ose m a in ob jectives we re to stud y g e n e ral m or t alit y p at tern s, c o n d u c ted wit h in p a rtic ular wo rk e r s’ co h o rt s, like m ec h an ics, p a i n t e r s, p r i n t e r s, d ry clean ers, re f i n e ry, p etro-ch em ica l, c h em ica l an d r u b b e r wo r ke r s we re n ot selec ted , even th ough som e of th em cou ld h a ve in vestigated th e relation ship of in terest in th is re v i e w. In th e sam e way, the stud ies lin kin g all oc cu p at io n s an d all c au ses o f d isea se o r d ea th , th ose foc usin g on NH L an d t h e ro le of oth er sp e cific exp o su re s su c h as p e st icid es, sm okin g, su n ligh t, et c., a n d th ose in vo l v i n g c h i l d ren a lso we re n ot re v i e wed . St u d ies th at h a d a fu r t her re - a n a l y s i s, an d released a n ew p ub lication we re evaluated again . It is also im -p o rtan t to n ote that m ost selected studies we re w ritten in En glish lan gu age a n d we re p u b -lish ed from 1979 to Ja n u a ry/ 1997. The m eth od of selectio n was b a sed o n th e lin kage o f t h e w o rd s lym p h o m a a n d oc cu p a tio n a l, en viro n -m e n tal o r solven t exp o su re u sin g M EDLINE d at a fr om 1966 to 1997. Th e sea rc h was co m -p lem en ted by lookin g for other stud ies cited by the au th ors of th e p reviou sly selec ted in ve s t i-g a t i o n s.
R e s u l t s
An ob ser va tion b ased on a c lin ical ca se seri e s was d on e in a co m m u n ity c om p osed o f 117 Cau c asian in d ivid u als, from 1968 to 1974 (Ca -p u r ro, 1979). In t h at are a, wh ere a ch em ica l p lan t was lo cated , so lven t exp osu re was m ea-s u red in th e en viron m en t an d d etected in 20% of th e visit s. Also, so m e solven t s like m e th yl isob u tyl ke to n e, b e n ze n e, ch loro f o r m an d t ri c h l o roeth ylen e we re detected in the b lood of th e re s i d e n t s. Twe n ty t hre e c ases o f ca n ce r we re listed , eight o f t h em we re lym p h o m a. Co n s i d e rin g sp ec ific ally the th ree d ea th s d u e to lym p h o sarco m a in th is six year p e riod , the relation between ob served an d exp ected cases was 3/ 0.0187 = 160 fold .
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LS, RR = 2.1. Am o n g su b jects 45 years old an d ove r, with in t he seve n oc cu p at ion s for wh ich age distribution s we re ava i l a b l e, th e n u m ber of d eath s ob served was sign ifican tly h igher th an th e n u m b er of d ea th s exp ec te d for th e two typ es of lym p h o m a: RCS, ob se r ve d / e x p e c t e d (O/ E) = 1.7 (p <0.01) an d LS, O/ E = 2.1 (p<0.01). Th e se fin d in gs we re d iscu ssed an d c ri t i c i ze d for t h e wa y Vian n a & Polan (1979) h ad go tt en th e in form ation ab ou t oc cup ation s from b oth d eath ce rtifica tes an d th e U.S. d ecen n ial cen -s u -s. It ws -said that th e-se -source-s are in com p a-ra b le with eac h oth er an d th at the y sh ou ld h a ve calcu lated p ro p o rtion ate m ortality ra t i o s, b ase d on ly o n occu p a tion a s d efin ed o n th e death c e rtificates (En t e r l i n e, 1979).
Th e age-ad ju sted m ortality rates of NHL in 3,056 c ou n tie s o f t h e Un ited St ate s b etwe e n 1950 an d 1975 we re ve rified utilizin g an ecolog-ic a l d esign (Can t or & Fra u m en i Jr., 1980). It s h owe d su gge stive a ssoc iat io n s in a m u ltip le re g ression an alysis between NH L rates am on g wh ite m ales an d five in d ustrial gro u p s, in clud -in g p r -in t-in g an d p u b lish -in g (sign ifica n t at p < 0.025), p etr o ch em icals a n d r u b b e r p ro d u c t s. Th ey d id n ot fin d a n association for o th er p o-ten tial solve n t - related in du stries su ch as fu rn i-t u re, m achin er y an d eleci-tri c a l .
The first stud y wh ich d irectly looked for th e relation sh ip b etween lym p hom a an d exp osu re to solven ts (am on g oth er exp o sures) was p er-f o rm ed in Swe d en (Ha rd ell et a l., 1981). T h e y st u d ied all 169 m en a d m itt ed t o t h e De p a rt -m en t of On cology in U-m ea with 109 d iagn osed NHL an d 60 Ho d g k i n’s disease (HD), an d eigh t c o n t rols m atched by age, sex an d resid en ce for each livin g case an d 10 for each deceased case m a tc h ed a lso by ye ar o f d eat h , fro m t h e Na-tion al Pop u la Na-tion Re g i s t ry. An alysis o f h igh g ra d e a n d low gra d e exp osu re p r od u c ed a n od d s ratio (OR) = 2.8 (1.6- 4.8) an d a n OR = 1.2 (0.5-2.6), re s p e c t i ve l y. Ex p o s u re to styre n e, t ri c h l o ro e t h y l e n e, perc h l o roethylen e an d b en zen e am on g the h igh gra d e exp osed in d ivid u -als gave greater risk th an exp osu re to oth er or-gan ic solve n t s, OR = 4.6 (1.9-11.4). A m odifyin g e ffect was fou n d wh en com b in ed exp o su re to o rgan ic solven ts an d p h en oxy acids, OR = 11.2 (3.2- 39.7) an d c hlor op h en ols (eigh t exp o se d an d n o exp osed con trols) we re an alyze d .
Th ese d ata we re re a n a l y zed (Ha rd e l l et al., 1994) an d th e au th ors fou n d th e followin g re-su lts: carp en te r: 13 exp osed cases/ 36 exp osed c o n t ro l s, OR = 1.1 (0.6-2.4); m ech an ic: 5/ 7, OR = 2.5 (0.7-9.6); m otor m echan ic: 7/ 20, OR = 1.3 (0.5-3.4); all orga n ic solven ts: 45/ 88, OR = 2.4 (1.4-3.9); h igh grade exp osure: 31/ 50, OR = 2.9 (1.6-5.6); low gra d e: 14/ 38, OR = 1.8 (0.8-3.8);
b en zin e: 3/ 1, OR = 2.8 (1.8-730); th in n er: 11/ 14, OR = 3.4 (1.4- 10); tri c h l o roeth ylen e: 4/ 4, OR = 7.2 (1.3-42); tu rp en tin e: 5/ 7, OR = 3.3 (0.9-17); white sp irit: 12/ 20, OR = 3.2 (1.3-8.3); degre a s-e r: 7/ 4, OR = 11 (2.9-72); m u ltiva riats-e an alysis – h igh gra d e OR = 3.5 (1.7-7.1); low gra d e, OR = 1.1 (0.5-2.7); organ ic solven ts (for lym p h ocytic an d well differen tiated NHL), OR = 2.9 (1.3-6.6). Th e m ortality p atte rn s of workers we re de-fin ed in t wo st yren e- b u t ad ien e ru b b er (SBR) p la n t s with sp ecific foc u s on h em a to p oie tic an d lym p h atic m align an cies (Me i n h a rd t et al., 1982). It was a re t ro s p e c t i ve c o ho r t m or t a l i t y stu dy th at re c e i ved in form ation from 1,662 in -d ivi-du als (34,187 p / y) in p lan t A, 1,094 in -d ivi-d- ivid-u als in p lan t B (19,742 p / y) th at gath ered in for-m ation ab ou t b u tadien e, styren e an d ben ze n e l e vels in th e work p l a c e s. On ly wh ite m ales with a t le ast six m o n th s o f n o n -m a n agem en t a n d n o n a d m i n i s t ra t i ve em p loym en t we re in c lu d -ed in their an alysis. They foun d stan dard m or-tality ratio (SMR) = 155 (p lan t A) an d 78 (p lan t B) for lym p h atic an d h em atop oietic tissue s in g e n e ra l (In t e r n a tion al Cla ssification o f Di s-eases – ICD 220-205) an d SMR = 181 (p la n t A) an d 132 (p la n t B) for lym p h o a n d re t i c u l o s a r-c om a (ICD 200). Th ese e xr-c esse s in m ort a l i t y we re n o t st at istically sign ifican t. Th e a u th o rs con clu d ed th at their fin d in gs con tin ue to sug-gest th a t th e p ro d u ction o r m an u fa c tu r in g o f SBR m ay b e a ssoc ia ted with an e xc ess of lym -p h atic an d hem ato-p oietic n eo-p lasm s.
A h osp ita lb a sed c a se co n tr ol st u d y c on -d u cte-d in Italy -d i-d n ot fin -d p ositive resu lts for i n d u s t ries (Fran co & Po n t e, 1983). In the chem -ical an d p h ar m a ce u t ic al in d u str y th ere we re fou r exp o se d c a ses (EC), OR = 0.16; t ext iles, sh oes an d leath er, 21 EC, OR = 0.50; p ap er an d p r in t in g, th ree EC, OR = 0.90 an d ru b b er an d p l a s t i c s, th ree EC, OR = 0.33. An im p ortan t as-soc ia tion wa s seen for wood w ork e r s, with 14 EC an d OR = 5.55 (2.39-12.85). Th e au thors dis-cu ssed the role of som e agen ts used d urin g the m a n u f a c t u re an d treatm en t of wood, like ben -ze n e, c h lo ro p h e n o l s, p h en oxyac id s a n d c o al t ar d eri va t i ve s. In t h is stu d y, c ases we re 282 NHL an d 387 HD (347 m ale an d 322 fem ale p a-t ien a-t s of b oa-th sexes a d m ia-ta-t ed a-to a-th e Clin ica Med ica A. Fe r rat a – Un i versity o f Pavia , fro m 1969 to 1980, d ia gn o se d as m align a n t lym -p h om a. Co n t rols we re 757 m ale an d 588 fem ale p atien ts ad m itted to an in tern al m edicin e u n it in Pavia from 1975 t o 1980. Occu p a tion s we re d efin ed as p rop osed by th e An n u ario St a t i s t i c o It a l i a n o. The an alysis d id n ot con sid er th e NHL
an d th e HD sep ara t e l y.
