Cad . Saúd e Púb lic a, Rio de Jane iro , 14(Sup. 3):193-198, 1998
Lung cancer and arsenic exposure in drinking
water: a case-control study in nort h e rn Chile
Cánc e r d e p ulmó n y e xpo sic ió n a arsé nic o
e n e l ag ua p o tab le : un e studio d e c aso s
y c o ntro le s e n e l no rte d e Chile
1 Gru p o p ara el De s a r rollo d e l a In vest i gaci ón en Sal u d (GR EDIS). Casil la 527 50, C o r re o Ce n t ra l , S a n t i a g o, C h i l e . 2 De p a rt am en to Es t a d í s t i c a , Fa cu lt ad d e M a t e m á t i c a s , Po n ti fici a Un i ve r s i d a d Cat ól ica d e Ch i le. Vicu ñ a M a c k e n n a ,4 8 6 0 , San t iago 22, Casilla 306, C h i l e . 3 Facu lt a d de Ci e n c i a s Físicas y M a t e m á t i c a s , Un i v ersid a d d e Ch ile. Av. Bla n co En c a l a d a ,2 1 2 0 , 4op iso of. 1 7 ,S a n t i a g o, C h i l e . Ca t t erin a Fe r recci o 1 Cla u d ia Gon z a lez Psych 1 Vi v ia n M i losa v j lev i c St a t 1 Gu i llerm o M a rsh a ll Gred is 2 An a M a ría San ch a 3
Abstract In som e Ch i lea n cit ies, l e v els of a rsen ic (As) i n d ri n k in g w a t er rea ch ed 800 µ g/L b e-t w een 1950 a n d 1970, w h i le cu rren e-t lev els a re 40 µ g/L. To ev a lu a e-t e e-t h e ca u sa l role of e-t h i s ex p o-s u re i n lu n g a n d bla d d er ca n cero-s, w e con d u ct ed a ca o-se-co n t rol o-st u d y i n Regio n o-s I, I I , a n d III of t h e co u n t ry. From 1994 t o 1996, ca ses d ia gn o sed a s lu n g ca n cer a n d t w o h osp i t a l con t ro ls w ere e n t e red in t h e st u d y; on e con t rol w a s a p a t ien t w it h a can cer, w h ile t h e ot h er w a s a p a t ien t w it h -ou t can cer, b ot h co n d it io n s u n rela t ed t o As . C o n t rols w ere m at ch ed w it h ca ses by a ge a n d sex . A s t a n d a rd su rv ey con t ai n in g q u est ion s ab ou t re s i d e n c e , e m p l oy m e n t , h ealt h h ist ory, w as a d m in -i s t e red t o st u d y su bj ect s. D a t a o n As co n cen t ra t -ion s -i n w a t er w ere o bt a -i n ed from re c o rds of t h e m u n icip a l w a t er com p a n i es. A t ot a l of 151 lu n g ca n cer ca ses an d 419 co n t rols (167 w it h ca n cer a n d 242 w it h o u t ca n cer) w ere en ro l l e d . M ed i a n lev el o f li fet i m e As ex p o s u re w a s sign if ica n t l y h igh er a m on g ca ses, w it h a clea r d o se-resp on se rela t i on sh ip b et w een m ea n As ex p o s u re lev e l s , w it h a n OR (95% CI) of: 1 , 1.7 (0.5-5.1), 3.9 (1.2- 13.4), 5.5 (2.2-13.5), a n d 9.0 (3.6- 22) f o r st ra t a o n e t o five re s p e c t i ve l y. Th is stu d y p rovid es n ew evid en ce t h at As in d rin k in g w a t er can ca u se in -t ern a l can cers a n d giv es a n es-t im a-t e of -t h e form of -t h is re l a -t i o n s h i p .
