8 7
Cad. Saúde Púb lic a, Rio d e Jane iro , 14(Sup. 3):87-98, 1998 A RTIGO A RT I C L E
O n t he need t o assess cancer risk
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1 De p a rtm en t of Bi o s t a t i s t i c s a n d Ep i d e m i o l o gy, Tu l a n e Un i v ersi t y Gra d u a te Sch o ol. 150 1 Can a l St re e t ,
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Ru a Co elh o e Ca s t ro 6, S a ú d e , Rio d e Ja n e i ro, R J 2 0 0 8 1 - 0 6 0 , Bra z i l . g u i t a t i @ r i o. n u t e c . c o m . b r
Gu i lh erm e Fra n co N et t o 1 , 2
Abstract Ev id en ce ex ist s t h at ex p o s u re t o p ou lt ry on cogen ic v iru ses m ay p rod u ce elev at ed ca n cer m ort a lit y in h u m a n p op u lat i on s, p a rt i c u l a rly ex cesses o f ca n cer of lu n g a n d ex cesses of ca n -cer of lym p h op oiet ic t issu es. To d a t e, t h i s p ot en t ial risk is u n k n ow n in p op u la t io n s from t h e d ev elop in g cou n t ries. Th i s p a p er su ggest s t h e n eed t o a ssess ca n cer risk in p o p u la t ion s of d eeve l o p -in g cou n t ries w it h re p o rt ed en v iron m en t a l ex p o s u re t o ch ick en m eat p rod u ct s a n d eggs; t h e n eed t o a ssess risk of ca n cer in p op u la t ion s in ocu la t ed w it h v a ccin es from i n fect ed ch ick en em b ry o s ; a n d t h e n eed t o a ssess risk of ca n cer in occu p a t ion a l p o p u la t ion s h igh ly ex p osed t o p ou lt ry on co-gen ic v iru ses, a n d w it h p ot en t ia l con cu rren t ex p o s u re t o ch em i ca l aco-gen t s k n ow n or su sp ect ed t o be carc i n o g e n s .
Key words Ep i d e m i o l o gy ; Po u l t ry ; On cogen ic Vi r u s e s ; Be n ze n e ; Ca n c e r ; Mo rt a l i t y
Resumo Ex ist e ev i dên cia d e qu e ex p osiçã o a v íru s on cogên i cos d e a v es p ossa p rodu z ir eleva d a m o rt a lid ad e d e câ n cer em p op u lações h u m an a s, h a v en d o p a rt icu la rm en t e ex cesso d e câ n cer d e p u lm ã o e d os si st em a s li n fá t i cos e h em op o iét icos. At é o m o m en t o, esse ri sco p ot en cia l é d esco-n h ecid o em p op u la ções d os p aíses em d eseesco-n vo l v i m e esco-n t o. Est e m a esco-n u scrit o su gere a esco-n ecessid a d e de a v a lia r o risco d e cân cer em p op u la ções d os p a íses em desen v olvi m en t o com sa b ida ex p osiçã o a p rod u t o s a v íco la s e ovo s ; a n e cessid a d e d e a v a li a r o ri sco d e câ n ce r em p o p u la ções qu e f ora m i n ocu la d a s com v a ci n a s d esen v o lv i d a s em em b riõ es d e a v es co n t a m i n a d a s e a n ecessi d a d e d e a v a lia r o ri sco d e câ n cer e m p o p u la çõ es d e t ra b a l h a d o res co m gra n d e ex p osiçã o a v í ru s on co -gên ico d e a v e s , e co m p ot en cia l ex p osi çã o si m u lt â n ea a a gen t es qu ím i co s qu e são re c o n h e c i d o s ou su sp eit os carc i n ó g e n o s .
Cad . Saúd e Púb lic a, Rio de Jane iro , 14(Sup. 3):87-98, 1998 I n t ro d u c t i o n
Se ve ra l vir u se s a re kn own ca rcin oge n s fo r h u -m a n s. Exa-m p les are th e re t rov i ru s H TLV, wh ich p r o d u ce s Tc e ll le u ke m ia; H e p a t it is B He p t a v i ri n i d a e , wh ich is re la t e d wit h h e p at o ce llu -la r c ar cin om a ; Ep s t e i n - Ba rr He r p e s v i rid a e is a ss o cia t e d wit h Bu rk i t t ’s lym p h o m a a n d n a s o p h a r in ge a l carcin om a s; a n d H PV Sh o p e p a -p i l l o m a v i ru s.
Th e Avia n Le u ko s is a n d Sa rc o m a Vi ru s ( A L S V), t h e Re ticu lo e n d oth e lio sis Vi r u s (REV) , a n d Ma re k’s Disea se Vi r u s (MDV), cla ssified a s t h e Po u l t r y On co ge n ic Vi r u se s gro u p , a re we l l d ocu m e n ted as ca n cer ca u sin g agen t s in ch ick-e n . Th ick-e y p ro d u cick-e a cu t ick-e o r ch r o n ic t u m o rs o f t h e He m a t o p o i e t i c / Lym p h a t ic Syst em s (H LS), e n d o t h e l i o m a s, fib ro s a rc o m a s , ca n c e r o f t h e k i d n e y, visce r a l lym p h o m a s a n d n e u r o l y m p h o m a t o sis a m o n g s e ve ra l b ird sp e c ie s (Sve t -Mo l d a v s k y, 1957; Ah lst ro m , 1964; Ha r r is & C h e s t e r m a n , 1964; Alt a n e r & Sve c , 1966; Si m k ovic, 1964; Pu rch a se & Wi t t e r, 1986).
Th e p re va le n ce o f t h e se in fe ct io n s is c o m -m o n a-m o n g c h icke n a n d b ird s wo rld wid e . Th e s e viru s e s s h o w p o t e n t ia l fo r su rvivin g in t h e e n viro n m e n t . H u m a n e xp o s u re t o t h e s e v i ru ses o ccu rs ve ry oft en th ro u gh ge n era l p op -u la t io n co n t a c t wit h , an d c on s-u m p t io n o f c h i c k e n / t u rke y m e a t p ro d u ct s an d e ggs, e xp o s u r e o f t h e ge n e ra l p o p u lat io n fr o m in oc u la -t io n w i-t h va c cin e s p re p a re d fro m in fe c-t e d ch icken e m b ryo s, or m o re in t en sely, by co n ta ct d u rin g o ccu p at ion al e xp o su re.
Mo st o f t h e e xis t in g e p id e m io lo gic d a t a , b ased o n fa rm e r s, ve t e ri n a ri a n s, an d r u ral p o p -u la tion s fro m th e USA a n d E-u ro p e, h ave show n a sso cia t ion s b et we en h u m an can ce rs, p a rt i c u -la rly o f t h e lym p h o p o iet ic syst e m s, an d b r o a d s u r ro ga t es for e xp o su re t o t h e se viru s e s. How-e vHow-e r, in a d How-e q u a tHow-e d How-e sign a n d / o r n on -co n t ro l of p o ten t ia l con fo un d in g to ot h e r kn own ca rc i n o -ge n ic a -gen ts such a s p e sticid e s, fe rt i l i ze r s, a n d r a d ia t io n , m ake it d ifficu lt to in t e rp re t t h e s e f i n d i n g s.
Mo re re c e n t l y, a n a lyt ic e p id e m iolo gic in -vest iga t io n s b a se d on coh o rt s o f wo r ker s fr o m s e ve ra l job -ca te go ries fro m th e US m e at in d u s-t r y h a ve co n s is s-t e n s-t ly re p o r s-t e d e xce ss risk o f d e at h fro m m u lt ip le m ye lo m a, le u ke m ia , Ho d g k i n’s Di s e a s e, n o n - Ho d g k i n’s lym p h o m a , lu n g ca n ce r, a n d t o a le sse r e xt e n t , o t h e r can -c e r s.
Re ce n t lab o ra t o ry d at a h as p rovid e d d e fin i-t i ve se ro lo gical evid e n ce of h u m an in fe ci-tion o f A S LV a n d REV ( Jo h n so n , Nich o ls o n & Du ra c k , 1995; Jo h n so n , Ove r by & Ph ilp o t , 1995; Ch o u -d a t et al., 1996). Th ese fin -d in gs co m b in e -d wit h
t h e e xist in g e p id e m io lo gic d a t a su gge s t t h at Po u l t r y On co ge n ic Vi ru se s a re p o te n t ia lly ca n -cin oge n ic for h u m a n s.
Co n co m it a n tly wit h refin e d viro lo gica l a n d m o le cu la r st u d ie s, t h ere is t he n eed t o con d u ct so u n d e p id e m io lo gic in ve stiga t ion s in gro u p s of su b ject s wit h we ll ch a ra c t e ri ze d exp osu re to th ese viru s e s, as ch icken p ro c e s s i n g / s l a u g h t e r-in g p la n t wo rk e r s, r-in o rd e r t o yie ld d e fr-in it ive co n clu s io n s wh e t h e r t h e in fe c t ivit y a n d t h e on co ge n icit y o f Po u l t r y On cogen ic Vi ru se s re p -re sen t a p u b lic h e alth th -re a t .