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con du cted with m align an t lym p h om as in m ale road tra n s p o rt workers aged 15 an d ove r, d iag-n ose d fr om 1973 t o 1977. Co iag-n t r ol iiag-n d ivid ua ls we r e ran d o m ly ch osen from o th er c an c er p a-t i e n a-t s, m aa-t ch ed 1:1 b y age, sex an d regio n o f re s i d e n c e . Am on g a ll lym p ho m a s (426), 256 we re re c o g n i ze d as N HL (ICD 200 an d 202). Th e resu lts d id n ot rea ch sta tist ic al sign ifi-c a n ifi-c e, an d th e a uth ors im p lied som e p ositive fin d in gs to possible exp osure to exhau st fu m es. T h u s, th e followin g results we re re p o rted : ICD 200: d r i vers o f b u se s an d co ac h es, OR = 1.16 (0.60- 2.26); dri vers of oth er road p assen ger ve-h i c l e s, OR = 0.95 (0.48- 1.88); d ri ve rs o f ro a d good s ve h i c l e s, OR = 0.93 (0.711.22); bu s con -d u c t o r s, OR = 0.57 (0.12-2.25); lorr y -d r i ve r s’ m a t e s, etc.: n o cases; ICD 202: d ri vers of bu ses a n d co a ch es, OR = 1.63 (0.62-4.52); d r i vers o f other road p assen ger ve h i c l e s, OR = 1.67 (0.68-4.32); d ri vers of road good s ve h i c l e s, OR = 0.90 (0.63- 1.28); b u s c on d u c tors, OR = 2.67 (0.64-15.6); lorry drivers’ m ates, etc.: n o cases ( Ba l a ra-jan , 1983; Ba l a rara-jan & Mc D owall, 1983).
All n ew cases of lym p hoid m align an cies d iagn ose d b e twee n Oct ob er / 1979 an d De c e m -b er/ 1981 we re selected am on g ad u lt re s i d e n t s in six h ea lth d istr icts in Yo rk s h i re Hea lth Re-gion . T h e re we re 81 m ale an d 77 fem ale NHL, 48 H D, 66 c h ro n ic lym p h o cyt ic le u kem ia a n d 13 acu te lym p h ob la stic leu kem ia cases. It wa s a h osp ital-b ased case-con trol stu dy wh ere th e c o n t rol grou p was p erf o r m e d by n on -c an c er h osp ital p atie n ts (162 m ale an d 154 fem ale for NHL ca se s), m a tch e d fo r age, sex a n d ge o-g rap h ic area in a ratio of 1:1. Past occu p ation s an d selec ted exp osu res we re an alyzed an d the f o l l owin g resu lts we re ob served: oc cu p ation al e x p o s u re to solven ts (exclud in g b en ze n e ) , OR = 1.52 (0.70-3.26) m a le a n d OR = 7.71 (1.24-47.93) fem ale; p etroleum in d ustri e s, OR = 4.21 (0.54-32.79) m a le; solven t u se as h o b by, OR = 1.39 (0.30-6.46) m ale; b en ze n e, OR = 0.49 (0.21-2.0) m a le; p e trol p ro d u c t s, OR = 0.59 (0.25-1.39) b oth sexes; h a ir sp ra y s, OR = 1.49 (0.75-2.95) fem ale; hair sp ra y s, OR = 4.67 (1.50-13.63) fem ale >65 years o ld . The n u m b e r of exp osed c a ses was n ot re f e r red , n eve rt h ele ss it c an b e i n f e r red th at they we re sm all by lookin g at the l a r ge c o n fid e n c e in t er va l s, in clu d in g th o se s t a tisticaly sign ific an t assoc iat ion s we re seen am on g wom en (Be rn a rd et al., 1984).
A n e w p a p e r with th e co m p let e Yo rk s h i re stu d y d a ta set w as p u b lish ed in c lu d in g case s d iagn o sed u n til De ce m b er / 84 (Ca rt w righ t et a l., 1988). Th e fin al rate b etween con trols an d
cases was 1.7. At that tim e, 437 cases (244 m a l e s a n d 193 fem a les) a n d 724 c on trols we re stu d -ied. NHL cases we re con firm ed by the Re g i o n a l
Hist op at h o logy Lym p h o m a Pan e l. Th e n ew an alysis sh owed th e followin g results: solve n t s, OR = 1.2 (0.9-1.5); glu es, OR = 1.8 (1.2-2.6); an d oth er n on - sign ific an t asso cia tio n s in solve n t rela ted o cc u p ation s, h owe ver w ith n o m e n -tio n ed OR value : c h e m ica l wo rk e r s, p r i n t e r s, p ain ters an d de cora t o r s.
A p op u la tion -b ase d ca se-c on tro l stu d y wit h all in c id en t case s of m ye l o p ro l i f e ra t i ve an d lym p h op ro l i f e ra t i ve d iseases wa s d on e in Tasm a n ia, Au s t ra lia , with d ata fro m 1972 to 1980. Within that p op ulation there we re 798 to-tal cases, in clud in g 241 NHL (125 m ale an d 116 fem ale). Th e con trol grou p was selected , based on a 1:1 ra t i o. In d ivid u a ls we re m a in ly asked fo r b ot h oc cu p ation a l an d fam ilia l h ist ori e s. Based on a few cases, it was seen a stron g asso-ciatio n b etwee n m a le fou n d r y worke r s an d N H L , OR = 8.0 (1.07- 356.0). T h e re we re five ex-p o se d c ases a n d n o exex-p o sed con tr o ls am on g fem a le h aird resser s (Sm ith & Lic kiss, 1980; Giles et al., 1984).
A p o p u lat ion - b ased c ase - con tro l stu d y e va lu ated en viro n m en tal ch e m ical exp osu re s as r isk fact ors for leu kem ia an d N HL (Eve re t t et al., 1985). Th e selec ted su b je cts we re 1,200
m en with t h ese d isea ses an d c on trols by ra n -do m d ialin g an d from so cial secu rity files. Ex-p o s u re evalu ation in clu d ed a series o f ch em i-cals wh ich are seen in th e workp lace or h om e. For NHL, th e followin g od d s ra tio we re n oted for solve n t re late d e xp osu re s: la cq u e rs/ va r -n i s h e s, OR = 1.24 (p < 0.1); e-n gi-n e exh au st, O R = 1.26 (p <0.05); h yd ro carb on c oat s, OR = 1.67 (p <0.1); h yd ro ca r b on clea n e rs, OR = 2.13 (p <0.001); p a in t a ero s o l s, OR = 1.28 (p < 0.1) an d ga so lin e a s a c lea n in g age n t , OR = 1 .29 ( p < 0 . 0 5 ) .
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A death certificate-based case-con trol s t u d y of NHL an d occu pation s with 501 an d 569 m ale c ases a n d co n tro l s, re s p e c t i ve l y, was c ar ri e d ou t in No r th Ca r olin a (Sch u m ach er & De l ze l l , 1988). Th ey ob ser ved a n in c rea sed risk for o c-c up at ion s in ru b b e r, p lastic-cs an d syn th et ic-cs’ i n d u s t ries on ly fo r wh ite s, b a se d on fo u r e x-p osed cases an d n o exx-p osed con tro l s. Associa-tion s we re n eith er see n for o ccu p a Associa-tion s with p o te n tia l b en ze n e exp osu re n or for c h em ica l d ru gs an d pain t in d ustri e s.
Two hu n dred an d two m ale cases (ICD 200-202), age 20 a n d over a n d 666 age m atc h e d m ale co n tro l s, exc lu d in g sm oker ela ted can -c ers an d p rost at e -c an -ce r we re sele -ct ed fr o m Mi s s o u ri Ca n c er Re g i s t ry b e twee n 1984 a n d 1985. Risk excess was foun d on ly am on g p ri n t-e r s, OR = 2.72 (0.96-7.69). No association s wt-e rt-e o b s e r ve d with ot h e r solve n t rela te d o ccu p a -tion s (Brown son & Reif, 1988).
An other Swed ish study was specifically de-sign e d t o in vestiga te th e r isk of N HL am on g m e n oc cu p at ion ally exp o se d to o rga n ic so l-ve n t s. It wa s a h osp it al-b ased case-c on t ro l s t u d y, wh ere the case grou p was p erf o rm ed by a c on secu tive series of 167 m en a d m itte d b e-t ween 1978- 1981, in e-th e De p a re-tm en e-t of On c o l-o g y, Un i versity Hl-osp ital l-of Lun d (Swed en ) an d th e con trol grou p by 130 health y m en selected f rom th e p opu lation re g i s t ry. Ex p o s u re was de-fin ed by “han dlin g organ ic solven ts for at least on e year daily”. Ca t e g o rization in five yea r age g rou p s showe d an ORM-H = 3.3 (1.9-5.8); fo r s u p ra - d i a p h ragm atic tu m o rs, OR = 6.5 (3.2-13.3) a n d for ot he r lym p h o m a p re s e n t a t i o n s, OR = 2.3 (1.3-4.3) (Olsson & Bran d t, 1988).