Key words Lu n g N e o p l a s m s ; En v i ron m en t al Ex p o s u re ; Ar s e n i c
Resumen En a l gu n a s ciu d a d es d e Ch i le, e n t re 19 50 y 1970 , lo s n i v eles d e a rsén i co (A s) en el a gu a p ot a ble a lcan z aro n lo s 800 µ g/l, est a n do h oy en 40 µ g/l; p a ra ev alu a r el rol d e est a ex p o s i-c i ó n , se llev ó a i-cab o est e est u d io d e i-ca sos d e i-cá n i-cer d e p u lm ó n y i-con t roles en la s Region es I, II y I I I . En t re 1994 y 1996, se in gre s a ron ca so s d e cá n cer d e p u lm ón y dos con t roles h osp it a larios: u n c o n t ro l , u n p a cien t e con cán cer y el ot ro , u n p a cien t e sin cán cer, a m bos d ia gn óst icos n o re l a c i o-n a d os co o-n a rséo-n i co. Los co o-n t roles f u eroo-n p a rea d os gru p a lm eo-n t e p o r ed a d y sex o coo-n los ca sos. A ca d a su jet o, se le a p li có u n a en cu est a est a n d ariz ad a so bre re s i d e n c i a , em p leo y sa lu d. La in for-m a ció n sobre n iv eles d e As en el a gu a p rovin o d e re g i s t ros de la s co for-m p a ñ ía s de a gu a . Se in gre s a-ron 151 ca sos d e cá n cer p u lm o n ar y 419 co n t roles (167 con cá n cer y 242 si n cán cer). La m edia n a d e A s en el a gu a p ot a b le a lo la rgo d e la v i d a fu e sign i fi ca t iv a m en t e m a yo r en t re los ca sos, c o n u n a cla ra rela ción d o sis- resp u est a en t re el p rom ed i o d e As y el riesgo, con O R (95% IC) d e 1, 1 , 7 ( 0 , 5 - 5 , 1 ) , 3,9 (1,2-13,4), 5,5 (2,2-13,5), y 9,0 (3,6-22) p a ra los est ra t os 1 al 5, re s p e c t i va m e n t e . Es t e est u di o p rovee n u ev a ev id en ci a sobre el ro l ca u sal d el As en el a gu a p ot a ble en cán ceres in t ern os y sob re la form a de la rela ció n en tre ex p osición y riesgo d e cán cer.
Cad . Saúde Púb lic a, Rio de Jane iro , 14(Sup. 3):193-198, 1998 I n t ro d u c t i o n
Hu m an s a re exp ose d to o rga n ic a n d in org a n i c a rs e n ic (As) fro m e n viro n m e n t a l an d o ccu p a-t io n al sou rc e s. Th e m ain sou rce of exp o su re (in t e rm s o f n u m b er of p eo p le affecte d ) is en viro n -m e n t a l, n a t u r ally o ccu r r in g in o r ga n ic As in d rin kin g w at e r (He sse e t al., 1990; Ba t e s e t a l., 1995). Occ u p a t io n a l e xp o su re a ffe c t s wo rk e r s e n ga ged in sm eltin g a n d refin in g cop p e r, go ld , a n d lead ore s an d in th e p ro d u ction of agr i c u l-t u r al p e sl-t ic id e s, p igm e n l-t s, d ye s, gla ss, s e m ic o n d u ic t o r s, a n d va rio u s p h a rm a ice u t iica l su b s t a n c e s, in clu d in g th e p ossib ilit y of h igh e xp o -s u re t o a irb o rn e a r-se n ic ( W H O, 1981). Ar-se n ic h a s b e e n im p lic a te d a s o n e o f th e m a in r i s k factors for skin , lu n g an d b lad d er ca n cer d e a t h s in n o rt h e r n Ch ile , wh e re re s id e n t s h a ve u se d w at er with h igh As con t en t fo r d e ca d e s. In t h is regio n , b e sid e s t h e n a tu rally occu rr in g a rsen ic, c o p p e r sm e lt in g h as b e e n im p lica t e d as a r i s k fa cto r fo r worker s (Fe r reccio et a l.,1995).
Th e a im o f th is st u d y is t o asse s s t h e d o se -re sp on se -re la t io n s h ip b e t w e e n m e a n a rs e n ic e x p o s u re in d r in kin g wa t e r a n d r isk o f lu n g ca n ce r a m on g resid e n t s in n ort h e rn Ch ile.