Be sid e s t h e vira l h yp o th e sis , ca n c e r in t h e m ea t in d u st ry m ay also b e rela t e d t o so m e o c-cu p at io n a l ch e m ica l e xp osu re s. Resu lt s from a m o rtalit y coh o rt co n d u ct ed in th e m e a t in d u s-t r y, in clu d in g a s u b -c o h o r s-t o f wo rke rs in s-t h e m e a t d e p a r t m e n t fro m gro c e r y st o re s / s u p e r-m a rk e t s, su gge st in g t h a t e xp o su re t o fu r-m e s e m itt e d fro m t h e t h e r m a l d e co m p os it io n o f p o lyvin yl c h lo rid e (PVC) d u r in g wr a p p in g o f m e at m a y a ls o p la y a ro le in t h e e xce ss e s o f lu n g c a n c e r a n d c a n ce rs o f t h e H LS in t h e se w o rk e r s. Fu m e s fro m PVC c o n t a in c h e m ica ls k n own t o b e h u m a n ca rcin o ge n s su ch as b e n -ze n e an d Po l yciclic Aro m a t ic Hyd ro ca r b o n s – PAH s (Sn yd e r e t al., 1993; Aksoy, 1989; Bre t t e t a l., 1989; Ha m m o n d e t a l., 1976; Ll oyd , 1971; Ma c l u re & Ma c Mah o n , 1980; Ma zu m d a r e t a l., 1975; Re d m o n d e t a l., 1976), a n d p h t h a lat e s wh ich p ro d u c e c an ce r in a n im a ls. Wra p p i n g a n d la b elin g act ivit ie s in t h is in d u str y a re p re -d o m in a n tly ca rr ie-d o u t by wo m e n .
To d a t e, t h e e p id e m io lo gic in ve s t i g a t i o n s on t h e role o f p o u lt r y on coge n ic viru se s in h u -m a n ca n ce r d o n o t in c lu d e p o p u la tio n s fr o -m d e velop in g co u n t ri e s.
Th e o b jective of th is p ap e r is t o ad d ress t he n e ed t o co n d u ct ca n ce r risk a sse ssm en t in h u -m an pop u lation s p oten tially exp osed to p ou ltry on coge n ic viru ses in e n viro n m e n t a l a n d o ccu -pation al p opu lation s from d evelopin g cou n tri e s.
General population exposure
l-Cad . Saúde Púb lic a, Rio de Jane iro , 14(Sup. 3):87-98, 1998 i f o rn ia , U SA (Fasa l et a l., 1968). Th e a ut h o rs re
-p o rt ed a h ighe r risk of m o rtality fro m leu kem ia a m o n g b ot h m a le a n d fe m a le fa r m re s i d e n t s wh e n co m p ared wit h t h e st a te ge n era l p op u la t io n . Th e in ve s t iga t o rs su gge st e d t h a t a c om -m on fa ct or to t h e fa r-m e n viro n -m e n t co uld b e a p ossib le exp la n a t io n to t h e fin d in gs.
Se ve ra l le u ke m ia clu st e rs re p o r t e d sin c e 1905 we re re v i e we d (Ale ksa n d ro w i c k s, 1968). Alth ou gh th e au th or correlates h u m an leu kem ia wit h ca t t le le u ke m ia, re f e re n ce w a s m a d e t o th e ro le of Ro u s ch icken t u m ors a s a risk fa ct or. A c a se -co n t ro l st u d y wa s c on d u ct e d b a se d o n t u m o r re g i s t r y d a t a in t h e st a t e s o f Ne w Yo rk, Ma r ylan d , an d Min n eso t a , U SA (Bross e t a l., 1972). Th e risk o f d yin g fro m le u kem ia a ft er h a vin g b e e n e xp o s e d t o c h icke n s a ga in st t h e risk o f n o t b e in g e xp o se d t o ch icke n s was s t a -t is-t ica lly sign ifican -t . Ta kin g in -t o co n sid era -t i o n t h e h e a lt h s t a t u s o f t h e a n im a l, h u m a n s e xp o se d t o sic k a n im a ls s h owe d s t ro n ge r a ss o -c ia t io n with -c a n -c e r, e s p e -cia lly in t h e a -cu t e le u ke m ia ser i e s.
An e c o lo gica l st u d y w a s co n d u ct e d o n t h e p o u l t ry p o pu latio n by cou n t y fo r 10 so u t he a st -e rn s t a t -e s in t h -e U SA, d -e ri v-e d fro m t h -e 1964 Ce n su s of Agri c u l t u re (Pie st er & Ma son , 1974). Th e h u m a n m o r t alit y ra t e d u e t o c a n ce r, b y c o u n t y, d u rin g t h e p e rio d 195069 w a s d e t e r -m in e d fro -m in fo r-m a t ion p ro vid e d b y t h e U S Na t ion a l Ce n t e r fo r H e a lt h St a t i s t i c s. In t h e cou n t ies of h igh d en sity o f p o u ltry p op u la t io n , a sign ifican t, co n siste n t asso cia tio n , ta kin g in -to co n sid e ration all fo ur p o ssib le com b in a tion s b e t w e e n ra ce (wh it e an d b la ck) a n d se x (m a le a n d fe m a le), was o b serve d fo r m ye lom a . Ut e r-in e a n d ova ria n cervica l can cers we re e xc e s s i ve in h igh po u lt ry p o pu la t io n are a s, b u t t h e e ffe ct d i s a p p e a red wh en d at a was co m pa re d wit h th e to t a l U S p op u la t ion .
Th e in cid e n t ra t e s o f le u ke m ia in Ol m s t e d Co u n t y, Min n e s ot a , U SA, d u rin g t h e d e ca d e 1965-1974 w e re in ve st iga t e d (Lin o s e t a l., 1978). Th e in cid en t rat e was sign ifica n t ly h igh -er a m o n g m a les t h a n a m on g fem ales, espe cia l-ly in t h e o ld e r a ge gr o u p s. Ru ra l ra t e s we re g re a t er t h a n th e u r b a n o n e s. T h e rap e u t ic ra d i-at io n e xp o s u re wa s n o t t a ke n in t o a cco u n t . Pe s t icid e s e xp o su r e a s w e ll a s a n im a l b or n e v i ru s we re p o t en tia l exp o su re s d iscu ssed .
A clu st e r o f s e ve n ca se s o f p r i m a r y b ra i n n e o p la sm in a sm a ll t own wa s re p o r t e d in t h e St a t e o f Mi s s o u r i, U SA (Mo ra n t z e t a l., 1985). Ex p o s u re e ith e r to a sh o e fa cto r y o r to a ch icken h a t ch er y we re re p o rt e d b y p at iicken ts o r n e xt -o f-kin . Six -o f t h e t u m -o r s w e re d ia gn -o se d as glio b la stom a m u ltifo r m . No con t ro ls we re u t i-l i ze d . Ca ses we re a ct ivei-ly se a rch e d in t h e t ow n
CANCER RISK IN DEVELO PING CO UNTRIES 8 9
b u t n ot in th e co m p a rison grou p s wh ich m igh t b ia s th e e st im at e.
A h igh in c id e n c e o f n o n Ho d g k i n’s lym -p h om a ove r a ge 21 wa s re -p o rt ed in ea ster n Ne-b r as ka , U SA (We i s s e n Ne-b u rge r e t a l., 1986). T h e d isease wa s stu d ied in relatio n to corn p ro d u c-t io n , c-t o c-t a l p e sc-t icid e s, h e rb icid e s, a n d in se c c-t i-c id e s i-co u n t y a gr i i-c u l t u ra l i-c h ar a i-c t e ri s t i i-c s. T h e fin d in gs su gge s t e d t h a t t h e in cr e a se d in ci-d e n ce o f n o n -Ho ci-d g k i n’s lym p h om a m a y b e re-lat e d to in t en se agr i c u l t u ral a ct ivity.
Re p o r t s o n h igh ra t e s for n o n - Ho d g k i n’s lym p h om a a n d Ho d g k i n’s Disea se am on g w h i t e m a le re sid e n t s o f Han co ck Co u n t y, Oh i o, U SA, d u r in g 1960-1979 we re a s s e ss e d b y m e a n s o f a c a se - co n t ro l s t u d y (D u b row e t al., 1988). Ca use o f d e a th a n d u su a l occu p a t io n we re a b -s t ra cte d fro m t h e d eat h cert i f i c a t e -s. Th e m a jo r fin d in g o f t h e s tu d y sh ow s t h a t n o n -Ho d g k i n’s lym p h om a wa s asso cia t e d wit h t h e fa rm e r o c-cu p a tio n a l gro u p .
A ca se -con t ro l stu d y was con d u ct ed in Swed e n (Pe rs o n e t al., 1989). Oc cu p a t io n a l e xp o -s u re-s to -so lve n t -s, p he n oxy acid -s, cre o -s o t e, work a s a ca r p e n t e r, a n d co n t a ct wit h p e t s (o t h e r th an d ogs, cat s, an d b ird s) we re asso ciate d wit h s ign ifica n t ly in cre a s e d risk fo r n on -Ho d g k i n’s lym p h o m a. Occu p ation a l exp o su re to so lve n t s, we ld in g, w o o d p re s e r va t i ve s , p h e n oxy a cid s , a n d fre sh wo o d p re se n t e d sign ific an t ris k fa c-t o rs fo r Ho d g k i n’s Di s e a s e .