In Ha n coc k Co u n t y, Oh i o, all wh it e m ale resid en ts aged 15 o r m o re w ho d ie d d u ri n g 19581983 with m align an t lym p h om a we re en -r olle d in a c ase-c on t -rol st u d y. T h e -re we -re 61 NHL an d 15 HD, who we re m atched with other d eceased in d ividu als, ch osen through a stra t i-fied ran dom sam p le by age at death an d year of d eath , in a p ro p o r tio n o f 4:1. No asso ciat ion s we re foun d with solve n t - related occupation s or i n d u s t ri e s. In ad d ition , with th e sm all n um be r of sub je ct s a n d d esp it e t h e ru sh to co m p let e s t u d y, the au th ors d iscu ssed th e lim itation s of su c h a d ea th c er t ific ate- b a sed case-c on t ro l s t u d y, m ain ly b ecause of the in accuracies in th e cause of death an d the lack of occup ation al an d i n d u s t rial in form ation (Du b row et al., 1988).
All wh ite U.S. Navy e n listed m en d u ri n g 1974-1983 we re th e su b jec ts of a lar ge coh or t st u d y (Ga rlan d et al., 1988). Th e u n exp o se d g ro u p was p e rf o rm ed by t he U .S. p o p u la tio n p rovid ed by SEER (Su rve i l l a n c e, Ep i d e m i o l o g y, an d En d Resu lts). The exp osed grou p was com
-p osed of 435,425 m en / 3,704,864 -p erson / ye a r s f rom 80 U.S. Navy occup ation s. Th e NH L cases we re re v i e we d by a b oa rd o f sp e cialist s a n d c la ssified a cco rd in g t o th e ICD 8th : (200.0, 200.1, 202.0-202.9); ICD 9th : 200.0, 200.1, 202.1, 202.8, 202.9. Sixty eigh t NHL cases we re fou n d in th e exp osed gro u p. T h e re we re five ca se s am on g aviation stru c t u ral m echan ics, stan dard in cid en ce ratio (SIR) = 1.5 (0.5-3.5) an d 1 case a m o n g m ac h in er y re p a i r m e n , SIR = 1.8 (0.0-1 0 . 0 ) .
A n ested case-con trol stu dy was con du cted with in a coh or t o f 29,139 em p loyed m en fro m t wo ch em ic a l p lan t s b et ween 1940 an d 1978 ( Ott et al., 1989). Th e au th ors we re lo okin g for
lym p h atic a n d h em a top o iet ic tissu e ca n ce rs, an d am on g all cases (129), 52 we re iden tifie d as N HL fr om b oth u n d er lyin g an d con tri b u t o ry ca u ses of d eath . Co n t r ols we re se lec ted fro m t he tot al e m p loye e c oh ort acc ord in g to a g roup -m atch ed in ciden ce den sity sam p lin g in a 5:1 ra t i o. El e va te d o d d s rat ios we r e see n in t h e eth a n ol u n it , OR = 5.4 (1.5-19.5) b ased in f i ve cases, an d in two m a in t en a n ce a n d c on -s t r uction gro u p -s, forem en an d oth er-s, 11 ca-se-s, OR = 3.2 (1.4-7.2) a n d in str u m e n t m e n , OR = 5.2 (1-26.7), th ree cases. Th e authors discu ssed th e role of th e carcin ogen ic action of alkyl su l-fat es wh ich or igin at ed fr o m th e rea ctio n b e-t ween a lken es a n d su lfu ric a cid e-to p ro d u c e eth an ol an d isop rop a n o l. They also d iscu ssed t h e d ifficu ltie s in e xp lain in g th e fin d in gs a m o n g fo rem en a n d oth er s b eca u se o f th eir h e t e rogen eit y an d th e la ck of tren d s with em -p l oym en t du ration . Th e authors fou n d an OR = 1.2 (two exp osed cases) for less th an five ye a r s an d an OR = 1.6 (three exp osed cases) for m o re th an five years of exp osu re.
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1.01 (0.46-2.23); b en ze n e / s o l ve n t s, OR = 1.14 (0.57- 2.28) an d woo d / fu rn i t u re, OR = 0.66 (0.37- 1.19) (Fran cesch i e t al., 1989).
An other Italia n stu d y d id n ot sh ow an y as-sociation between NHL an d a group of selected s o l ven t related occup ation s an d agen ts (ch em -ical, p e tr oc h e m ica l p lastic re s i n s / g l u e s, sol-ve n t s / b e n ze n e, oil, dye s / p a i n t s, ru b b e r, p ri n t-in g an d fu r n i t u re ). It wa s a h o sp it al-b ased c a s e - c o n t rol stu d y which in clu d ed 153 in c i-d e n t c ases o f NHL (93 m a le s an i-d 60 fe m ales), 69 Ho d g k i n’s disease a n d 110 m u ltip le m ye l o-m a d iagn osed in p atien ts aged 15-74, ado-m itted to a n etwork of teach in g an d gen eral h osp itals in th e grea te r Milan a rea , fr o m 1983 to 1988. Co n t r ols we re 396 p at ien t s a d m itt ed t o th e sa m e h osp itals with ac u te con d ition s (La Ve c-ch ia et al., 1989).
Da ta fro m a p reviou sly select ed c o n tro l g rou p for t wo o th er stu d ies, from th e p op ulation re g i s t ry, we re u tilized in a n ew c ase con -t rol s-tu dy (Persson e-t al., 1989). Cases we re 106
NHL (66 m en an d 40 wom en ) an d 54 HD cases, ob tain ed from th e De p a rtm en t of On cology at Ö reb o Medical Ce n t re Hosp ital, Swed en . T h e y we re d iagn osed b et ween 1964 a n d 1986, a n d we re still alive in 1986, ran gin g in age from 20-80 ye a r s. Bot h gr ou p s a n swe red p osted q u e s-t i o n n a i re s. In s-this h osp is-tal-based c ase- con s-tro l s t u d y, so lven t exp osu re wa s c lassified by five l e vels of in ten sity, fo r at least o n e ye a r, takin g in t o co n sid eration a laten c y t im e of five t o 45 years before diagn osis an d tim e of selection for c o n t ro l s. T h e re we re seen som e im p ortan t in -c reased r isks: solve n t s, OR = 2.0 (33/ 50 exposed c a s e s / c o n t rols); thin ner, OR = 2.7 (15/ 16); w h i t e s p i rit, OR = 3.1 (13/ 12); tri c h l o ro e t h y l e n e, OR = 1.5 (8/ 14); styre n e, OR = 8.0 (3/ 1); p ain ters, OR = (3/ 0); p lastic / ru b b er ch em ica ls, OR = 2.5 (9/ 10); ca rp e n te r/ ca b in e t m akers, OR = 3.1 (10/ 9). The con fiden ce in tervals we re n ot cited . The logistic OR = 1.9 (90% 1.1-3.2) an d OR = 2.8 (90% 1.1-7.1) ap p ly to solven t exp osu re to car-p en ters an d cab in et m akers, re s car-p e c t i ve l y.
A n ew stud y was con ducted (Persson et al., 1993) wit h th e sa m e p la n n in g. Cases we re 93 N HL a n d 31 HD occ u rred in m e n livin g in Ö s t e rgötlan d, Jön köp in g an d Kalm ar cou n ties, ob tain ed from the Region al Can cer Re g i s t ry at t h e Un i ve rsity Ho sp ita l in Lin köp in g, d iag-n o se d b etwe eiag-n 1975 aiag-n d 1984, alive iiag-n 1986, a n d a ged 20-80. At th is t im e, o n ly m en we re stu d ie d . Two h u n d red an d fou r re f e re n t in d i-vid u a ls we re d rawn fr om t h e p o p u latio n re g-i s t r y. In th a t st ud y, oc c u p at g-io n al e xp o sure t o s o l ven t s re ve ale d an OR = 1.2 (28/ 53 e xp osed ca ses/ e xp osed c on t ro ls) a n d a n OR = 1.7 a n d an ORlog = 1.1 (0.6-2.2) (24/ 34), when in ten sity
c a t e g o ry levels 2-5 X 0- 1 we re an alyzed ; white s p i ri t , OR = 1.6 (14/ 20); aviation gasolin e, OR = 3.0 (4/ 3). For n o n -oc cu p ation al exp osu re was seen an OR = 3.4 (3/ 2). Carp en ters an d cab in et m a kers h a d an OR = 1.0 a n d a n ORlog = 0.9 (0.4-2.1) (11/ 25), which m ean s a con flictin g re-su lt in re g a rd s to th e form er in ve s t i g a t i o n .
A p op u lation -b ased case -con trol stu dy was p ri m a rily design ed for lookin g for association s b e t ween NH L o cc u rren c e an d sp ecific agen ts in farm p ra c t i c e s. Cases we re 201 m en aged 21 or olde r in 66 cou n ties of eastern Ne b raska, di-agn osed with N HL fro m 1983 to 1986. T h e y we re id e n tifie d th rou gh th e Ne b ra ska Ly m -p h om a St u d y Grou -p Re g i s t r y a n d are a h os-p i-tals an d ph ysician s, an d re v i e wed by a p atholo-gist. Co n t rols we re 725 su b jects se lected fro m resid e n ts of th e sa m e area, m at ch ed by a ge, ra ce an d vita l sta tu s. Bot h gro u p s we re in te r -v i e we d by tele p h on e. Fo r exp osur e to c hlor i-n a ted h yd r oca rb oi-n s ai-n OR = 1.9 (0.8- 2.3) was o b s e rved (We i s e n b u rger et al.,1990).