M aterial and met hods
Study are a s
No rt h e rn Ch ile in clu d es Regio n s I-III. Th is are a c o n t a in s t h e At ac a m a De s e rt , kn own a s t h e m in in g zo n e of th e co u n try. Th e d ese rt is 1,700 km lo n g an d a n a ve ra ge of 300 km wid e, with a p o p u lat io n o f 900,000. Th e m a in o cc u p a t io n s a re re la t e d t o t h e m in in g a n d fis h in g in d u s-t ri e s. Th e h igh e ss-t exp osu re s-to arsen ic h a s b e en in Re gio n II, t h ro ugh d rin kin g wate r.
M e a s u rement of exposure
Wa t e r c o m p a n ie s s u p p ly t h e re gio n wit h we l l o r su r fa ce wa t e r. Th e y su p p ly t h e s a m e wa t e r t o a ll h o u se h o ld s in a give n city. In t h e s e re -g i o n s, 100% o f t h e u r b a n h o u s e h o ld s a re cov-e rcov-e d b y t h cov-e m u n ic ip a l w at cov-e r u t iliticov-e s syst cov-e m s. Th e u t ilit ie s c o m p a n ie s a re re q u i re d t o p e rf o r m d e t a ile d ch e m ic a l t e st s o rf t h e wa t e r, in -clu d in g As le ve l s , a t le a st o n ce a ye a r. We c o l-le ct e d d a t a o n As l-le ve ls fro m 1950 t o 1996 fo r t h e 350 co u n t ie s fro m t he e n t ire co u n try.
Identification of lung cancer cases
Nu rse s we re re c ru ited fo r th e stu d y an d tra i n e d in in terviewin g tech n iq u es in each city of n orth -e rn Chil-e (Ar ica , Iq u iq u -e, Co p ia p ó, An t o fa gas-ta ). Th ey we re re sp o n sib le for id en t ifyin g ca ses in t h e h o sp ita ls. In t h e m a in h o sp it a ls, in t e rv i e wers m ad e d aily rvisit s t o th e a d m ission s d e -p a rt m e n t s a n d t o -p a t h o lo gy la b o ra t o r ie s t o id e n t ify a n y p a t ie n t s a d m it t e d w it h lu n g ca n -c e r. Pa tien t s n o t id e n tified u n til afte r d is-ch arg e we re visit e d a n d in t e rv i e we d in t he ir h om es.
Eligib le cases we re a ll th ose d ia gn o se d with lu n g ca n ce r in t h e s t u d y re gio n b e t we e n No ve m b er 1994 a n d Ju ly 1996, co n firm ed by b io p -s y, an d wh o -se fir-st d ia gn o -si-s wa -s e it h e r at t h e c u r re n t h o sp it a liza t ion , or n o m o re t h a n o n e yea r b e fore th e cu rren t h o sp it a liza t ion .
Select ion of contro l s
Two co n t ro ls we re s e le ct e d fo r e ac h lu n g c a n -ce r ca s e fro m p a t ie n t s a d m it t e d t o h os p it a ls w it h in o n e m o n t h of t h e in d e x ca s e. Th e first c o n t rol (fo r co n t ro l gro u p A) was se lecte d fro m p a t ie n t s wit h a n o t h e r ca n c e r, u n re lat e d t o ar -se n ic (Sm it h e t a l., 1988). Ca n c e r s o f t h e live r, skin , kid n e y, b la d d e r, a n d p ro s t a t e we re e x-clu d e d . Th e se co n d co n t ro l (for c on t ro l gr o u p B) was se lect e d fro m p a tie n t s with a d ia gn o sis u n relat ed to arse n ic a n d e xclu d in g ca n ce r. Pa-tie n t s a d m it t e d w it h ca rd i ova s c u l a r, s kin , o r n e u ro lo gica l co n d it io n s we re e xclu d e d . Co n t rols we re n ot m a tch ed by h osp it al, sin ce exp o -s u re i-s clo -se ly re lat e d t o t h e re gio n in wh ic h p a t ie n t s re sid e d . In st e a d , e ligib le con t ro ls in -clu d e d all p at ien t s ad m it t ed t o a n y h o sp ita l in th e wh ole stu d y region . Th e n um b e r o f p at ie n ts a d m it t e d t o e a ch h o sp it al in 1994 w a s first id e n t ifie d , an d a fre q u e n cy d ist r ib u t io n of n u m b e rs of a d m is sio n s b y h osp it al wa s ca lc u -la t e d . Co n t ro ls we re se le c t e d t o re su lt in t h e sa m e fre q u e n cy d ist r ib u t io n a s t h o s e fo r a d -m i s s i o n s. T h u s , fo r e a c h in d e x c a se a co n t r o l was s e le c t e d a s a h o sp it a l a d m iss io n wit h in a m o n t h o f t h e in d e x ca s e, of t h e s a m e se x an d with in fou r yea rs o f t h e case’s a ge.