A p o p ulat ion - b a sed ca se-con t rol stu d y was c o n d u ct e d in a n a re a wit h a h igh in cid e n ce o f m u lt ip le m ye lom a with th e p u rp o se to id en t ify a n d e valua te su sp ec te d e n viro n m e n tal fa c to rs ( Er ickso n & Ka rlso n , 1992). Pre vio u s a sso c ia-t ion s b eia-t we e n fa rm in g a n d m u lia-t ip le m ye l o m a we re c o n firm e d . Dom e s t ic a n im a ls a n d p e st i-cid e s we re p o sitive in d ica t or s.
F a rming occupation re p o rt s
A ca se - co n t ro l st u d y wa s c o n d u ct e d in t h e St at e s o f Wa sh in gt o n a n d O re go n , U SA, u s in g d e at h ce rt ificat es (Milh an , 1971). A sign ifica n t a sso ciat io n was fo u n d b e tw e en fa rm in g o ccu -p a tion s an d d ea t h from le u ke m ia a n d m u lti-p le m yelom a. Th e a sso ciatio n w as st ron ger in m en u n d e r age 60 wit h lym p h at ic a n d a cu te typ es o f le u ke m ia . Po u l t r y fa rm e rs sh owe d t h e h igh e st p ro p o rtio n case e xcess in th e leu ke m ia se ri e s.
Cad . Saúd e Púb lic a, Rio de Jane iro , 14(Sup. 3):87-98, 1998
b e f o re age 66. Sign ifica n t ly e le va t e d risk fo r f a r m e rs fro m h e a vy co rn p ro d u cin g c o u n t ie s wa s fo u n d . Wh e n st r a t ifie d b y t h e ch ic ke n in -ve n t o ry, t h e d a t a p re s e n te d a n o n -s ign ifica n t e xc e s s ris k o f le u ke m ia : Od d s Ra t io o f 1.23 (95% CI 0.961.58) for t h e h igh est ch icke n d en -sit y co u n t ie s a n d Od d s Ra t io o f 1.27 (95% C I 1.00-1.62) fo r t h e o t h e r c h icke n p o p u la t io n co u n t ie s (low a n d in te rm e d ia te ch icken d en si-t y). Th e u s e o f o cc u p a si-t io n a l d a si-t a d ra wn fr o m d e a t h ce r t ific a t e s is a we ll kn own p o t e n t ia l s o u rc e o f b ias. Th e a u t h o r s d isc u s se d t h e p o -t en -tial e xp o su re fro m ca rcin oge n ic su b s-t a n ce s su c h a s s o lve n t s, o ils, fu e ls, we ld in g fu m e s , h e r b i c i d e s , in se ct icid e s, a n d o rga n ic d u st , a s well as a n im a l leu ke m ic viru s.
Age - a d ju s t e d m o r t a lit y ra t e s fr o m 1971 t o 1978 fo r wh it e m a le fa rm e rs a n d n o n -fa rm e r s we re c o m p u t e d fr o m d e a t h ce rt ifica t e s in Iowa , U SA (Bu rm e i s t e r, 1981). A p ro p o rt i o n a t e m o r talit y a n a lysis wa s d on e for t h e m ajo r can -c e r sit e s wh i-ch p re s e n t e d h igh e r -ca n -ce r r i s k a m o n g fa rm e rs fo r lip , st o m a c h , le u ke m ia , lym p h a t ic, m u ltip le m ye lo m a, a n d p ro s t a t e.
A c a se -c o n t r ol s tu d y m a t c h e d b y co u n t y, a ge a t d e a th , a n d ca le n d ar yea r was co n d u ct ed in Iowa , U SA (Bu rm e is t e r e t a l., 1982). W h i t e -m ale le u ke -m ia d e at h ce rt ifica t es fo r th ose ove r age 30 wh o d ie d b e tw ee n 196478 we re in clu d -e d in t h -e st u d y. Th -e ov-e ra ll O d d s Ra t io for f a rm in g an d leu ke m ia wa s fou n d t o b e st a tist i-ca lly sign ifii-ca n t. By t h e u se o f str a tifie d a n a ly-s i ly-s, t h e a u th o rly-s re p o rt e d a ly-st a t ily-st ically ly-sign ifi-c an t a sso ifi-cia t io n b e t we e n le u ke m ia a n d a ifi-cre s t re a t e d wit h h e rb icid e s an d e gg-la yin g ch ick-e n s p ick-e r co u n t y. Ch ro n ic lym p h at ic lick-e u kick-e m ia p o s i t i ve fin d in gs we re m o re co n sist e n t t h an u n sp ecified lym p h at ic le u ke m ia.
An o t h e r e p id e m io lo gic in ve s t iga t io n wa s c o n d u c t e d t o o b se r ve if so m e o t h e r t yp e s o f ca n ce r w o u ld p re s e n t t h e s a m e p a t t e rn a s le u ke m ia d id in t h e p re vio u s e p id e m io lo gica l i n ve st igat io n s co n d u c t e d in t h e st a t e s o f Ne -b ra ska a n d Iowa , USA (Bu rm e ist er et al., 1983). Th e aim o f t h e st u d y wa s to id e n t ify wh e t h e r n o n - Ho d g k i n’s lym p h o m a, m u ltip le m ye l o m a , st om a ch can cer, a n d p ro st a te can cer m o rt a l i t y we re as so cia t e d wit h s o m e fa rm in g p ra c t i c e s , p a r t icu la r ly in se c t icid e e xp o su re. Wh it e m ale Iowa re sid e n ts who d ie d of t h ose d ise ases fro m 1964- 78 we re in clu d e d in t h e st u d y. Am o n g o t h e r fin d in gs, m u lt ip le m ye lo m a a n d n o n -Ho d g k i n’s d isea se p resen te d sta tistica l associa-t io n a m o n g associa-t h e c o u n associa-t ie s wiassocia-t h h igh e gg-la yin g c h ic ke n a c t ivit ie s. Th e a u t h o rs su gge st e d fu r-t h e r in ve sr-t igar-t io n o n r-t h e p o r-t e n r-t ia l ro le o f Ma re k’s d ise ase b e t a ke n in acco un t a s a p o ssi-b le e tio lo gic fa ct o r.
D a t a o n o ccu p a tio n a l a n d fa m ily h ist o r y we re co llected in a p op ulation -b ased in cid en ce c a s e - c o n t rol stu d y in Tasm a n ia, Au s t ralia , in or-der to assess m ye l o p ro l i f e ra t i ve an d lym p hop ro-l i f e ra t i ve d isord ers sp ecific ri s k s, an d to exp ro-lore p o ssib le co m m on et io lo gie s (Gile s et al., 1984). Am o n g farm e r s, a st a tistically sign ifican t Od d s Ra t io wa s fo u n d fo r t h e ove ra ll d ise a se -gro u p , b u t n o im p o r t a n t d iffe re n ce s we re fo u n d b e -t ween -th e sp ecific -typ e of d iagn osis a n d -th e -tim e o f em p loym e n t (e ve r o r m o re t h an five ye a r s ) . Vi ru s e s, ch e m ica ls, a n d io n izin g ra d ia t io n a re th e th re e b ro a d t yp e s o f en viro n m e n ta l a ge n t s th ou gh t t o b e e t iolo gica lly re la t e d wit h m ye l o -p l o ri f e ra t i ve an d lym -p h o-p ro l i f e ra t i ve d isord e r s. A ca s e - c on t ro l s t u d y a m o n g w h it e m a le re sid e n t s in t h e s ta t e o f Wisc on sin , U SA, wa s co n d u c t e d (Ca n t o r & Bl a i r, 1984). Th e aim s o f t h e in ve s t iga t io n we re t o t e st t h e h yp o t h e s is wh e t h e r fa r m e r s wo u ld h a ve e le va t e d risk o f m u lt ip le m ye lo m a, a n d if s o, t o in ve s t i g a t e w h ic h agr i c u l t u ral fac t o rs m igh t b e re la t e d t o t h e d is e a se . Th e cr u d e O d d s Ra t io s h o we d a sign ifica n t a s s oc ia t io n . Ta kin g in t o a c co u n t ye a r o f b irt h , t h e as s o cia t io n b e t we e n h igh ch ic ke n in ve n t o ry an d m u lt ip le m ye lo m a is sign ifica n t in t h e gr o u p b o r n b e t we e n 1897-1905, wh e re a s t h e in se cticid e u se by a crea ge is sign ifica n t in t h e gr o u p b o r n b e t we e n 1906-1945. Th e m a in lim it atio n s of th e st u d y a re th e u se o f d eat h cert ificate s a s th e sou rce for occu -p a t io n , wh ich m a y b e in a c cu ra t e , a n d t h e cau se o f d e a th , wh ich m ay n o t b e con firm e d .