Th e rela tion sh ip of occu p a tion a l r isks an d hem atological m align an cies d evelop m en t we re e valu ate d thr ou gh a h o sp italb ased case con -t rol s-tud y (Pasq uale-t-ti e-t al., 1991). Th ey selec-t- selected 108 N HL with in 620 n eop lasm h osp ital p a -tien ts aged 24-85, an d 2:1 sex an d age m atch ed h o sp ita l c on t ro ls with “m ed ical d isea ses”, ex-cep t can cer a n d con gen ital d isea ses, from th e sam e area as th e ca se s. On o n e h an d , th e au th ors fou n d sta tistica lly sign ifican t asso cia -tion s b etween h em atolo gical m align a n cies in g e n e ra l a n d in d u st r ial a ct ivitie s, OR = 2.97 (1.98-4.46), exp o su re to ar om a tic hyd ro c a r-b o n s, OR = 2.15 (1.39-3.32), d yes an d in ks, OR = 1.28 (1.11-1.99), m in eral oils, OR = 2.59 (1.75-3.84) an d p ain ts an d re lat ed p ro d u c t s, OR = 1.55 (1.06-2.26). On th e oth er h an d , wh en they a n a l y zed sp ec ifica lly th e N HL su b se t, on ly a n asso c ia tio n with m in e ra l o ils wa s seen , OR = 3.4 (1.65-7.38). They h ave fou n d a lack of assciation between NHL an d other p oten tial exp o-s u reo-s to o-solven to-s o-such ao-s au to m echan ico-s, ra i l-road work e r s, or specific exp osu res to ceton as, alip h atic hyd ro c a r b o n s, ch lorin ated h yd ro c a r-b o n s, an d dye, p ain ts an d in ks.
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m ain ly in th e fin din gs of wood workin g (m ale), RR = 1.15 (0.87-1.52); ch em ists (fem ale), RR = 2.32 (0.85-5.04) an d haird ressers (fem ale), RR = 2.01 (0.81-4.14).
In c id e n t c ases o f NHL (572) an d leu kem ia (520) am o n g wh ite m en d ia gn osed b etwe e n 1980 an d 1983 in Iowa an d Min n esota we re se -lec te d fo r a p op u la tion -b ased c ase- con t ro l stu dy in th e USA (Lin os et al., 1991). Di a g n o s e s we re re v i e wed b y a p an el of p ath ologists. Co n -t rols we re fre q u e n c y-m a-tch ed by year of bir-t h , vit al st at u s, sta te o f re sid en ce a n d year of death, b y a two-stage ran dom d igit d ialin g (<65 years) an d from Health Ca re Fin an ce Ad m i n i s-t ras-tion (65 years). Qu e s s-t i o n n a i res we re ap p lied to st ud y sub jects or the ir n ext -o f-kin , an d e x-p o s u re was defin ed as th e location of re s i d e n c e with in 3.2 an d with in 0.8 Km from a fa ct or y. Am on g the fir st on es, we re factories whe re or-gan ic so lven t s ar e h an d led . In th e ch e m ic a l p la n t t h ere we re 18 EC, RR = 1.0 (0.6-1.9), in th e p et role u m in d u st r y, 14 EC, RR = 1.5 (0.7-3.2) an d in t h e r u b b e r p la n t , 11 EC, RR = 0.6 ( 0 . 3 - 1 . 3 ) .
In an ec olo gica l stu d y, in fo rm a tion ab o u t lym ph o-h em atop oietic n eoplasm in ciden ce in 22 coun ties in the UK (1984/ 1988) was cro s s e d to ca r own ersh ip b y co un ty (1981) from Gre a t Br itain Pop u latio n Cen su s a n d Tra n s p o rt St a-tist ics d a ta. T h e re we re 2,415 low grad e a n d 2,550 h igh gra d e NH L with in a to tal of 21,072 n e o p l a s m s. The Sp e a rm an ran k correlation co-efficien ts sh owed a sta tistica lly sign ifican t as-so c ia tion b et ween low grad e NHL in c id en c e an d c ar s p er h o useh o ld (0.66 p < 0.001) an d cars p er th ou san ds (0.68 p <0.001). No associa-tio n was seen for h igh gra d e NHL. Th e au th or called for re s e rvation ab ou t th ese p re l i m i n a ry ou tc om es from d a ta b ased on ge ogra p h i c a l c o r relation , b u t im p lied th at if th e se are tru e, th e n on -occup ation al low exp osu re to b en ze n e f ro m p e tr ol c om b u st ion a n d p e trol eva p o ra-tion m ay b e p la yin g a n im p orta n t role (Wo l f f , 1 9 9 2 ) .
A h osp ital-based case-con trol study, where cases we re all n ewly N HL d iagn osed p atien ts, f rom 1980 to 1982 was c arried ou t am on g re s i-d en t s o f t h e Bo st on Me t r op olita n Ar ea wh o we re treated in on e of n in e p articip atin g hospi-tals (Sche rr et al., 1992). The con trol grou p was com p osed of in d ividu als m atched by age, sex, t own an d p re cin ct of re s i d e n c e, r an d om ly se-lected from th e town residen ce list. Cases we re m a d e u p of 152 m ale s an d 151 fem ales, with c o n t r ols for t he 303 in d ivid u als. Di a g n o s e s we re re v i e wed by a p an el of p ath ologists, wh o u t i l i zed Ra p p a p o rt (m od ified ) an d In t e rn a t i o n -al Wo rkin g Fo r m u lat io n NH L classific ation s.
Qu e s t i o n n a i res we re d ire ctly ap p lied to c ases (67%), to cases’ p roxies (31%) an d t o cases’ g u a rdian s (2%). No in form ation was m ent i o n e d re g a rd in g distribution of these in ter views with-in th e con trol gro u p. Th e m a with-in re s u l t s, re l a t e d to solven t exp osures were: gasolin e or k e ro s e n e, OR = 1.0 (0.6- 1.7); b en ze n e, OR = 1.2 (0.5-2.6); c h o r in a te d solve n t s, OR = 1.2 (0.8-1.8); m et al i n d u s t r y, OR = 1.2 (0.6- 2.5); m ach in er y, OR = 0.8 (0.4-1.4); sh ip bu ild in g, auto, OR = 1.0 (0.6-1.7); chem icals, dr ugs an d p ain ts, OR = 0.3 (0.1-0.9); leat h e r, OR = 2.1 (0.9-4.8); d r y c lea n in g, OR = 1.6 (0.6- 4.0); p ain ter a n d p lastere r, OR = 6.0 (0.9-38); carp en ter, brick an d ston e m ason , p lu m b e r a n d ro o f e r, OR = 12.0 (2.0-72); air-p lan e or au to m echan ic, gas station a t t e n d a n t , OR = 1.4 (0.6-3.6).
Can c er in cid en ce fr o m 1971 to 1984 was d e fin ed u sin g th e Swed ish Ca n c e r En v i ro n -m en t Re g i s t ry, with occu p ation al in for-m a t i o n f rom th e 1970 cen sus (Eriksson et al., 1992). At th e en d o f th e follow u p th e au th o rs got 1,082 NHL cases (830 m en 252 wom en ), 317 HD an d 684 MM classifie d a cco rd in g t h e ICD 7th 200-203. Am o n g a ll oc cu p a tion a l grou p s wit h p o-t en o-tial e xp osu re o-to so lve n o-t s, carp en o-te rs (149 OC) yie ld ed a SIR = 1.2 (1.0-1.5).
A n este d ca se -c o n tro l stu d y wa s carr i e d o u t w it h fa t al lym p h at ic a n d h e m a top oiet ic m align an cies which occu rred in m ale work e r s o f eigh t No r th Am er ica n styre n e - b u t a d i e n e p lan ts b etween 1943-1982. Th e origin al cohor t h ad 13,686 workers an d yield ed 15 N HL c ases am on g 59 lym p h oh em a top oietic ca n c ers. T h e c o n t rol grou p was p erf o rm ed by 193 in d ividu -a l s, m -atch ed by ye-ar of h ire, d -ate of d e -ath , -age a n d d u ration o f wo rk, selected fro m th e sa m e c o h o rt with c au ses of d e at h oth er th a n n e op l a s m s. A job exop osu re m atrix ( JEM) was c on -s t ruc ted by a p an el of fou r ch em ical en gin eer-s wh o classified t he exp o su re to styr en e a n d t o b u t a d ien e u sin g d at a from p er son a l re c o rd s. For styren e exp osu re an OR = 1.39 (0.13- 3.92) was seen for lym p h osarcom a an d an OR = 2.42 (0.50 11.6) fo r o t he r lym p h o m a s, wh ic h in -c lu d e m ye lom a (Sa n t o s - Bu rgo a et a l., 1992).
Ep id em iologic stu d ies p er tain in g to th e p ossb le re la tion ossb et wee n exp osu re to 1,3-ossb u ta d i-e n i-e a n d t h i-e o cc u rr i-en c i-e o f lym p h at ic a n d h em atop oietic can cer am on g styre n e - b u t a d i-en e r ubb er an d b utad ii-en e p rod uction work e r s we re re v i e wed . In th e a ggregat e d at a, the re we re 20 observed v s .17.9 exp ected death s fro m l y m p h o s a rcom a c ase s. In gen eral, it was con -clu ded th at th ere is n o su p p or t for a cau sal re-lation ship for su ch exp osures (Cole et al., 1993).