Data collection
Cad . Saúd e Púb lic a, Rio de Jane iro , 14(Sup. 3):193-198, 1998 (lo okin g fo r As -re la t e d le s io n s) a n d re v i e we d
clin ica l re c o rd s to regist er a ll o th er h ealt h co n -d i t i o n s.
A let ter of co n se n t was rea d to all st u d y su b -j e c t s, e xp la in in g t h e m e t h o d o f t h e s t u d y a n d th e ge n eral ob jective. On ly th o se wh o accep te d an d we re a b le t o a n swe r t h e o n e -h o u r in t e r-view we re in clu d e d in th e st u d y.
St atistical analysis
Ar se n ic Ex p o s u re : Hi s t o r ie s o f re sid e n t ial an d w o rk a d d re s se s we r e u se d to d e ri ve m e a n a r-se n ic c o n c e n t ra t io n in d r in kin g wa t e r. T h i s life t im e a ve ra ge wa s t h e m e a n le ve l a cro ss a ll re sid e n t ia l le ve ls a n d p e r i o d s. Life t im e As e xp o s u re was a n a lyzed a s a con t in u o u s an d ca te -g o rica l va ri a b l e , wh e re 5 e xp o su re st ra t a we re d e ve lo p e d b a s e d o n s u b je c t d is t rib u t io n . T h e l owe s t e xp o su re c at e go r y wa s u s e d a s a re f e r e n ce to d e ri ve Od d s Ra t io s (ORs) u sin g u n co n d it io n a l re g ressio n an alysis w ith t h e Sta t a Pro -g ra m . ORs we re e st im a t e d wit h u n iva r ia t e as well a s m u ltiva ria te m od els, con t ro llin g b y a ge, se x, SES, sm o kin g, an d o cc u p at io n a l h ist o r y. Re su lts fro m skin tests we re com b in e d with d at a fr o m m e d ica l re c o rd s at o class ify sat u d y su b -je ct s in 4 cat ego ries: n o le sio n s, p igm en ta t io n , k e ra t o s e s , an d s kin ca n ce r. An a lys e s we re re -p e at e d se -p a ra t e ly fo r e a ch t y-p e o f c o n t ro l. A s e p a r at e m o d e l w a s d e r i ve d fo r wo m e n a n d m e n . A t e st fo r t re n d wa s d o n e b a se d o n Co c h ra n (1954).
R e s u l t s
Du rin g t h e 20 m o n t h s o f e n ro llm e n t , 217 n e w lu n g c as e s we re d ia gn o se d in t h e h o s p it a ls. A t ot al o f 151 (70%) h a d co m p le te in for m a tio n t o e n te r in t o t h e s t u d y. T h e re we re ve r y fe w re -fu sa ls a m on g cases an d co n tro ls (le ss th an 5%). Th e m a in re a s o n s fo r n o t e n t e rin g t h e st u d y we re t h at t h e p a t ie n t s we re n o t a t t h e h o sp it a l a t t h e m o m e n t we at t em p t e d t o con t act t h e m , h a d m oved , or we re t oo sick to fill o u t t he q u e s-t i o n n a i re. A s-t o s-t a l o f 419 c o n s-t ro ls e n s-t e re d s-t h e s t u d y, a ch ie vin g t h e go a l o f o n e co n t ro l p e r c as e fo r t yp e B co n t ro ls (252; 0.9 co n t ro ls p e r ca se) b u t n o t fo r t yp e A co n t ro ls (167; 0.6 co n -t ro ls p e r ca se).
Life t im e m e an As e xp o su re in ca s e s a n d c o n t ro ls is p re se n t e d in Ta b le 1. Th e d a t a a re a r ran ged in five exp o su re st rat a, a n d cru d e a n d a d ju st e d O Rs a re give n fo r e a c h st r at u m . Ad ju st e d ORs we re o b t a in e d w it h a lo gis t ic a l re -g re ss ion m o d e l (St at a ) in clu d in -g se x, a -ge, a n d sm o kin g sta t u s.