A Pro p o r tio n al Mo rtality Rat io (PMR) a n a l y-sis a m o n g 28,032 m a le fa rm e r s, age d 20 ye a r s o r m o re w h o h a ve d ie d b e t we e n 1950-78 wa s co n d u ct e d in Br it ish Co lu m b ia , Ca n a d a (Ga l-la gh e r e t a l., 1984). Ca n ce r e xce ss we r e fo u n d f ro m s t o m a ch , lip , a n d le u ke m ia . A n e w fin d -in g wa s th e e xcess risk for a p last ic a n em ia , n ot st at istically sign ifica n t, a m on g t h e d e a th s fro m th e 1950- 59 p e ri o d .
CANCER RISK IN DEVELO PING CO UNTRIES 9 1
Cad. Saúde Púb lic a, Rio de Jane iro , 14(Sup . 3):87-98, 1998 A c as e co n t ro l st u d y w a s re p o r t e d (Sc h u
-m a c h e r, 1985) b a se d o n d at a fro -m c an ce r re g-i s t r y fro m t h e s t a t e of U t a h , U SA. Ca s e s we re d e fin e d a s wh it e m ale s a ge d 35 ye a rs o r o ld e r wit h a n o n -Ho d g k i n ’s lym p h o m a wh o d ie d d u r in g t h e 1967-82 p e rio d . St ra t ifie d a n alys is wa s d o n e t a kin g in t o a cc o u n t fa r m e rs a n d n o n - f a rm e rs o c cu p a t ion , age -c a t e gor y, a n d d a t e o f b irt h . A s ign ifica n tly h igh risk for n o n -Ho d g k i n’s lym p h o m a w as fo u n d fo r fa rm e r s w h o se d ia gn o s e s w e re m ad e d u rin g t h e ye a r s 1952-71, b u t n o t fo r t h o se d ia gn o se d a ft e r 1977. Ly m p h o c i t yc lym p h o m a wa s t h e m a jo r d iagn o sis ce ll t yp e.
Fin d in gs fro m a Ne w Ze a la n d Ca n c e r- re g-i s t ry b a se d ca s e -co n t ro l st u d y g-in vo lvg-in g m a le leu kem ia pa t ie n ts re g i s t e re d d u r in g 1979-1983, age d 20 ye a rs o r m o re a t t im e o f re g i s t ra t i o n we re r e p o rt e d (Pe a r ce e t a l., 1987). Agr i c u l-t u re / f o re s l-t ry/ fish in g w orkers ca l-tego ry p re s e n l- t-ed th e m ost sign ifican t e xc e s s, wh en com p a re d wit h t h e o t h e r la b o r ca te go r i e s. Mo re d e t aile d an a lys is o f t h e o c cu p a t io n s fr o m t h e a gri c u l-t u re / f o re s l-t ry/ fish in g ca l-t e go r y sh ow a s l-t a l-t isl-t i-ca l s ign ifii-ca n t e xc e ss o f le u ke m ia a m o n g t h e l i ve sto ck fa rm gro u p . No ca se s we re id en t ifie d a m on g th e p o u lt ry fa rm wo rk e r s.
In t h e Ne w Ze a la n d n o n Ho d g k i n’s lym -p h o m a e xce ss (Pe a rce e t a l., 1986), it was fo u n d th at a gri c u l t u ra l wo rke rs we re a t in cre ased ri s k o f d e ve lo p in g m a lign a n t lym p h o m a . Si m i l a r e xc e s se s h a ve b e e n fo u n d in s t u d ie s in o t h e r c o u n t ri e s. So m e o f t h e se st u d ie s fo u n d a n a s -so c ia t io n b e t we e n m a lign a n t lym p h o m a a n d e x p o s u re t o p h e n ixyl h e rb icid es o r ch lo ro p h e -n o l s.
As a n u p d at e of t h e p re vio u s st u d y, (Pe a rc e e t a l., 1987), in t e r vie ws we re c o n d u c t e d wit h p a t ie n t s fro m t h e n o n -Ho d g k i n’s lym p h o m a o t h er t h a n lym p h o sa rcom a a n d re t i c u l o s a rc o m a gro u p . Da ta from t h e in te rviews we re n e ga -t i ve fo r a n y a ss o cia -t io n b e -t we e n in s e c -t icid e s an d t h e d is e a se s. H owe ve r, it w a s su gge s t e d t h a t t h e ove ra ll e xc e ss risk fo r far m e rs wa s a t -t r ib u -t a b le -t o e xc e ss a m o n g fa rm e rs w h o h a d c a r ried ou t fen cin g wo rk o r b ee n em p loyed in a m e a t p ro ce s sin g wo rk. Th e a u t h o rs d iscu sse d t h e n e e d fo r co n sid e rin g t h e p o t e n t ia l ro le o f zoo n otic on co ge n ic viru s in th e e tiolo gy o f m a-lign a n t lym p h o m a a m o n g e xp o se d p eo p le a n d w o rk e r s. It wa s p o in t e d o u t t h e fa c t t h at e p i-d e m io lo gica l e vii-d e n ce fo r th e ro le of zo o n o t i c o n c o ge n ic vir u s e s is we a k. Mo st s t u d ie s h a ve b e en e cologica l in n a t u re a n d h a ve n o t in clu d e d s e ro lo gica l t e st fo r e vid e n ce o f vir a l in fe c -t ion . Howe ve r, i-t is n o -t c le a r wh e -t h er su ch -t e s-t w ou ld b e in fo rm a t i ve wit h ou t m o re a d e q u a t e k n o wle d ge o f t h e p o ss ib le m e ch a n ism s o f in
-fect io n . It h a d b ee n su gge ste d th at th e se vir u se s m a y c au sse t u m ors in a n im als wit h o u t sse ro -logical e vid e n ce o f vira l in fe ctio n .
A p ro p o r t io n a t e m o rt a lit y a n a lysis (PM R; Pr o p o rt io n a l Ca n ce r Mo r ta lit y Ra t io – P CMR) o f Wisco n sin wh it e m a le far m e r s, a ge d 18 an d ove r, wh o d ied d u rin g th e years 1968-1976 wa s c o n d u c t e d (Sa ft las e t a l., 1987). Ca n ce r s it e s wit h sign ifica n t ly e le va t e d PMRs in c lu d e d s t o m a ch , p ro s t a t e, e ye, Ho d g k i n’s lym p h o m a , le u ke m ia , lym p h o sa rco m a an d re t i c u l o s a rc o-m a , a n d o t h e r lyo-m p h o o-m a s. Fo r e a ch o-m a jo r a g ri c u l t u ra l a ct ivit y, t h r e e h ie ra rc h ic le ve ls o f in t e n s it y we re ca t e go ri ze d . Alt h o u gh c an ce r e xce ss r isk wa s fo u n d fo r so m e e xp o su re ca t e -g o ri e s, m ain ly h erb icid es, in secticid e s, an d fer-t i l i ze r, n o asso cia fer-t ion wa s fou n d for fer-t h e c h i c k-e n agr i c u l t u ral k-e xp o su rk-e catk-e gory.
O t h e r in ve st iga t o r s (Cu z ick & De St a vo l t a , 1988) st u d ie d m u lt ip le m yelo m a risk fa ct ors by m e an s o f a n e xp lora t o ry case-co n trol st ud y. Alt h o ugh m u lAlt ip le m yelo m a is re p o rAlte d Alt o b e in -c re asin g in m o st p ar ts of th e w orld , ve r y litt le is k n own a b ou t it s e tiology. Fa rm in g an d agr i c u l-t u re, ra d ial-t io n , a n d a va rie l-t y o f ch e m icals (a s-b e s t o s, a rse n ic , cu t t in g o ils, h e avy m e t a ls , p e t ro c h e m i c a l s, an d m a te rials asso cia t ed wit h p la st ic a n d r u b b e r m a n u fa c t u re ) wh ic h a re su s p e ct e d age n t s, b u t n o n e o f t h e se o b se r va -t ion s are u n eq u ivoca l. In c rea sed risk in le a -th er w o r ke rs a n d wo o d wo r ke r s h a ve a lso b e e n re -p o rte d . Im m u n e s u -p re ssio n is -p o st u lat e d t o b e i m p o r t a n t , p o ss ib ly re s u lt in g fro m ch r o n i c an tige n ic stim u latio n . So m e ia tro ge n ic fa cto rs a re a lso m e n t ion ed a s e t io lo gic. Th e st u d y wa s con d u ct ed in En glan d a n d Wa le s b e twee n 1978 a n d 1984. Ris k fa c t or s st u d ie d in clu d e d o cc u -p ation , ch e m ica l e x-p o su re, ra d iation e x-p osu re, p r ior d ise as e, im m u n iza t io n s, ch r on ic in fe ct ion s a n d m a rkers for d efe cct s in im m u n e re g u -l a t i o n s. Sign ifica n t r is k wit h a gri c u -l t u re a n d foo d p r oc e s sin g wa s ob s e r ve d , b u t c o u ld n o t b e b ro ke n d own t o t h o se e xp ose d t o a n im a ls/ m e a t p ro d u ct s or t h o se e xp o s ed t o p e st icid e s. Sign ifican t e xce sse s we re also n ote d fo r re p o rt-e d rt-e xp osu rrt-es to ch rt-em icals an d gasrt-es/ fu m rt-es.