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1993). Cases we re m a lign an t lym p h om as an d leu kem ia s n otified to th e Fin n ish Ca n cer Re g-i s t r y, d g-ia gn o se d g-in m a le wo od wor ke r s of 35 p l a n t s, with in a c oh or t of 7,307 work e r s, b e-t ween 1957-1982. Co n e-t rols (52 for e-the NHL cas-e s) wcas-e r cas-e m a tc h cas-e d b y ycas-ear o f b ir th a n d su r-v i r-va l / n o n - s u rr-v i r-val statu s in 1983, selected fro m t h e sam e coh or t. On ly e igh t N HL c ases we r e fou n d (ICD 200, 202). In d ivid u al exp osu res to s o l ven ts an d to oth er agen ts we re re c o n s t ru c t-e d u sin g a p la n t/ p t-eriod -sp t-ecific JEM (cast-e s an d con trols). Also in terviews of p erson s at th e p la n ts we re p er f o rm ed a n d q u estion n aire s we re ap p lied (on ly to ca se s or th eir n e xt-o f-kin ). For u n id en tified so lve n t s, leukem ias an d lym p h om as p oo le d (fo u r exp ose d cases) p r o-d uceo-d an OR = 5.62 (0.99- 32.0) an o-d ao-d justm en t for fo rm a l d e h yd e exp o su re sh owe d an OR = 5.07 (0.40- 63.5). Two exp osed cases an d n o ex-p osed con trols we re seen wh en NHL we re an a-l y zed sep ara t e a-l y.
Wh ite m en with NHL re p o r te d to the Iow a Sta te Healt h Re g i s t ry, b e tween 1981 to 1983 an d b etween 1980 to 1982 at a n etwork of hos-p itals in Min n esota we re in clud ed in a hos-p ohos-pu la-t io n -b ased c ase- con la-tro l sla-tu d y (Blair e la-t a l.,
1993). Th e 1,245 con trol in d ivid u als we re fre-q u en c y m at ch ed with th e 622 NHL ca ses by a g e, year of d eath for d eceased cases, an d state, f rom ran d om d igit d ialin g, m ed ica re files an d listin gs of d eath. Qu e s t i o n n a i res we re d ire c t l y a p p lied t o c ases a n d c on t rols or t h eir su rro-gates an d in clud ed in for m ation ab ou t job titles a n d in d ustri e s, which we re fu r th er eva l u a t e d b y a n i n d u s t rial h ygien ist, wh o d ecid ed th e p ro b a b i l ity of exp osure (fou r levels) an d in te n sity of exp osu re (three levels). The au th ors con -clu d ed th at in d u str ial exp osu res are n ot a m a-jor c on t rib u tor to t h e etiology o f NHL. So m e i m p o rtan t fin din gs we re: p ain tin g/ pap er han g-in g, O R = 1.9 (0 .9 -3 .8 ); p e t r ole u m re f i n i n g , O R = 1.6 (0.5-5.8); p r in tin g, OR = 1.5 (0.4-5.1); p a i n t s, OR = 1.1 (0.9-1.5); asp h alt an d cre o s o t e, OR = 1.0 (0.7-1.6); gasolin e an d diesel exh austs, OR = 1.0 (0.8-1.3). Th is stu d y tried to fin d a re-la tion ship b et ween low an d high e xp osu re s an d su b-types of the disease, classified as follic-ular or d iffu se. It was seen th at th e risk of NHL rose sligh tly with in creasin g levels of exp osu re to ben zen e an d oth er solve n t s. The m ain re s u l t s we re: ben ze n e, OR = 1.1 1.4); OR = 1.3 (0.9-1.9) fo r low leve l / f o l l i c u l a r; OR = 1.9 (0.7-5.3) for high/ follicular; OR = 1.2 (0.8-1.8) for l ow / d i f-fuse; OR = 1.8 (0.6-5.4) for high/ diffu se; solve n t s oth er th an b en zen e OR = 0.9 (0.9-1.4); OR = 1.4 (0.9-2.0) for low / f o l l i c u l a r; OR = 1.1 (0.4- 2.7) for h i g h / f o l l i c u l a r; OR = 1.0 (0.7-1.5) fo r low / d i f-fu se an d OR = 2.4 (1.2-5.0) for h igh/ d iff-fu se.
A lar ge c oh ort stu d y lin ke d in fo rm a t i o n ab ou t can cer in c id en ce from 1961 to 1979 us-in g the Swed ish Ca n c e r- En v i ron m en t Re g i s t ry with o ccu p ation al in form ation fr om th e 1960 cen su s (Lin et et al., 1993). T h e re we re 4,496 ob -s e r ved ca-se-s am on g em p loye d Swed i-sh m e n d i s t ributed am on g in d ustrial an d occu pation al c a t e g o ri e s, wh ic h d er i ve d fro m in t ern a t i o n a l s t a n d a rd s. Th e m ost im p or tan t association s re-g a rd in re-g solven t exp osure we re seen in the sh oe repair in dustry: 23 cases, SIR = 1.8 p <0.05; s h o e-m akers: 23 cases, SIR = 1.7 (p <0.05); p orc e l a i n an d ea rt h e n w a re: 14 ca ses, SIR = 1.9 (p <0.05); f u rn i t u re m aker : 44 cases, SIR = 1.3 (p <0.01) an d lorr y d r i vers: 42 cases, SIR = 1.4 (p <0.01). Ot he r well kn own solve n t relate d in d u stri e s an d occu p ation s failed to sh ow association s.
Th e sam e strategy was ap plied to stu d y th e fem a le wor ke r s (Lin et et al., 1994). Th ey ob
-s e rved 1,174 ca-se-s of NHL in em p loyed Swe d i -s h wom en . At th at tim e, the followin g resu lts we re ve rified : fu rn i t u re a n d fin ish in g in d u stry: fou r c a s e s, SIR = 1.5; grap hics in d ustry an d p ub lish -in g b uin ess: 15 cases, SIR = 0.7; ru b ber -in d u s-t r y: five cases, SIR = 1.1; ch e m ical in d uss-tr y: n in e ca ses, SIR = 0.8; m ach in e an d electro n i c s i n d u s t ry: 26 ca ses, SIR = 0.8; sh oe an d leath er w o rkers: 10 cases, SIR = 1.4.
A death certificate-b ased case-con trol s t u d y ( Ma ssou d i, 1994; Masso ud i et al., 1997) wa s
don e in Kan awh a Cou n ty (West Vi rgin ia). Ca s-es we re 435 lym p h atic an d h em atop oietic n e o-p lasm s in wh it e m ale aged 23- 96 wh o h ad d ie d b e t ween 1965- 1990. Am on g th em th e re we re 106 NHL (ICD 9th 200, 202) re v i e wed by a p ath o lo gist. In d u s t rie s an d occu p at ion s we re ob tain ed from d eath certificates an d va l i d a t e d by in ter viewin g n ext -o f-kin . T h ree ca tegor i e s of exp osu re we re d efin ed : ch em ic al m an u fac -t u r in g work e r s, -th ose exp o sed -to ch em icals a-t other job s, an d those n ot exp osed. Th e associa-tion between NHL an d work in ch em ical in du s-t ries wa s an a lyzed (c h em ic al wor ker s ve r s u s n ot exp osed ): c ru d e a n alysis, OR = 1.52 (0.8-2.8); a ge <65 OR = 3.11 (1.1-8.8); age 65 OR = 0.97 (0.5- 2.1).
An oth e r large co h or t stu dy wa s d eve l o p e d in D e n m a rk (Ko lst a d et a l., 1994). Th e e
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180, 88 an d 43 p p m (1,814 we re sam p led fro m com p an ies in clu d ed in th e stu d y). Am on g th e com p an ie s wit h 149 % o f wo rkers in re i n -f o rced p lastics p rod uction the -followin g re s u l t s we re seen : < 10 years sin ce 1st em p loym en t: 19 o b s e r ved ca ses (OC), SIR = 2.35 (1.42- 3.67); 10 year s: 17 OC, SIR = 1.23 (0.71-1.98). Am on g th ose c om p a n ies with 50-100 % o f worke rs in re i n f o rced p lastics p rod uction d ifferen t re s u l t s we re fou n d: <10 years sin ce 1st em p loym en t: 2 OC, SIR = 0.43 (0.05-1.57); 10 year s: fo u r OC, SIR = 0.79 (0.22-2.02). Wh en a ll co m p a n ies we re evalu ate d t ogeth er, SIR wa s 1.33 (0.96-1.80) with 42 OC. Th e a n alysis p e r ye ar of th e 1st em p loym en t did n ot sh ow sign ifican t fin d -in gs: 1964-1970, 21 OC, SIR = 1.28 (0.79-1.96); 1971-1975, 10 SIR = 1.19 (0.57-2.18); 1976-1988, 11 OC, SIR = 1.64 (0.82-2.94).
Based on d eath cert i f i c a t e s, a ca se-c on tro l stu dy whe re cases we re 23,890 NHL deaths was don e am on g residen ts from 24 Am erican states b e t ween 1984-1989 (Figgs et al., 1995). T h e re we re five n on -can cer d ea th con tr ols p er ca se, totalin g 119,450 in d ivid u als. Cases we re classi-fied a cco rd in g to th e ICD 9th , cat ego ries 200 an d 202 (except 202.3 an d 202.6). Ex p o s u re was d efin e d as in d u stries an d oc cu p at ion s o b -ta in e d fro m d e ath cer t i f i c a t e s. Oc c u p a t i o n s with c ertain or p ot en t ial exp o sure to solve n t s we re stratified for ra c e. For white m en , airc ra f t m ech an ics had an OR = 2.5 (1.1-6.0) with eight exp o sed c ases; far m eq u ip m en t m ec h an ics, s e ven exp osed ca ses, OR = 2.1 (0.9-5.3); elec-t ron ic re p a i r s, 12 exp osed cases, OR = 2.1 (1.1-4.1); m iscellan eous electron ic an d electrical re-p a i r s, 10 exre-p o se d c ases, OR = 2.0 (1.0- 4.3); p a i n t e r s, 65 exp osed ca ses, OR = 0.6 (0.5-0.8). For black m en , on ly sh ip / boat b uild in g an d re-p air in d u str y was im re-p or tan t in relation to sol-ven t exp o su re an d h ad sesol-ven exp osed cases an d an OR = 2.9 (1.1- 7.9).