T h e re is a cle ar d o se- re sp o n se re l a t i o n s h i p ( Co c h ra n e t e st p <0.05) t h a t is s t ro n ge r wh e n a d ju st e d b y age, se x, an d sm okin g s ta tu s (e ve r o r n e ve r ). O R e s t im a t io n s r e ac h e s st a t ist ic a l sign ifica n ce wh e n As co n ce n t rat io n wa s a b ove 0.03m g/ l. Wh e n c o n t ro l A was u se d a s t h e re f-e rf-e n cf-e gro u p , t h f-e ORs wf-e rf-e f-e vf-e n h igh f-e r t h a n wit h con t rol B ( Ta b le 2). Ne ve rt h e l e s s, b o th e x-p re ss t h e sa m e t yx-p e o f e ffect. Most of th e an a ly-sis was d o n e wit h com b in e d co n tro l s.
Wh e n m a le s a n d fe m ale s we re a n a lyz e d s e p a ra t e l y, m a le s sh owed h igh e r an d m ore sig-n ifica sig-n t ORs : 1,2.2 ( 0 . 6 - 8 . 7 ), 4.1 ( 0 . 9 - 1 7 ), 7.1 ( 2 . 3 - 2 1 ), an d 9.7 ( 3 . 2 - 2 9 )fo r st ra ta 1 th ro u gh 5, re s p e c t i ve l y, com p ared with fem ales: ORs: 1,0.9 ( 0 . 1 . - 6 . 3 ), 3.6 ( 0 . 4 - 3 2 . 6 ), 2.7 ( 0 . 5 - 1 4 . 1 ) ,a n d 7.1
Tab le 1
Life time arse nic le ve ls in d rinking wate r fo r lung case s and co ntro ls. Ave rag e As 1 93 0-19 94.
M ean (mg/ L) C o n t rols (N :4 19) Cases (N:151) O R (cru d e ) OR adjusted (95 % C I)
0 - 0 . 0 1 7 0 6 1 1
0 . 0 1 - 0 . 0 2 9 6 8 9 1 . 5 1 . 7
( . 5 - 4 . 6 ) ( 0 . 5 - 5 . 1 )
0 . 0 3 - 0 . 0 4 9 2 4 7 3 . 4 3 . 9
( 1 . 0 4 - 1 1 . 1 ) ( 1 . 2 - 1 3 . 4 )
0 . 0 5 - 0 . 1 9 9 1 3 0 5 2 4 . 7 5 . 5
( 1 . 9 - 1 1 . 4 ) ( 2 . 2 - 1 3 . 5 )
0 . 2 0 - 0 . 4 0 1 2 7 7 7 7 . 1 9 . 0
Cad. Saúd e Púb lic a, Rio d e Jane iro , 14(Sup. 3):193-198, 1998
( 1 . 6 - 7 . 4 )fo r st ra t a 1 t o 5, re s p e c t i ve l y. Bo th ser ie s p sere s e n t t h e sa m e t yp e o f sere la t ion sh ip b e -t we en exp osu re an d can ce r risk, a n d -t h e y we re t h us com b in ed fo r m o st of th e a n a lysis.
Skin le s io n s re la t e d t o ar se n ic ( Ta b le 3) we re m o re fre q u e n t a m o n g c as e s (34%) t h a n a m on g co n t ro ls (8%), wit h a lin e ar t re n d fro m n o lesion s to skin can ce r. We d id n o t con d u ct a va lid it y st u d y o f t h e n u rs e s’ d ia gn o s e s o r t h e p oten t ial b ias, given th at th ey we re n o t b lin d ed t o t he su b je ct s’ co n d it ion s.
Ta b le 4 p re s e n t s st u d y gro u p s cla ssifie d a s e ve r o r n e ve r sm o ke d . Od d s ra t io s o f As e xp o -s u r e a re p re -s e n t e d -se p a ra t e ly fo r t h e t wo g ro u p s. T h e re is a sligh t ly h igh er OR am on g th e s m o k e r s.