Cad . Saúd e Púb lic a, Rio de Jane iro , 14(Sup. 3):87-98, 1998
A d eath cert ifica te- b ase d ca se con t rol stu d y wa s p e rf o r m e d (Sc h u m a c h e r & De i ze ll, 1988) t o in ve stiga te asso cia tion s b e twee n occu p a tion a n d No n - Ho d g i n k’s lym p h o m a in No rth Ca ro l i-n a , U SA. Ca se s co i-n s is t e d o f m e i-n w h o d ie d o f NH L d u rin g t h e ye a r s 1968- 70, 1975- 77, a n d 198082. Occu p a t io n a n d in d u st r y we re o b ta in ed fro m t h e d e at h cert i f i c a t e s. No asso cia t ion was fou n d b et we en NHL an d fa rm in g em -p l oy m e n t .
Ba se d o n t h e e xce ss r isks o f lym p h om a s , le u ke m ia , a n d m u lt ip le m ye lom a re p o r te d in a g ri c u l t u ra l wo rk e r s, a ca se -co n t ro l st u d y wa s co n d u cte d (Brown son & Reif, 1988). Cases a n d c o n t ro ls we re id e n t ifie d t h r o u gh t h e St a t e o f Mi s s o u r i De p a rt m e n t o f He a lt h . Ca se s h a d t o b e 20 ye a rs o r old e r d u r in g 1984 a n d 1985. A s ign ific an t e xc e ss a m o n g fa r m e rs wa s fo u n d fo r a cu t e lym p h a t ic le u ke m ia a m o n g t h o se w h o d ie d yo u n ge r t h a n 65 ye a r s, a n d re t i c u -l o s a rco m a a m o n g t h ose a ged 65 o r o -ld e r.
Th e p rob le m of m u lt ip le e xp o su re s am o n g a g ri c u l t u ral w o rke rs wa s d iscu sse d (Pe a rc e & Re if, 1990). Th e in ve st iga t o rs p oin t e d o u t t h a t s e ve ra l lim it at io n s e xist e d in t h e cu rre n t e p id e m iolo gic al kn ow le id ge o n p o p u la t io n s p o -t e n -t ially e xp o s e d -t o a gr i c u l -t u ral ch e m ic als , su ch as p esticid es, h erb icid es, an d an im al viru s-es th at are p oten tial h u m an carcin ogen s.
Occu p at io n s in agri c u l t u re in De n m a rk t h at s h ow a h igh r isk fo r ca n cer o f t h e lym p h o p oie t-ic s yst e m , Ho d g k i n’s d ise as e, le u ke m ia , a n d m u ltip le m ye lo m a , are am on g th ose wh o en ta il con t act with a n im als (Ro n co e t al., 1992).
In a s t u d y a im e d t o e va lu a t e a gri c u l t u ra l fa ct o rs a n d t h e risk o f m u lt ip le m ye lo m a in e a s t e rn Ne b ra ska , USA, (Za h m & We i s e n b u rg-e r, 1992), a n in c rrg-e a srg-e d ris k w as fo u n d a m o n g wo m e n wh o h a d e ve r live d o r wo rke d o n a f a r m , a n d w h o h a d e ve r u se d in s e c ticid e s o r h e rb icid e s o n t h e far m , w h e n co m p a re d wit h m en . Also, a stu d y of fa rm ers from 23 Am eri c a n st a t es sh ows th a t th is d iffe re n ce is p a rt i c u l a r l y s t ron g in th e cen tra l USA, wh ich is h e avily a gri-c u l t u ra l.
A s t a t ist ic ally s ign ifica n t h igh m a lign a n t m e la n om a excess am o n g Ca l i f o r n ia ve t e ri n a ri-a n s wri-a s re p o rt ed (Fri-a sri-al et ri-a l., 1966).
Th e c a u s e s o f d e a t h a m o n g 1,551 w h it e m ale ve t e ri n a rian s wh o d ied from 1966 t h ro u g h 1977 wa s co m p are d wit h t h e US gen era l p o p u -lat io n t h ro u gh a p ro p o rtio n a te m o rta lit y st u d y ( Blair & Ha ye s, 1980). Mo rta lity was sign ifica n t-ly in cre as e d fo r le u ke m ia a n d Ho d g k i n’s d is-e as is-e a s wis-e ll as c is-e rt a in o t h is-e r t yp is-e s o f c a n c is-e r : ca n ce r o f skin , a n d ca n ce r o f b rain an d cen tra l n e rvo u s s ys t e m . Mo rt a lit y fro m le u ke m ia a n d Ho d g k i n’s d ise a se wa s st a t is t ic a lly sign ific an t
a m on g p racticin g ve t e ri n a rian s b u t n o t fo r th e n o n - p ra c t i t i o n e r. Po t en tia l e xp o su re s t o p e st i-c i d e, io n izin g ra d ia tion (d u e to lai-ck of safe ty in th e u se o f Xrays e q u ip m e n t), an d zo on o tic a n im a l viru se s we re d iscu sse d , a lt h o u gh n ot sta -tist ica lly t este d , as th e p o ssib le e tiologic fact ors to e xp la in t h e ir fin d in gs.
Ve t e ri n a r ia n s m o rt a lit y w a s s t u d ie d b y m e a n s o f a co h o rt st u d y in Mi s s o u ri, U SA ( Boot s e t a l., 1966). No sign ifica n t can cer exc e s s we re re p o rt ed .
Th e m o rt a lit y o f 20.000 ve t e ri n a r ian s wa s stu d ie d (Mat a n o ski & Lilien fie ld , 1976). St a t i s t ica lly sign ifica n t St a n d a rd i ze d Mo r t a lit y Ra -tio (SMR) excesse s we re fo u n d fo r ca n cer o f t h e l a rge in t e st in e, p ro s t a t e , b ra in , lym p h a t ic t is su e wh en co m pa re d wit h th e U S ge n eral p op u -l a t i o n .
H igh e r ove ra ll d e a t h r at e s a m o n g Il l i n o i s ve t e ri n a ria n s wa s re p o r t e d wh e n c o m p a re d wit h t h e U S ge n e ra l Po p u lat io n (Sc h n u rre n -b e rge r et a l., 1977).
H owe ve r. re ce n t in ve st iga t io n s on ca n ce r am o n g ve t e ri n a r ia n s d id n o t s h o w e xc e s s (Lin ken , 1983; Mille r & Be au m o n t , 1995).
D i s c u s s i o n
Th e in ve st iga t io n s d e s cr ib e d a b ove a re a n e c -d o t a l re p o rt s, e c o lo gic c o rre la t io n , cro s s s e c-tion al su r ve y s, re g i s t ry-b ased ca se -con t rol, an d p ro p o rtio n at e m o rta lity stu d ies wh ich gen e ra t-e d som t-e h yp o th t-est-es in t ht-e ro lt-e o f ct-erta in t-e n viron m en tal/ occu p at io n a l exp o su re a n d th e o b -s e rvatio n of ca n ce r e xc e -s -s.
H owe ve r, d e fin it e ca u s a l a sso c ia t io n ca n -n o t b e d ra w -n fro m t h o se fi-n d i-n gs. Th e m a jo r lim it a t io n s o f su ch e p id e m io lo gic s t u d y d e sign s a re 1) t h e in a ccu ra t e e xp o s u re a sse s s -m en t wh ich is o fte n asso cia t ed wit h -m iscla ssi-fica t io n of e xp o su re b ia s; 2) t h e p ot e n t ial la ck o f a cc u ra cy fro m t h e re p o rt e d u n d e rlin e d ca u s e o f d e a t h fo r so m e gro u p s o f d is e a se s in th e d eat h ce rt i f i c a t e, m a y b e a n o th e r so u rce o f b ia s; a n d 3) la ck o f co n t rol fo r con fo u n d in g e f-fe ct s fro m e xist in g a ge n t s in t h e e n viro n m e n t u n d e r a p p re c ia t io n , su ch a s in se ct icid e s a n d ra d i a t i o n .
CANCER RISK IN DEVELO PING CO UNTRIES 9 3
Cad. Saúd e Púb lic a, Rio d e Jane iro , 14(Sup. 3):87-98, 1998 Ca n cers Mo rt a lity are t h e re q u e st ed d a t a to b e
u sed a s t h e d e n o m in at o r of t h e e stim at e of in -t e re s-t . I-t is re c o m m e n d e d -t o a d ju s-t -t h e e s-t i-m a te b y se x an d b y a ge gro u p .
Pr o p o r t ion a l m o r t a lit y ra t io ca n b e co n -d u ct e -d wh e n t h e m o rt a lit y se t o f a p o p u la t io n wit h kn ow n e xp o s u re is a va i l a b l e . T h u s, t h e p ro p o rt io n o f ca u se -sp e cific d e a t h s o f in t ere s t in t h e stu d y p op u lat io n can b e co n t ra ste d with t h e p r o p o r t ion o f t h e co r re sp o n d in g c au s e -sp ecific d e ath s in th e gen e ra l p o p u lat io n .