A casecon trol study in Lyon , Fra n c e, eva l u -at ed c ases o f h em a tolo gical m a lign a n cies, wh ich in clud ed 52 NHL of both sexes, aged 30-74 a n d d ia gn osed b et we en Ja n u a r y/ 1981 a n d Decem b er / 1987 in two h osp itals (Hours et a l., 1995). Co n t r ol sub jects we re n o n - can c er an d n on - oc cu p a tion a lly d isea sed p at ien t s, 1:1 m atch e d by sex, a ge an d n at ion ality, fr om th e sam e h osp itals. Oc cup ation al exp osu re to 320 com p ou n d s wa s ve rified u sin g q u estion n a ire s p lus evaluation by experts in che m istry an d oc-cu p at io n al m e d ic in e. An OR = 2.1 (p = 0.23) b ased on 13 exp o sed c ases was seen for e xp o-s u re t o m on o n u clear a ro m atic h yd ro c a r b o n o-s which in clude ben ze n e. An OR = 14.86 (p < 0 . 0 1 ) was fo u n d fo r e xp o su re to a m ixt ure of b en -ze n e, tolu en e an d xylen e (BTX) based in six
ex-p osed c a se s. Po lyn u clear aro m atic h yd ro c a r-b o n ha d (30 EC), OR = 0.76. Ex p o s u re to in ks (20 EC) yielded an OR = 2.47 (p = 0.02) an d va r-n ish ar-n d p air-n ts exp osu re (six EC), OR = 2.55 (p = 0.08).
In a sm all coh ort m ortality stu d y, 338 m ale e m p l oyees (3,813 p / y) of the fleet m ain ten an ce d ivisio n of th e D C’s De p a r tm en t o f Pu b l i c Wo rks (DPW ), em p loyed fo r at le ast o n e ye a r b e t ween 1977-1991 we re followed u p (Hu n t i n g et al., 1995). Nin e can cers an d three lym p h atic a n d h em a top o iet ic d e at h s (on e N HL d ea th ) we re fou n d . Pote n tial e xp osu re to fu e ls a n d s o l ven ts was classified as low, m ed ium or h igh , a c c o rd in g to p erso n a l re c o rd s d at a an d DPW a n d u n ion re p re s e n t a t i ves d isc u ssion . T h e t h re e lym p h a tic an d h em at op oietic can ce rs s h owed a SMR = 4.22 (0.87-12.34) an d the NHL c a s e, a SMR = 2.57 (0.06-14-27).
A ve ry large m ulticen ter re t ro s p e c t i ve stu dy was co n d u c te d with in a c oh o rt of Ch in ese w o r ke rs (Dose m e ci et al., 1994; Tr avis et al., 1994;Yin et al., 1996). Th e exp osed gr ou p was c om p osed of 74,828 wo rkers e m p loyed fro m 1972 to 1987 in 672 fac to ries in 12 Ch in ese c ities an d th e u n exp osed we re 35,805 work e r s f ro m 109 fa cto r ie s in t he sam e p e rio d a n d p l a c e s. Th ey an a lyzed all availa b le d ata : work u n it s; job titles; m on ito rin g d ata ; list of row m a t e rial an d fac to ry p ro d u ct s; e n gin e eri n g c o n t ro l; p e rso n al p ro t e c t i ve eq u ip m e n t an d with them , b en zen e exp osure in p arts p er m il-lion was estim ated . Se ven teen exposed d eaths, RR = 4.5 (1.3-28.4) an d 20 exp osed cases, RR = 3.5 (1.314.9) we re foun d . In th is stud y, the lim -itation was the lack of h om ogen eity of the data f rom too m an y d ifferen t p lan ts.
In a n est ed c a se - co n tr ol stu d y in Ca n a d a , c ases we re all m a le NHL d eath s from a c oh ort of p etroleu m workers an d con trols we re select-ed from the sam e coh ort m atch select-ed by a decad e of bir th in a p ro p o rtion of 4:1 (Sch n atter et al., 1996). Of a total of 31 lym p h o-h aem atop oietic c a n c e r s, eight we re NHL. Person al re c o rds p lu s e va lu a tion by exp e rts in in d u st r ial h ygien e we re u tilized to estim ate b en zen e an d th e total h yd rocarbon exposu res in pp m . No association was foun d between the low level exp osures an d m o rtality by NHL. Th e size an d con sequ en tial-ly th e p ower of th is stu d y we re seen as im p or-tan t lim itation s.
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t ween 1979-1985 an d resid in g in Mo n t real. T h e c o n t rol grou p con sisted of 2,357 oth er can cer p a t i e n t s, exclud in g lu n g can cer, an d by 533 in -d ivi-d u als sele ct e-d fr o m a n elec tor al list or by ran d om d igit d ia lin g. A stru c t u re d q u estion -n a i r e p lu s eva lu a tio-n by a te am of c h e m ist s a n d in d ustr ial h ygien ists we re u se d to d efin e e x p o s u re. Ex p o s u re wa s ca tegori zed as p ossi-b l e, p roossi-b aossi-b le an d d efin it e, an d th e fre q u e n c y o f exp osu re d efin ed a s <5%, 5-30% an d >30%. Th e con cen t ra tion o f th e age n t at th e wo r k-p lace was also an alyzed . These th ree m easu re s we re com bin ed, p rod ucin g th ree grou p s: un p osed , n on -su b st an t ia l an d su b st an tia lly ex-p osed . Occu ex-p at ion s a n d in d u st r ie s we re also c la ssified . No a sso ciat io n was fo un d . T h e re we re 20 cases e xp o se d t o b en zen e an d cla ssi-fied as th e n on -sub stan tial exp osed gro u p, OR = 0.7 (0.4-1.1) a n d six in th e su b st an tial ex-p osed gro u ex-p, OR = 0.8 (0.3-2.1). For solven ts in g e n e ral, cla ssified a s low le vel, th ere we re 26 EC, OR = 0.6 (0.4-1.0) a n d for h igh level exp os u re, 48 EC, OR = 0.9 (0.6 1.3). Am on g ca rp en -t e r s, -th ere was n o case wi-th 1-9 yea rs of exp o-s u r e an d fo ur EC, OR = 0.8 (0.3- 2.2) fo r th oo-se with 10 years or m ore in th at occup ation . In th e f u rn i t u re in du stry: 1-9 ye a r s, on e EC, OR = 0.4 (0.1-3.4); 10 years or m o re: th ree EC, OR = 1.6 (0.4-6.1). Fi n a l l y, am on g the rub ber an d p lastic w o rkers: 1-9 years: four EC, OR = 3.6 (0.9-15.0); 10+ years: on e EC, OR = 9.0 (0.6-148.0).
Holly et al. (1997) developed a case-con tro l s t u d y. Cases we re 312 NHL am on g h om osexual m en , an d con trols we re also h om osexu al m en , m atched by age with in five years an d cou n ty of re s i d e n c e . Ch em ic al a n d oc cu p at io n al exp o-s u reo-s we re evaluated u o-sin g qu eo-stion n aire o-s. T h e a ut h o rs co n clu d e d th a t am on g th e H IV p osi-t i ve m en , occu p aosi-tion al exp osu res we re of bri e f d u ration an d d id n ot accou n t for the d eve l o p -m en t of th e NH L cases.
On e of th e m ost im p ortan t stu d ies was de -ve lo p e d b y Ta t h am et a l. (1997) u sin g d at a f r o m e igh t can ce r re g i s t r ie s in th e Un i t e d Stat es b etwe en 1984 a n d 1988. It wa s a p op u -lat ion - b a sed c ase - co n tr o l st u d y, wh ere th e 1,048 NHL cases in m en we re group ed by su b-typ es d efin ed by a p an el of p ath ologists. T h e re we re 185 sm a ll c e ll d iffu se lym p h o m as; 268 follicu lar lym p h om as an d 526 large cell d iffuse l y m p h o m a s. Co n t ro ls we re 1,659 in d ivid u als m at ch ed b y d at e of b ir th (within five ye a r s ) t h rou gh ran d om d igit d ialin g. All in d ivid u a ls we re in ter v i e wed by telep h o n e. Tim e of exp o-s u re for all jobo-s with kn own dateo-s we re defin ed within 10 years an d m ore than 10 ye a r s. An OR = 0.91 (0.75-1.10) was seen for c h lorin a ted h y-d ro c a r b o n s. For so lven t exp osu re, th e
follow-in g results we re fou n d : all NHL su b typ es, OR = 1.10 (0.90-1.30); sm all cell d iffu se, OR = 1.60 (1.10 2.20); sm all c ell d iffu se, 9 ye ar s of exp o -s u re, OR = 1.50 (0.99- 2.20); -sm all cell d iffu -se, > 9 years of exposu re, OR = 1.70 (1.10-2.60); sm all cell d iffu se, 10 years sin ce first exp osu re, OR = 3.00 (1.60-5.80); sm all c ell d iffu se, > 10 ye a r s sin c e first exp osu re, OR = 1.50 (1.00-2.10); fol-l i c u fol-l a r, OR = 1.0 (0.79-1.40); fol-lar ge cefol-lfol-l d iffuse, OR = 0.97 (0.79-1.20).