Ave ra ge n u m b e r o f p a cks o f ciga re t t e s sm o ked p e r ye a r by ca ses a n d co n tro ls sh owe d a cle ar d o se-re sp o n se re l a t i o n s h i p , wit h a n OR o f 1,1.8, 4.0, 5.4, a n d 14 fo r t h e st ra t a : 0; 1-90; 91-180; 181-400; a n d >400 p a cks o f ciga re t t e s / ye a r, re s p e c t i ve l y. Male s a n d fem a le s sh owe d a sim ila r cu rve, b u t th ere we re n o fem a le s in t h e h igh e st exp o su re gro u p
D i s c u s s i o n
Mo s t o f t h e a ss o cia t ion b e t we e n a r se n ic an d ca n cer risk in Ch ile h as b ee n b a se d on eco logi-ca l d at a sh ow in g a co rre la t io n b et we e n e xc e s s ris k o f s o m e ca n c e rs a n d h igh le ve ls o f As in d rin kin g wate r (Fe r re ccio e t al., 1997). Ec o l o g ica l s t u d ie s h a ve t h e p o t e n t ia l fo r m a n y co n -fo un d ers su ch a s o th er risk fa ct ors, d iffere n t d i-agn os t ic c ri t e ria , an d h o sp it a liza t io n ra t e s, a m o n gst o th e rs.
Th is in d ivid u a l- b a se d st u d y in t e n d e d t o a d d re s s so m e o f t h e se lim it at io n s b y e stim a t -in g t h e e xp o su re le ve l fo r e a c h su b je c t b a se d o n p e rs o n a l h is t o ry a n d co n tr o llin g fo r a ll k n own con fo u n d ers.
Pre vio u s e vid e n ce of t h e a s so cia t io n b e -t we e n As an d in -t e rn a l can ce rs h ad b e e n q u e s-t io n e d b e ca u s e a ll s-t h e e vid e n ce wa s b a se d m a in ly o n Ta iwa n e s e d a t a , w h ich m igh t h a ve b e e n a h igh ly su sce p t ib le p o p u latio n (Bat e s et a l., 1992; Sm it h e t a l., 1992; Bro wn & Ch e n , 1995; Ch io u e t a l., 1995; Mu sh a k & Cro c e t t i , 1995). Th is st u d y co n firm s Ta iwa n e se fin d in gs in a ve ry d ifferen t con t ext. Th is is th e first st u d y of th is kin d in Ch ile an d sup p ort ed th e eco logi-ca l e vid e n c e a s we ll a s p re vio u s st u d ie s d o n e e l s e w h e re.
Am on g t h e lim it a t io n s o f t h is st u d y is t h e p o t e n t ia lly in c o m p le t e ca s e id e n t ifica t io n . In fa ct , so m e ca se s in h igh so cioe co n o m ic gro u p s m a y h a ve b e en m isse d . Wh e n m e m b e rs o f th is g ro u p d e ve lo p s e ve re h e a lt h c o n d it io n s like su s p e ct e d c a n c e r, t h e y s e e k m e d ica l c a re in th e Gre a te r Me t ro p olit a n Area. T h e re is n o re a -so n t o b elie ve th at t h is gro u p o f p o t e n t ia l c a se s w ill h a vse a d iffse rse n t se xp o s u rse ra t se t o a r se n ic t h an t h e ca se s fro m t h e ge n e ra l p o p u la tio n , sin ce eve ry h o u se h o ld ge t s t h e sam e wa
-Tab le 2
Life time arse nic le ve l in d rinking wate r fo r lung c ase s and e ach type o f c o ntro l. Ave rag e As 1930-19 94.
M ean As (mg/ L) C o n t rol A C o n t rol B Cases O R O R ( N : 1 6 7 ) ( N : 2 4 2 ) ( N : 1 5 1 ) C o n t rols A C o n t rols B
0 - 0 . 0 1 3 0 4 0 6 1 1
0 . 0 1 - 0 . 0 2 9 2 7 4 1 9 2 . 0 1 . 5
( 0 . 6 - 6 . 7 ) ( 0 . 5 - 4 . 7 )
0 . 0 3 - 0 . 0 4 9 7 1 7 7 5 . 7 3 . 1
( 1 . 4 - 2 3 . 5 ) ( 0 . 9 - 1 1 . 1 )
0 . 0 5 - 0 . 1 9 9 5 9 7 1 5 2 5 . 3 5 . 7
( 1 . 9 - 1 4 . 3 ) ( 2 . 1 - 1 4 . 7 )
0 . 2 0 - 0 . 4 0 4 4 8 3 7 7 1 1 . 7 7 . 4
( 4 . 3 - 3 2 . 0 ) ( 2 . 9 - 1 8 . 9 )
Tab le 3
Skin status amo ng stud y sub je c ts.