E x p o s u re through vaccine inoculat ion
Th e u se o f ch icke n e m b ryo s in t h e p ro d u c t i o n o f ye l l ow fe ve r vaccin e d u rin g th e Wor ld Wa r II su gge s t e d t h e p re se n ce o f vir u se s c a p a b le o f in d u c in g n e o p la s m in a via n s p e cie s. A ca s e -c o n t ro l m o rt a lit y st u d y a m o n g a rm y ve t e ra n s wa s c o n d u c t e d ( Wa l t e r, 1972) t o d e t e rm i n e wh et h e r th e vaccin e co u ld a lso pro d u ce ca n cer in m a n in re lation t o th eir im m u n iza tion st at u s aga in s t ye l l o w fe ve r d u rin g m ilit a ry se r v i c e. Th e Ye l l ow Fe ver Vaccin a t ion d id n o t sh ow a n y evid en ce o f can ce r exce ss in t ha t in vest iga t io n .
D i s c u s s i o n
Th e p o p u la t io n s fro m t h e d e ve lop in g w o r ld m a y b e p o t e n t ia lly h igh ly e xp o se d t o va c c i n e s p re p a re d fro m c h icke n e m b r yo s a n d e ggs in -fe ct e d wit h t h e p ou lt r y o n c o ge n ic viru s e s. It wou ld b e o f p u b lic h ea lth in te rest to ch a ra c t e r-i ze t h e so u rce a n d t h e t yp e s o f va ccr-in e s t h a t m ay b e in fe cte d , a n d th e m a gn it ud e of t h e p o -t e n -tia l e xp o su re . Also, a n a ly-t ic e p id e m io lo gic i n ve s t i g a t i o n s , a s c as e -co n t r o l s t u d ie s, wo u ld b e su it a b le t o in ve st iga t e w h e t h e r t h e re is a s u g g e s t i ve relat ion sh ip b et wee n in ocu la tio n of in fe ct ed va ccin e an d can ce r e xc e s s. Ca s e c o n -t ro l s-t u d ie s re p o r-t -th e o d d s ra -t i o, i.e., -t h e o d d s o f b e in g a ca se t akin g in accou n t t h e e xp o su re o f in t e r e st , a n d t h e o d d s o f n ot b e in g a ca s e takin g in accou n t t h e exp osu re of in t e re s t .
M eat industry workers re p o rt s
E x p o s u re characterization
Wo rke rs in t h e Me a t In d u s t r y a re h igh ly e x-p o se d t o zo o n o t ic o n c o ge n ic viru se s t h ro u g h th e sla u gh t e ri n g / p roce ssin g in d u strial a ctivity. Howe ve r, t h ose wo rkers m a y b e e xp osed t o ce r-t a in c h e m ica l a ge n r-t s wh e n PVC - w ra p p i n g t a ke s p la c e. PVC film wa s in t r o d u ce d in 1963 an d st ill is t h e m ajo r fresh m eat p acka gin g m
a-t e ria l c u rr e n a-t ly in u se ( Va n d e r vo la-t & Br o o k s, 1977). Th e a m o u n t o f p la st ic m e lt e d o r c o m -b u ste d va rie s con sid era-b ly a cco rd in g to work e r e x p e r ie n ce a n d u se o f p ro t e c t i ve m a t e ria l, an d c o n c e n t rat io n of co n t a m in a n t s va rie s d ire c t l y wit h t h e o p e ra t in g t e m p e ra t u re o f t h e wire ( Sm it h e t al., 1983). PVC w ra p p in g fu m es co n -t a in c h e m ic a l a ge n -t s -t h a-t a re kn own h u m an an d / or a n im al ca rcin o gen ic i.e., b en ze n e, po ly-c yly-clily-c a rom a tily-c h yd ro ly-c a r b o n s, a n d ph th a lat es.
P re l i m i n a ry findings
Fin d in gs fro m En gla n d (Pro p o rtion a te Mo rt a l i-t y Rai-tio-PMR), De n m a rk (Si-t a n d a rd i ze d Mo ri-t a lit y Ra t io SMR), an d Swe d en (St a n d a rd i ze d In -c id e n t Rat io -SIR) su gge s t e d e x-ce ss e s o f lu n g can ce r a m o n g b ut ch ers (Fox e t a l., 1982) in th e p e r iod b et wee n 1961 a n d 1973. A sim ila r exc e s s wa s id e n t ifie d fo r t h e 1959-63 p e r io d in En g-la n d a n d Wa le s (Griffit , 1982). A sim ig-la r e xc e s s w a s fo u n d in Ge rm a n y fo r t h e p e r io d 1954-66 ( D o e rke n & Re h p e n n in g, 1982). H a n d vira l w a r ts a re oft e n fo u n d a m o n g b u t ch e rs b y d e r-m a t o l o g i s t s . Th e wa r t s r-m a y p ro d u c e r-m align ch a n ge a n d a t e n t a t ive a ssu m p t io n wa s m ad e on th e ir ro le to exp lain lu n g can ce r e xce ss ( Pe -gu m , 1982).
A PMR a n a lys is fro m t h e sta t e o f Wa s h i n t on , U SA, w a s p re se n t e d (Milh an , 1982), su g-ge stin g n o lu n g ca n ce r e xce ss am o n g b u t ch ers an d m e a tcu tt e rs.
A m or t a lit y e xce ss o f t u m o r o f t h e h e m a to p o ye t ic/ lym p h a t ic syst e m s a n d t u m o r o f co n -n e c t i ve t issue s w e re re p o rt ed n a PMR n ve s t i-gation am on g m ale cattle an d p ou ltry slau gh ter-h o u se wo rke rs fro m Ba l t i m o re, Ma rylan d , USA ( Jo h n so n & Fish m a n , 1982). Th e au t h o rs a ls o o b s e rve d exce ss m or tality o f ca n cer o f tra c h e a , b ro n c h u s, a n d lu n g, a n d ca n ce r o f t h e b la d d e r. Th e re la t io n sh ip b e t we e n o cc u p at io n a l b u t c h e r e xp o su re a n d lu n g ca n ce r wh ile co n -t rollin g for cigat -te sm okin g by m ea n s o f a rea n rea lysis of rea p re vio u s crea se co n t ro l s t u d y co n -d u c t e -d in t h e 60’s wa s re p o r t e -d ( Ve n a e t a l., 1982). Ca ses we re p at ie n ts a d m it te d to a h osp i-t a l in Bu f f a l o, Ne w Yo rk, U SA. Th e e xc e ss r i s k wa s a ccou n t ed fo r b y ciga ret te sm o kin g.
Cad . Saúd e Púb lic a, Rio de Jane iro , 14(Sup. 3):87-98, 1998
a m o n g t h e jo b -ca t e go r i e s. Th e lu n g c a n c e r SM R fo r t h e skille d w o rk e r s, wh o h a d wo rk e d a n ave ra ge o f 20 ye a rs in slau gh t e rh o u se we re in exc e s s, wh erea s t h e lu n g ca n ce r SMR fo r th e n o n -s kille d wh o h a d w or ke d a n a ve ra ge o f 10 ye a rs in sim ila r wo r k e n viro n m e n t , d id n o t s h owed t h e sam e e ffe ct.
O ccupational cohort s
A h ist orica l coh ort m o rtality stu d y a m o n g m ea t i n d u s t r y wo rke rs w as c o n d u c t e d ( Jo h n so n e t a l., 1986a ) a im e d t o b e t t e r cla r ify wh e t h e r a p o p u la tion h igh ly exp osed to m a n y of t h e se e x-p o s u re s wo u ld x-p re se n t x-p o sit ive fin d in gs u sin g b o t h PMR a n d SMR a n a lysis. Th e st u d y p o p u la t io n wa s se le c t e d fro m m e m b e r s o f a m e a t -c u t t e r’s u n io n in t h e -city o f Ba l t i m o re, St a t e o f Ma ryla n d , U SA. 28,901 p e rso n s we re fo llowe d u p w ith in t h e p e r io d fr o m 1949 t o 1979. To d a t e , t h e Ba l t i m o re m e at c u t t e r’s u n io n co h o rt is t h e m ost t h o ro u gh e p id e m io lo gic in ve s t i g a-t io n on a-t h e a sso cia a-t io n o f zo o n o a-t ic o n co ge n ic v i r use s e xp o su re wit h h u m a n m o rt a l i t y.