D i s c u s s i o n
In tota l, 45 stu d ies we re re v i e wed . Twen ty on e (46.7%) we re con d u cted in Eu ro p e. Th is issue was a con cern m ain ly in Swed en wh ere eight of th ese st u d ies we re d on e, in Italy five st u d ies an d fou r in th e Un ited Kin gd om . In No rt h A m e rica , 20 stu d ie s (44.4%) we re d o n e in t h e Un ited States an d two (4.4%) in Can a d a . T h e rem ain in g two stu dies cam e from Au s t ralia an d Chin a. On ly on e st ud y focu sed e xc l u s i vely o n wom en . In 25 stu d ies (55.5%) on ly m en we re se lec te d an d 19 (42.2%) in clu d ed b oth se xes. Th is d ifferen ce could b e p artially exp lain ed by th e fact th at m or e m ale worke rs h a ve a n op -p o r tu n it y t o b e ex-p osed t o orga n ic so lve n t s. Ne ve rt h e l e s s, m ost o cc u p ation a l c an c er e p i-d em io logic re s e a rch h a s foc u sei-d on wh ite m e n . Th e rea son s for exclu d in g wom en an d m i n o rities fro m co n sid e ra tion in t h is kin d of stud y are n u m erou s an d often legitim ate. Sm a l l n um bers of su bjects or eve n t s, lower exp osure s an d d ifficulty in tracin g we re the reason s m ost com m on ly given . Howe ve r, a gen eral lack of in -t e res-t or lack of con sidera-tion are also p ossible reason s (Zah m et al., 1994).
Sin ce th e ou tcom e of th ese stu dies is a ra re d i s e a s e, it was n ot a su rp rise th at the casecon -t rol d esign h ad b e en c h osen in 32 s-t ud ies (71.1%). Am o n g th em , h osp ita l b ased c a se -c o n t rol stu d ies we re m ost often -con d u-cted , 12 (37.5%), followed by th e p op u lation a l c a se c o n t rol d esign , n in e (28.1%), d eath cert i f i c a t e -b ased , fo u r (12.5%), n este d case-c on trol, fou r (12.5%) an d re g i s t ry-based case-con trol, th re e (9.4%). Oth er d esign s we r e 10 (22.2%) c oh or t s t u d i e s, t wo ec olo gic (4.4%) a n d on e clin ic al case series (2.2%). Th e n u m b er of cases ra n g e d f rom on e to 23,890 in divid uals.
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d isease wh ic h in c lu d ed a ll su b -typ es. T h re e stu d ies d ifferen tiated reticu lu m cell sa rc o m a s an d lym p ho sa rc o m a s, o n e stu d y c lassified it a c c o rd in g to th e seve rity of th e d isease as low or h igh gra d e. Two stud ies m ade th e distin ction b e t ween low an d h igh gra d e s, an d/ or differe n -tiated b et we en d iffu se an d fo llic u lar p attern s of t he tu m o r. In c om p arin g st u d ies wh ere p ath ologists re v i e wed slid es with stu d ie s h av-in g n o slide re v i e w, th ere was n o d ifferen ce be-t wee n be-t he re s u l be-t s. Th is issu e was be-t h e be-targ e be-t p o in t of a re view of 668 slid es of NHL, a n d an a g re em e n t o f 93% wa s ob ser ve d b etwe en r e-p o rte d d iagn osis a n d t h e e-p an e l re v i e w. It was con clu ded th at d ep en din g on the degree of p o-ten tial bias allowable in th e stu dy b ein g un der-take n , p a n el review t o co n firm d iagn oses of NHL m ay n ot b e n ecessary an d p an el review to d e velop su btyp es of NHL m ay n ot b e u seful in ep id em iologic stu dies, esp ecially re l a t i ve to th e tim e a n d c ost in vo l ved (D ick et al., 1987). As m e n tio n ed , m ost stu d ie s d id n o t u se t h e cu r -ren t classification system s to d iffe-ren tiate va ri-ous h istologies of NHL. On e reason for n ot u s-in g a detailed classification sch em e m ay b e th e s i ze of the stu dy that would b e re q u i red to h ave a su ffic ien t n um b er o f cases or even a fe w of the va riou s histologies th at wou ld achieve sta-tistical sign ifican ce for a twofold re l a t i ve risk or less (Sch err & Mu e l l e r, 1996).
Twen ty seven (60.0%) stud ies had in form a-tion about exp osu re to sp ecific agen ts, bu t on ly f i ve (11.1%) we re based on en viron m ental m e a-s u re m e n t a-s. Moa-st a-stu diea-s ua-sed job titlea-s (62.2%) an d/ or in du stries (46.6%) as th e m easure of th e e x p o s u re. Twen ty two stud ies (48.9%) got in for-m a tion fro for-m q u e stion n a ir es an d five (11.1%) u sed ch em istr y or in d u str ial hygie n e exp er t ju dgm en ts to com p lete th e ava ilab le in form a-tio n . This la tter p ro c e d u re h a s b een gen era l l y re c o g n i zed as th e re f e ren ce m et h od fo r exp o-s u re evaluatio n , a t leao-st for p op u latio n -b ao-sed c a s e - c o n t rol st u d ie s (Bo u yer & Hé m on , 1993; Stü cker et al., 1993).
In 34 stu d ie s of a to ta l o f 41 (82.9%), 68 n on -sta tistic ally sign ifican t association s we re fou n d . Two stu dies p u b lish ed on ly statistically sign ifican t a ssociation s. No assoc iatio n s we re seen in 29 of 39 stu d ies (74.3%) which re f e r re d to n egative re s u l t s. It is im p ossib le to en u m er-ate all of them , becau se som e of th ese associa-tion s we re n ot p oin ted ou t by th e auth ors.
Fifty fou r st at istically sign ifican t assoc ia tion s b etween solven t exp osu re or relat ed oc -c up at ion s or in d u st rie s we re re p o r ted in 25 stu d ies (55.5%). For each stu d y, th ese associa-tion s we re seen : (1) lym p h osarcom a an d p rox-im ity with ch em ical in d u str y; (2) b en zen e an d
re lat ed oc cu p atio n s; (3) p rin t in g; (4) st yre n e, t ri c h l o ro e t h y l e n e, p erc h l o ro e t h y l e n e, ben ze n e, oth er solven ts an d solven ts p lus chloro p h e n o l s a n d p h e n oxi a cid s; (5) solven t s (fe m a le); (6) wo od in d u str y; (7) lacq u er s an d va r n ish , en -gin e exhau st, h yd rocarbon coats an d clean ers, p ain t aerosols an d gasolin e as a clean in g agen t; (8) glu e s; (9) r u b b e r, p lastics an d syn t h e tic s; (10) solven ts; (11) et ha n ol u n it, for em en a n d i n s t r um en t m en ; (12) solven ts an d carp en ters; (13) m in eral oil; (14) car p er hou seh old an d car p er th ousan d s; (15) carp en ters an d oth er sim i-l a r; (16) car p en ters; (17) h igh exp osu re to soi-l- sol-ven t s a n d d iffu se N HL; (18) sh oe wo rk e r s, p o rcelain work e r s, fu r n i t u re workers an d lorry d ri ver s; (19) organ ic solven t s; (20) ch em ical w o r ke rs less t h a n 65 yea r s; (21) styre n e less than 10 years of exp osu re with 1-49% o f work-e rs in p rod u ct io n swork-ec tion ; (22) m work-ec h an ics, e l e c t ron ic an d electrical repairs an d sh ip b uild-in g; (23) m ixtu re of b e n ze n e, t olu en e a n d xy-len e a n d in ks; (24) b en zen e; (25) solven ts an d sm all cell d iffu se.
In a review of the epidem iology of the occup at io n al fac to rs o f ch e m ically in d u c ed lym -p h oid an d hem o-p oietic can cers, the d ifficulties a sso cia ted with su ch a re view a re re c o g n i ze d . Th ey are m ain ly related to b oth disease an d exp o s u re d efin ition s. Howe ve r, c on sist en t fin d in gs we re re p o r ted for occ u p ation s with b en -zen e exposu re (Ts o n g a s, 1985). An oth er re v i e w a b o ut le u kem ia an d lym p h om a r isks d eri ve d f ro m solve n ts p o in te d ou t th at a r elat ion b et ween solven et exp osu re a n d m a lign a n et lym -p hom as has b een called in to qu estion (Bra n d t , 1987). The author re f e r red th e con tra d i c t o ry re-su lts from sp ecific stud ies an d m en tion ed that th e reason s are obscure. It was exp lain ed that, a p p a re n t l y, the stu dies wh ich failed to fin d an a ssociation we re b ased on register d ata o r occ up at ion a l t itles, su gge stin g th e n ee d for fu r -th er in vestigation s in -th is field.
So m e o ccu p ation s we re sh own to b e re l a te d with N HL as in th te c astes of th te r u b b te r in -d u s t r y (Mo n son & Na k a n o, 1976; Wilc osky et a l., 1984; De l zel & Mo n so n , 1984); p et ro l e u m
re fin in g wo rkers (Th om as et a l., 1982; Wen e t
a l., 1983; De l zell et al., 1988); chem ists (Li et al.,
1969; Sea rle et al., 1978; Olin , 1978; Olin & Ah lb om , 1980; Rin sky et a l., 1988); p r i n t e r s ( Zolot h et a l., 1986); high wa y worke r s (Ma
i-zlish et al., 1988); dry clean ers (Blair et al., 1 9 9 0 )
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Be yon d th e m illion s of in d u strial work e r s with p oten tial exp osu re to solve n t s, the gen era l p op ulation is also p oten tially exp osed thro u g h c on tact with com m ercial p rod ucts an d co n ta-m in a te d d rin kin g wat er. Bec au se e xp osu re s h a ve in c rea sed over t h e sa m e t im e p er iod a s t h e in c rea se in NHL, it is p lau sib le th a t sol-ven ts m ay h ave con tr ibuted to risin g in cid en ce (Ries e t al.,1994). Be s i d e s, a low r isk was o b -s e r ved for all lym p h o-h em a top o ietic c an cer-s, in clu d in g NHL in Circu m p olar In u it, wh ic h sugge st ed th at it m a y re flec t p ro t e c t i ve en vi-ron m en t or gen et ic fact ors (La n ier & Alb ert s, 1 9 9 6 ) .