Skin St atus C o n t rols (%) Cases (%) O R (CI 95%)
No As le sio n 38 4 (92) 101 (6 6) 1
P i g m e n t a t i o n 26 (6) 33 (22) 4 . 8 ( 2 . 7 - 8 . 8 )
K e r a t o s i s 8 (2) 1 2 (8) 5 . 7 ( 2 . 1 - 1 5 . 8 )
C a n c e r 1 (0. 2) 5 (3.3) 1 9 . 0 ( 2 - 4 0 0 )
Cad. Saúde Púb lic a, Rio de Jane iro , 14(Sup . 3):193-198, 1998 te r in u rb an a re a s, re g a rd le ss o f so cio e co n o m
-ic st a t u s.
An o t h e r lim it a t io n re lat e s t o t h e e xp o su re id e n t ifica t io n . Alth ou gh a rsen ic e xp osu re d ata we re t h o ro u gh , t h e re we re so m e ye a rs wit h n o d a ta . Th is in co m p le te n ess cou ld le a d t o ove r – o r u n d e re s t im at io n o f e xp o s u re . Th e e xp o se d a re a s h a ve t h e m o st co m p le t e d a t a se r i e s, so flu c t u a t io n s in e xp o su re le ve ls a re we l l d o c u -m e n t ed . Th e -m a in d istortio n in esti-m at es cou ld a ffe ct t h e c o m p a riso n gro u p , i.e ., th e c o n t ro l g ro u p s. Sin ce As c a n a ffe ct a n y o rga n sys t e m , d isea sed p atie n t s m a y h a ve b e en m ore exp ose d t o a r se n ic t h a n t h e ge n e r a l p o p u la t io n , t h u s p rod u cin g a n u n d e res tim a tio n o f t h e rea l r i s k .
T h u s, ou r re su lt s m ay b e a ve ry con se rva t i ve es-tim a tio n of th e real risk of As in d rin kin g wa ter.
T h e re h a s a lso b e e n a d e b a t e a b o u t t h e f o r m of t h e d o se -re sp on se relat ion b etwe en ar-se n ic a n d ca n ce r risk (He rtz -Piccio t o & Sm i t h , 1993; Wu e t a l., 1989). Th is st u d y su p p o r t s t h e l i n e a rit y a ssu m p t ion fo r t h is re l a t i o n s h i p
Th e safe t y le ve l for a rse n ic in d rin kin g wa -t e r e s-t a b lish e d by -th e U S EPA (U SA EPA, 1988) a n d b y t h e Ch ile a n Mi n i s t r y o f He a lt h is 0.05 m g/ L, b u t t h e c u rre n t WH O re c o m m e n d a t i o n is m u ch lowe r (0.01 m g/ L). This stu d y su p p o rt s t h e as se rt io n t h a t As is a n e t io logic fa c t o r fo r i n t e r n al ca n ce rs an d th at th e cu rren t n o r m fo r As leve ls co u ld b e u n sa fe.
Tab le 4
Risk o f lung canc e r and e xp o sure to arse nic b y smo king status.
Lifet ime average N ever smoked Ever smoked As drinking wat er C o n t ro l s C a s e s O R C o n t ro l s C a s e O R
( m g / L ) 1 8 9 3 0 2 3 0 1 2 1
< 0.001 2 5 1 1 4 5 5 1
0 . 0 0 1 - 0 . 0 2 9 2 8 1 1 . 1 4 0 8 1 . 9
0 . 0 3 - 0 . 0 4 9 1 0 0 i n c 1 4 7 5 . 1
0 . 0 5 - 0 . 1 9 9 5 9 1 1 5 . 7 7 1 4 1 5 . 4
> 0.200 6 7 1 7 8 . 3 6 0 6 0 9 . 2
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