Th e in ve st iga t o rs in it ia lly re p o r t e d t h e re -sult from th e white m a le su b -p o p u lation . Ni n e-t y five p ercen e-t of e-th is grou p ha d w orke d in o n ly o n e jo b -ca te go ry lifet im e, a llowin g for a n sep a-rate d ata a n a lysis b y e ach jo b -ca te go ry. Th e e x-p e c t e d n u m b e r o f ca se s w e re d ra wn fro m t h e Ba l t i m o re gen e ra l p op ulat io n ra t e s. Fo r th e en -t i re co h o r -t , s-t a -t is-t ica lly sign ific an -t e xce s s wa s id e n t ifie d for a ll ca n ce rs, ca n ce r o f t h e b u c cal ca vit y an d p h a r yn x, c a n c e r o f la rge in t e st in e , a n d lu n g can cer. Am on g th e 36 o b serve d d e a t h s f ro m t h e Ch icke n -Sl a u g h t e r in g wo rk e r s , t h e o ve ra ll ca n c e r SMR wa s 0.69. No d e a t h s fro m h e m a t o p oye t ic / lym p h a t ic t u m o rs we re o b -s e r ve d . Ca n ce r o f Bu cc a l Ca v i t y, Ca n ce r o f E s o p h a g u s , a n d Ca n ce r o f St o m a ch e xc e s s e s we re b a s e d in o n ly o n e o b se r ve d d e at h e a c h . Wo rke rs fro m Me a t D e p a rt m e n t s o f Gro c e r y St o re s / Su p e rm a r ke t s wh o a ls o m a n ip u la t e c h icke n a n d fowl d id n o t p re s e n t a n y s t a t is t i-cally sign ifican t exce ss can cer risk, e xcep t wit h lu n g c a n ce r w h e n t h e lo s t o f fo llow u p we re w i t h d r a wn fr o m t h e a n alys is s in c e t h e ir la s t c on t ac t , 46 o b se r ve d d e a t h s , 33.92 e xp e ct e d d e a t h s, SMR 1.36, 95%CI (0.99; 1.81), χ23.95.
Th e sa m e in ve s t iga t o rs ( Jo h n so n e t a l., 1986b ) p re se n t e d n e w d a t a fro m a su b -c oh o rt f ro m t h e Ba l t i m o re m e a t c u t t e r ’s u n io n st u d y p re vio u sly d e scrib e d . It wa s t h e firs t a n a lys e s o n t h e m o r t a lit y e xp e rie n ce o f wo m e n wh o w o r k in t h e m e a t in d u s t r y. Co n s i d e ra t io n s o f sp e cific t yp e o f e xp o s u res we re m a d e. Wo m e n in t h e Me a t In d u s t ry t ra d it io n a lly h a ve b e e n w ra p p in g a n d la b e lin g m e a t as a p re d o m i n a n t
t a sk. Th e w ra p p in g fu m e s co n t a in ch e m ica l a ge n t s t h a t a re kn o wn h u m an a n d / o r a n im a l c a rcin oge n ic i.e., b e n ze n e, p o lyc yclic a ro m a t i c h yd ro c a r b o n s, a n d p h t h ala t e s. Th o se wo rk e r s a re also exp o se d to viru ses t h a t n a tu rally ca u se le u ke m ia a n d lym p h o sarco m a in a n im a ls. Ex-p o s u re t o n itro s a m i n e s, a kn own carcin o ge n , is a n o t h e r p o t e n t ia l s o u rce of e xp o s u re a m on g t h e m .
Am on g th e 484 Chicke n Sl a u g h t e rin g worke r s, t h worke rworke wworke rworke 21 o b s worke rvworke d d worke a t h s. Lu n g c a n -ce r p re se n t e d st a t ist ica lly s ign ific a n t e xc e s s ris k, 3 o b se rve d d e a t h s, SMR 4.56. No d e a t h s we re o b se r ved in th e h e m a to p oye t i c / l y m p h a t-ic system s.
Th e 3622 Gro c e ry St o re s / Su p e rm a rket w h i t e wo m e n w o rke r s p re se n t e d e xc e ss fo r a ll c a n -ce rs o f t h e h e m a t o p oye t ic/ lym p h a tic s ys t e m s b ase d in 10 o b ser ve d d e ath s (PMR 2.17, st a t is-tically sign ifican t). Th e sp e cific can ce r sites ex-ce ss we re H o d g k i n’s Lym p h o m a , 1 o b se r ve d d e at h , SMR 1.23; Leu kem ia & Ale u ke m ia , 4 o b s e rved d e ath s, SMR 1.85; an d Can cer o f All Ot h -er Lym p h o p o ie tic Ti s s u e s , 3 o b s -erve d d e a t h s, SMR 2.46. Ca n cer of lu n g wa s also fo u n d in ex-ce ss b a sed o n 14 d eat h s, SMR 1.95, was sta tisti-cally sign ifican t.
Th e m or t alit y ra t e a m on g n o n wh it e m e n s u b c o h o rt fro m t h e sam e Ba l t i m o re m e a t cu t -t e r’s u n io n s-t u d y wa s re p o r-te d ( Joh n so n , 1989). St at ist ica lly sign ific a n t e xce s s for lu n g c a n c e r a m on g wo rke rs in a b a t t o irs, a n d e s op h a gu s can ce r a m o n g wo rke rs in m e a t p ac kin g p lan t s we re fo u n d . No exce sse s occu rred am on g w o rk-ers from Ch icken -Sl a u g h t e ri n g .
CANCER RISK IN DEVELO PING CO UNTRIES 9 5
Cad. Saúd e Púb lic a, Rio d e Jane iro , 14(Sup. 3):87-98, 1998 w rap p in g an d lab elin g in th e m ea t in d u stry h as
b e e n h ist o rica lly d o n e b y wo m e n , a n d t h e ro l e of its fu m es a s a p ot en t ial e t io logic fact o r n ee d f u rth e r in ve s t i g a t i o n .
Th e fin d in gs a ft e r a n a d d it io n a l 9-ye ar fo l-l ow -u p o f t h e p re vio u sl-ly s t u d ie d gro u p o f w o rke rs in ab at to irs an d wo rke rs in m e at-p ack-in g p lan t s wa s r e p o rt e d ( Jo h n so n , 1995). Ex-c e ss r is k wa s fo u n d fo r a ll Ex-ca n Ex-c e r Ex-co m b in e d , can cers of th e lu n g, b u ccal cavit y a n d p h ar y n x , e s o p h a g u s, c olon , b la d d e r kid n e y, a n d b o n e. Of re l e va n t in t e re s t is t h e id e n t ifica t io n o f a f o u r-fo ld sign ifica n t r isk o f lu n g ca n ce r am o n g wh it e -wo m e n wh o se p re d o m in a n t a ct ivit y in t h e m e a t in d u st r y is t h e wra p p in g, la b e lin g, an d p ackin g o f m e a t . In su m m a ry, lu n g can ce r m o rt a lit y in t h e m e a t in d u s t r y is st a t is tic a lly re l e va n t in t h e p h ys ica l a re a s w h e re killin g/ d re ssin g, sm o kin g a n d cu r in g of m e a t , a n d w ra p p in g/ la b elin g activit ie s t oo k p la ce .
Th e m o rt a lit y of t h e s u b -co h or t o f p o u lt r y s l a u g h t e ri n g / p rocessin g worke rs fro m t h e Ba l-t i m o re m e a l-t c u l-t l-t e r’s c o h or l-t wa s in ve s l-t i g a l-t e d ( Jo h n so n e t a l., 1997). Th e in vest iga t o rs fo u n d st at ist ica lly sign ifica n t e xce sse s o f r isk t o can c e r o f t h e e so p h a gu s, live r, p a n c re a s, a n d t u -m ors o f t h e ly-m p h op oiet ic syste -m s, a s a gro u p. In t e re s t i n g l y, t h e re is a n o n -sign ific a n t e xc e s s o f c a n c e r o f lu n g in t h e wh it e m a le s, a n d in wh ite fe m ales.
An o t h e r n e s t e d c a se - co n t ro l s t u d y w a s co n d u ct e d in t h e Ba l t i m o re m e a t cu t t e r’s co -h o rt in o rd e r t o a ssess t-h e re lat io n s-h ip b e twe e n o ccup a t ion al e xp osu re an d d e a th from t um o rs o f th e lym p h op oiet ic syst em s. Sl a u g h t e rin g ac-t iviac-t ies in vo lvin g h e a vy e xp o su re ac-t o o n co ge n ic v i ru se s we re st r o n gly as so cia t e d wit h lym -ph op oie tic tu m ors, esp ecia lly with lym p h o m a s. Wo rke r s in c h ic ke n s la u gh t e r i n g / p ro c e s s i n g p la n t s p re se n t e d a n o d d s ra t io o f 2.8, 95% CI (0.8- 9.5). Am o n g t h e su p e rm a r ke t wo r k e r s, w ra p p in g m ea t wa s a sso cia t e d wit h in cre a s e d risk o f ca n cer o f lym p h o p o iet ic tissue s, OR 3.8, 95% CI (1.0-14.3). Also, m e a t cu t t in g in su p e rm a rke t s wa s a s so cia t e d wit h rm u lt ip le rm ye l o -m a in -m a les, OR 18; 95% (CI 1.6-207.5).