Twen ty three stud ies (51.1%) con clud ed ei-th er ei-th at ei-there was n o association , or ei-th at ei-th ere was n o n ee d fo r fu t u re in ve s t i g a t i o n s, even if t h e re was th e p ossib ility of re l a t i o n s h i p. So m e stu dies su ggested that organ ic solven ts can act as a r isk fa ct or for NH L d evelop m en t. It wa s n oticed in th is review t h a t statist ical sign ifi-can c e wa s m ore fre q u en t ly sh own in st u d ies w h e re solven t exp o su re wa s m o re ac cu ra t e l y defin ed , OR = 5.2 (1.11-26.19) – exposu re to or-gan ics solven ts was sp ecifically evalu ated : ye s / n o ; results with sta tistica lly sign ifican ce: ye s / n o. Eigh teen su ch stud ies, 13 (72.2%) d efin ed or su ggested or gan ic solven ts as p o ssib le ri s k factors for NHL.
Ta b l e 1
Stud ie s o n no n-Ho dg kin’s lymp ho ma in relatio n to p o te ntial o c c up atio nal o rg anic so lvents e xp o sure .
A u t h o r s / y e a r / D e s i g n S o u rce population St udy Disease E x p o s u re Result s c o u n t ry S u b j e c t s C l a s s i f i c a t i o n
1- Cap urro , 1979, Clinical A c o mmunity o f C aucasian 117 ind ivid uals Ly m p h o m a So lve nt e xp o sure 23 c ases o f canc er, 8 o f U S A c ase serie s peo p le fro m 1968 to 1974 m e a s u red in the the m were lymp ho ma;
e n v i ro nment and in c o nside ring spe cific ally the blo o d o f the re s i d e n t s the 3 deaths due to
l y m p h o s a rco ma in a 6 ye ar p erio d, O / Ei= 3/0 .0187= 160 fo ld
2- Vianna & Po lan, C o h o rt All deaths male ≥ ag e 20 1 46 RCS; 353 RCS; LS Benzene – RCS: RRi i i= 1.6; 1979, USA m o rt a l i t y with RCS, LS o r HDi if ro m LS and 267 HD and HD related o cc upatio ns LS: RR = 2.1;
de ath ce rtific ates o f Ne w HD: RR = 1.6
Yo rk State , e xc luding Ne w Fo r 45 ye ars o ld and o ver: Yo rk City, fro m 1950 to 1969 RCS: O / E = 1.7 p< 0.01
LS: O / E = 2.1 p < 0.01 HD: O / E = 1.9 p < 0.01
3- Canto r & E c o l o g i c a l Ag e ad justed mo rtality 3 ,056 c o untie s I C Di v200, P ro p o rtio n o f p rinting , Asso c iatio ns in a multiple
Fraume ni, 1980, USA rate s fo r NHLi iin co untie s 202 and 205 c he mic al, petro l e u m , re g re ssio n analysis fo r o f the co ntig uo us U.S. f u rn i t u re , e lec trical, white male s and p rinting
m a c h i n e ry and rubb er (βsig nific ant at p < 0.025), industrie s p er e ac h c o unty p e t ro c he mic als and
rub ber p ro d ucts
4- Hard e ll e t al., H o s p i t a l - Case s: all men assiste d in Cases: 109 Luke s-Co llins Se lf administe re d lo w g rade: RR = 1.2 1981, Swe de n based c ase - the Dep. O f O nc o lo g y in NHL and ( m o d i f i e d ) q u e s t i o n n a i re s, (0.5-2.6); hig h grad e
c o n t ro l Ume a (c atchment area), 60 HD; sup ple mente d b y ( S t y rene, tric hlo ro e t h y l e n e , 25-85 ye ars o ld ; c o ntro l s : c o n t ro ls: 338 telepho ne ; hig h and lo w p e rc h l o ro e thyle ne , 8 matc he d (ag e, sex, g rad e so lve nt e xp o sure b enzene): RR = 4.6 re sid ence ) co ntro ls fo r eac h (1.9-11.4), o the r: RR = 2.8 living case and 10 matc hed (1.6-4.8); hig h + lo w: (ag e, sex, resid ence and ye ar RR = 2.4 (1.5-3.8); o f de ath) fro m the Natio nal so lvents + chlo ro p h e n o l s
Po p ulatio n Reg istry and p he no xy ac id s:
RR = 8.5 (4.4-17.2)
5- Me inhard t e t al., C o h o rt Wo rkers in 2 styre n e - Plant A: H e m a t o p o i - Butadiene, styre n e Lymp hatic and 1982, USA m o rt a l i t y butadiene rubb e r p lants 1 662 ind iv. e tic and and be nze ne he mato p o ietic tissues
3 4,187 p / y lymp hatic e n v i ro nme ntal (220-205): SMRi i i= 1 5 5 Plant B: malig nanc ie s m e a s u re s (p lant A) and 78 (p lant B); 1094 indiv. ICD: 200-205 lympho and re t i c u l o s a r-1 9,742 p / y c o ma (200): SMR= 181
Cad. Saúde Púb lic a, Rio d e Jane iro , 14(Sup . 3):41-66, 1998
Tab le 1 (c o nt.)
A u t h o r s / y e a r / D e s i g n S o u rce populat ion St udy Disease E x p o s u re Results c o u n t ry S u b j e c t s C l a s s i f i c a t i o n
6- Balarajan, R e g i s t ry - C ase s: malig nant Case s: 426 ICD 8t h: Ro ad transp o rt wo rke rs ICD 200: d rive rs o f b uses 1983, UK based c ase lympho mas in men l y m p h o m a s 200 and and c o aches: O Riii = 1.16
c o n t ro l ag ed 15 and o ve r, fro m (256 NHL); 2 0 2 (0.60-2.26); d rivers o f o the r 1973 to 1977 co lle cted c o n t ro ls: 256 ro ad p asse ng e r vehic les: at the Natio nal Cance r O R = 0.95 (0.48-1.88); R e g i s t ry; co ntro ls: rando mly d rive rs o f ro ad g o o d s c ho sen fro m o ther c ance rs, ve hic le s: O R = 0.93 (0.71 matched 1:1 by age , se x and 1.22); bus c o nducto rs: re g io n o f re s i d e n c e O R = 0.57 (0.12-2.25);
l o rry d rive rs’ mates, etc.: no cases; IC D 202: drive rs o f b use s and c o aches: O R = 1.63 (0.62-4.52); d rive rs o f o ther ro ad p asse ng er vehic les: O R = 1.67 (0.68-4.32); d rive rs o f ro ad g o o ds ve hic le s: O R = 0.90 (0.63-1.28); b us c o nd ucto rs: O R= 2.67 (0.64-15.6); lo rry d rivers’ mate s, e tc .: no cases
7- Franc o & H o s p i t a l - Cases: patie nts o f bo th Cases: 282 N H L O c cup atio ns as p ro p o se d Chemical and Po nte, 1983, b a s e d sexes ad mitted to the NHL and 387 b y the Annuario p h a rmace utic al: 4 ECi i i, I t a l y c a s e - c o n t ro l C linica Me dica A. Ferrata - HD (347 male Statistico Italiano O R = 0.16; Textile s, sho es
University o f Pavia, fro m and 322 and le athe r: 21 EC, 1969 to 1980, d iag no se d fe male; O R = 0.50; Paper and as malig nant lympho ma; c o n t ro ls: 7 57 p rinting : 3EC, O R = 0.90; c o n t ro ls: patie nts male and 588 rubb er and plastics: 3 EC, ad mitted to an inte rn a l f e m a l e O R = 0.33; wo o d : 14EC,
medic ine unit in Pavia O R = 5.55 (2.39-12.85)
f ro m 1975 to 19 80
8- Bern a rd et al., H o s p i t a l - Case s: all ne w cases Cases: 81 male N H L Q u e s t i o n n a i res app lied O cc upatio nal so lvents 1984, UK based d iag no sed b e twe en and 77 fe male b y o ne interv i e w e r ; (e xc lud ing be nze ne):
c a s e - c o n t ro l O c to b er/ 1979 and NHL; 48 HD; p ast o c cup atio ns O R = 1.52 (0.70-3.26) De ce mbe r/ 1981 in ad ult 66 CLLi i; 13 ALL and selec te d exp o sure s male; O R = 7.71 (1.24-reside nts in six health c o n t ro ls: 162 male 47.93) fe male; pe tro l e u m d istric ts in Yo r k s h i re and 154 female industries: O R = 4.21 Health Reg io n; co ntro ls: p atie nts fo r NHL (0.54-32.79) male ; 1:1 ho sp ital p atients, c a s e s so lvent use as ho b by: matc he d fo r ag e , se x and O R = 1.39 (0.30-6.46) g e o g rap hic are a male ; b e nze ne: O R = 0.49
(0.21-2.0) male; p e tro l p ro d uc ts: O R = 0.59 (0.25-1.39) b o th se x; hair sp rays: OR = 1.49 (0.75-2.95) female; hair sprays: O R = 4.67 (1.50-13.63) fe male > 65 ye ars o ld
9- Gile s et al., P o p u l a t i o n - Cases: all incident Case s: 798 All c ase s Perso nal inte rv i e w ; Male fo undry wo rkers: 1984, Australia based c ase - cases o f to tal c ase s, revie we d by o c c u p a t i o n s O R = 8.0 (1.07-356.0);
c o n t ro l m y e l o p ro liferative 241 NHL (125 an o nco lo g ist, fe male haird re s s e r s : and lympho pro liferative male and 116 a hemato lo g ist 5 expo sed cases and no d iseases in Tasmania female); and a patho lo g ist exp o se d co ntro l s f ro m 1972 to 19 80; c o n t ro ls: 241