T h e re a re re p o r t s o f a n a lyt ic a l e p id e m io -lo gic in ve st iga t ion s in wo rke rs from t h e m e a t i n d u s t ry ot h e r t h a n t h e Ba l t i m o re m e a t wra p -p e r’s co h o rt . A fo llo w-u -p s t u d y ca rrie d o u t in En glan d (Co ggo n e t a l., 1989) re p o r t e d s t a t is-t ica lly s ign ific a n is-t lu n g c a n c e r e xc e s s ri s k a m o n g b u tch e r wo rk e r s. Th e exce ss w as gre a t -e st a m on g t h os -e wit h t -e n or m o r-e y-e a r s o f -e p o s u re a n d in te re s t i n g l y, o n t h o se wo rke rs e x-p o s e d t o re c e n t ly sla u gh t e re d m e at (wa rm m e a t ). To b a c co e ffe c t w a s n o t c o n t ro lle d . A h i s t o rica l co h o rt wa s c o n d u c t e d in Ge n e va ,
Sw i t ze r la n d , (Gu b e ra n e t a l., 1993) a m on g a ll s e lf e m p lo ye d b u t ch e r s b o rn sin ce 1880 w h o s e t u p a sh o p fro m 1901 t o 1969, a n d t h e ir w i ve s. Th e s t u d y gro u p w a s follo we d u p fro m 1901 t o 1990 for ge n eral m o rt a l i t y, from 1942 t o 1990 fo r c a u se sp e cific m o rt a l i t y, a n d fro m 1970 t o 1989 fo r in cid e n ce o f c a n c e r. Am o n g c a n c e r s, t h e re we re sign ifica n t e xc esse s in t h e in cid e n c e a n d m o rt a lit y fr o m co lo re ct a l c a n -c e r, -ca n -ce r of t h e p ro s t a t e , an d in in -cid en -ces o f l i ve r c a n c e r. Th e r isk o f lu n g ca n c e r wa s in -c re a se d fo r p o rk b u t -ch e r s. A -clu s t e r o f d e a t h s o f le uke m ia w as id en t ified a m on g old er b u t ch -e r s , wh o w-e r-e b o r n la s t c-e n t u r y. O f in t -e r-e st is t h e ob se r va t ion t h at th e ca se s of le u ke m ia are re la t e d t o p e rs o n s wh o sla u gh t e r e d a n im als, t a sk p erf o rm ed b y b u tch e rs u n t il 1949.
Most re c e n t l y, we fo u n d can ce r e xce ss in a h i s t o rica l coh ort of 7,700 wo rkers fro m p o u ltry s l a u g h t e ri n g / p r oc e s sin g p la n t s in Mi s s o u ri , U SA (Net t o & Jo h n so n , 1998, in p re ss). Ca n c e r o f b ro n c h u s, t rach e a & lu n g an d ca n ce r of kid -n ey p re se-n te d st at istically sig-n ifica -n t exc e s s. A p o s i t i ve d o se re sp on se re lat io n sh ip was fo u n d fo r ca n ce r o f b ro n c h u s, t r ac h e a & lu n g, a n d c a n c e r o f t h e kid n e y b y m e a n s o f la t e n c y a n d d u r a t io n o f e m p loym e n t an a lysis. To a le ss e r e xt en t, som e can ce rs o f th e lym p h op oiet ic syst e m w e re a lso fo u n d e xc e s s i ve : Ly m p h o s a rc o -m a &a-mp; Re t i c u l o s a rco-m a , Leu ke-m ia &a-mp; Aleu ke -m ia , a n d Ca n c e r o f All Ot h e r Lym p h o p o ie t ic Ti s-s u e s-s. Se ve ra l ot h e r ca n cers-s we re a ls-so exc e s-s s-s i ve, s u ch a s c an ce r o f s t om a ch , ca n c e r o f la rge in -t e s -t i n e , ca n ce r o f p a n cre a s, ca n ce r of b la d d e r, can cer o f ce r vix, ca n ce r o f t h yro id , an d c an ce r o f ce n tra l n e rvou s syst em .
D i s c u s s i o n
Th e fin d in gs fro m t h e se ve ra l in ve stiga t ion s in m eat in d u st ry coh o rts h a ve sh own th at t h e re is a sugge st ive rela t ion sh ip b e twee n occu p a tio n -a l e xp o s u re in t h e c h icke n s l-a u gh t e ri n g / p r o-ce ssin g in d u st ry a n d can o-ce r exc e s s, p a rt i c u l a r-ly o f lu n g ca n ce r a n d ca n c e r of r-lym p h o p o ie t ic t i s s u e s.
An a lyt ic e p id e m io lo gic in ve st iga t ion s in w o rkers from t h e p o u lt ry in d u st ry in t h e d e ve l-o p in g cl-o u n trie s shl-o u ld b e cl-on sid e red , in l-ord e r t o h e lp to elu cid at e whe th er th eir occu p ation a l p o p u latio n s wh o a re h igh ly exp o se d t o p ou ltr y o n co gen ic viru se s also p re se n t ca n ce r risk e x-c e s s, p a rtix-cu la rly x-can x-ce r o f lu n gs an d x-can x-cer o f lym p h op o ie t ic syste m s.
Cad . Saúd e Púb lic a, Rio de Jane iro , 14(Sup. 3):87-98, 1998
p o p u la t io n . Th e e st im a t e o ft e n u s e d in re t ros p e c t i ve, o r h irost o rical co h o rt ros, iros th e rostan d ard -i ze d m o rt a l-it y ra t -io – SMR. Th e SMR st a t -ist-ic s is a ca u se - sp e cific m o rt a lit y r a t e in t h e st u d y p o p u la tion (n u m erat or) co n tra st ed with th e res p e c t i ve m o rt a lit y ra te in a co m p a r ireso n p o p u -lat io n (d en o m in a to r).
Th e p os sib ilit y t o c o n d u c t h ist o rica l co h o r t s w ill d e p e n d o n t h e a va ila b ilit y o f e xp o -s u re re c o rd -s, a n d re lia b le in fo r m a t io n o n t h e w o rke rs vita l sta tu s th rou gh t he closin g d at e o f t h e follo w - u p . Als o, in o rd e r t o c o m p u t e t h e SMR, m o r t alit y ra t e s fro m t h e co m p a r i s o n p o p u la t io n , ad ju st ed by a ge gro u p s a n d ca le n -d ar p erio -d s n ee -d to b e ava i l a b l e. Gi ven th at th e s u s p e ct e d c a n ce rs a re re l a t i ve ly ra re e ve n t s, t h e p owe r o f t h e p ro s p e c t i ve in ve s t i g a t i o n s m u st b e co n sid e re d . Fu rt h e rm o re, d e p e n d in g o n t h e ch ara c t e rist ics o f t h e ch icken in d u st ri a l p r o ce s s in d e ve lo p in g co u n t r i e s, t h e re is t h e n ee d t o a ssess t h e ro le of p o t en t ia l co n cu rre n t ch e m ica l exp osu re in can cer ri s k .
C o n c l u s i o n s
A t h o ro u gh re vie w o f t h e p u b lish e d wo rks o n t h e p u t a t ive r e la t ion s h ip b e t we e n p o u lt r y o n c oge n ic viru se s an d can cer m o rt alit y is p
re-se n te d . Th e m a jo r it y o f t h e ava ila b le d at a wa s d raw n fro m e p id e m io lo gic in ve st igat ion s co n -d u c t e -d o n p o p u la t io n s in t h e U S a n -d Eu ro p e . Alt ho u gh in con clusive l y, th e lit era t u re su ggests t h a t t h e p o u lt r y o n c o ge n ic vir u s e s m ay b e a ris k fa c t o r o f ca n ce r for t h e h u m a n p o p u la -t i o n s. Ca n cer of Bro n c h u s, Tra ch e a & Lu n g, an d Ca n ce r o f Lym p h o p o ie t ic Sys te m s h a ve b e e n con sist en t ly fou n d in exc e s s.
Th e in t e n sit y of e xp o s u re t o p o u lt ry on co -ge n ic vir u se s in t h e -ge n e ra l p o p u la tio n o f t h e d e ve lo p in g co u n t rie s m a y b e q u it e d iffe re n t t o th at cu rren t ly o b ser ved in th e d evelop ed co u n -t ri e s. Th is p a p e r a d d re ss e s -t h e p u b lic h e a l-t h re l e va n c e t o in ve s t iga t e w h e t h e r t h e p o p u la tion s fro m t h e d evelop in g co u n tries wou ld p re -se n t sim ila r ri s k .
Q u e st io n s t o b e a n sw e re d a re : 1) w h e t h e r p o p u la tio n s from d e velo p in g cou n tri e s, p a rt i cu larly t h o se from rcu ral a re a s, e xp e rien ce h igh e r in t e n s it y o f e xp o su re t h a n t h e co rre s p o n d -in g p o p u lat io n s o f t h e d e ve lo p e d co u n t rie s; 2) w h e t h e r t h e p o p u la t io n s fr o m d e ve l o p i n g c o u n t rie s h ave h igh er e xp osu re to va ccin e s in -fe ct e d wit h t h e p o u lt ry o n co ge n ic viru se s; a n d 3) w h et h e r th e occu p a t ion a l exp o su re t o p ou lt ry on co ge n ic vir u se s in lt h e d e ve lo p in g cou n t rie s is cu r ren t ly h igh e r t h a n t h a t fro m t h e d e -velop e d cou n t ri e s.
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