Cad . Saúd e Púb lic a, Rio de Jane iro , 14(Sup. 3):181-185, 1998
Familial aggregation of breast / ovarian
cancer: age of onset along subsequent
generat ions in Brazil
A g re g aç ão familiar d e c ânc e r d e mama
e o vário : id ad e d e manife staç ão
e m g e raç õ e s sub se q üe nte s no Brasil
1 De p a rt am en to de Ep i d e m i o l o g i a , Esco la N a cio n al d e Sa ú d e Pú bli ca , Fu n d ação Osw ald o Cru z . Ru a Leop ol d o Bu lh ões 1 480, R io d e Ja n e i ro, RJ 2 1 0 4 1 - 2 1 0 , Bra s i l . 2 In stitu t o Fe r n a n d e s Fi g u e i ra , Fu n d ação Osw ald o Cru z . Av. Ru i Barbo sa 71 6, Rio d e Ja n e i ro, R J 2 2 2 5 0 - 0 2 0 , Bra s i l .
k o i f m a n @ d c c 0 0 1 . c i c t . f i o c r u z . b r
Rosa li n a Jorge Koif m a n 1
Sergio Koif m a n 1
Ro b e rt o Jo sé d a Si l va Vi e i ra 2
Abstract An teced en t s of fa m ilia l a ggrega t ion o f brea st a n d ov aria n ca n cer a re ob served in on ly 5-8% of a ll b rea st ca n cer ca ses. Ne ve rt h e l e s s , t h is v a ria ble d isp lays on e of t h e h igh est ri sk ra t i o s a ssocia t ed t o brea st can cer o u t com e. Desp it e recen t id en t ifica t ion of gen et ic m u t a t ion s associat -ed w i t h fa m ilia l a ggrega t ion of t h ese t u m o rs, m ai n ly at BRCA1 a n d BRCA2 gen es, k n ow l-ed ge on t h e i n t e ra ct io n b et w een en v iron m en t a l a gen t s in t h ese f a m ilies rem a i n s q u it e u n clea r. In t h is p a p er w e a scert a i n e d t h e correla t i on a m on g a ges of t h e o n set o f b re a s t / ov a ri a n ca n ce r i n 260 Bra z i li a n fa m i li es w it h t h o se ca n cer a ggre g a t i o n . Fu rt h er w e est im a t ed t h e m ed i a n a ge of t h e on set of brea st ca n cer a m on g fou r gen era t i o n s . W e o bserved t h a t t h e h i gh er th e n u m b er of fam ily ca n cer cases, t h e h igh est is t h e correla ti on of a ges for t h e on set of brea st ca n cer. We a lso observe d a 810 yea r declin e in t h e m ean ageofo n set of bre a s t / ov aria n can cer fro m on e gen era t io n t o a n -ot h er in t h e st u d ied f a m i lies. If t h ese resu lt s cou ld b e con fi rm ed elsew h e re , w e b eliev e t h a t t h e h yp o t h esi s of in t era ct i on b et w een en v iro n m en t a l ri sk s f a ct o rs i n f a m i li es i n d eed sh ow i n g b re a s t / ov aria n can cer a ggrega t ion is re i n f o rc e d .
Key words N e o p l a s m ; Bre a s t ; Ov a ry, Ova r i a n ; Ge n e t i c s
Resumo A p resen ça d e a n t eced en t es d e agrega çã o fa m ilia r d e cân cer d e m a m a e ov ário é obser-v a da em a p en as 5% a 8% d e t odos os ca sos d e câ n cer de m am a . Est a obser-va r i á obser-ve l , e n t re t a n t o, é u m a d a s qu e a p re sen t a m a io r ra z ã o d e ri sco s p a ra o d esfech o câ n cer d e m a m a . Ap esa r d a i d en t i f i-ca ção recen t e d e m u t a çõ es gen ét ii-ca s a ssoci ad as com a a gregaçã o fam ilia r dest es t u m ore s , s o b re-t u d o n os gen es BRCA1 e BRC A 2 , o co n h ecim en re-t o sob re a s i n re-t era çõ es en re-t re fa re-t ores a m bien re-t a i s e gen ét i co s n essa s f a m í lia s p erm a n ece re l a t i v a m en t e o bscu ro. N est e t ra b a l h o, d et e rm i n a m o s a c o r rela çã o d a s i d a d es d e i n í ci o d e câ n cer d e m a m a e ov á ri o e m 260 f a m í li a s co m a gru p a çã o d aq u eles t u m ore s . Po s t e r i o r m e n t e , foi est im a da a id a d e m éd ia d e in ício d estes t u m ores a o lo n go d e q u a t ro gera ç õ e s . Ob s e rv o u -se q u e q u a n t o m a i or o n ú m ero d e ca so s d e câ n ce r n a f a m í li a , m a i or o coeficien t e de correla ção en t re a s id ad es d e in ício d est es câ n cere s . Foi t am bém con sta t a -d o u m -d eclín io -de o it o a -d ez a n os n a i-d a -d e m é-d ia -d e in ício -d o câ n cer n essa s fa m ília s ao lon go -d e t rês gera ç õ e s . Os a u t ores acred it a m qu e, se esses resu lt a dos forem con firm a d os p or ou t ra s in ve st i g a ç õ e s , refo rça se a h ip ó st ese de u m a i n st era çã o en st re fa st o res a m bien st a is e ge n ést i co s n o d esen -ca d ea m en t o d os t u m ores d e m am a e ov á rio em fam ília s qu e já a p resen t a m u m a fort e a gre g a ç ã o d esses tu m o re s .
C ad. Saúde Púb lica , Rio de Jane iro , 14(Sup. 3):181-185, 1998
I n t ro d u c t i o n
Breast ca n ce r h a s b e e n a lea d in g ca use of ca n -c e r a m o n g w o m e n in d e ve lo p e d -c o u n t r i e s, s h o win g a n in cre as in g in c id e n c e a n d st a b le m o r t alit y d u rin g t h e la st d e ca d e s (Ga rfin ke l e t a l., 1994). Am o n g t h e kn o wn risk fa cto r s asso -c ia t e d t o t h a t d ise as e, fa m ilia l a ggre ga t io n o f fe m a le b re ast ca n ce r h a s b e en id e n t ified a s a n i m p o rt a n t co n d it io n yie ld in g t o in cre a se d r i s k o f d e ve lo p in g t h a t t u m o r. An t e ce d e n t s o f fir st d e g re e r e l a t i ve s a ffe ct e d wit h b re a s t ca n c e r ra n ge s fro m 8% to 30% am o n g ca se s with su ch h i s t o r y (An d erson & Bad zioch , 1985; Dawso n & Th om p so n , 1989; Ma rcu s e t a l., 1996). In d e e d , ris k r a t io s a s h igh a s 5 h a s b e e n m e n t io n e d a m o n g w o m e n wit h p re viou s c a se s o f b re a s t can cer a m o n g close re l a t i ve s, su ch a s a m o th er o r a sis t e r, a s co m p a re d w it h wo m e n w it h o u t fa m ily a n t e c e d e n t s o f t h a t n e o p la s m (Ke l s e y, 1993). Fo r in s t a n ce , if ju s t a wo m a n ’s m ot h e r h a s h ad b rea st ca n cer, h er re l a t i ve risk to d eve l-o p t h e sam e ca n c er is 1.8; if l-o n e siste r h a s h ad t h e d ise a se, t h e r isk is q u it e h igh e r, 2.5; m o re -o ve r, if b -o t h m -o t h e r a n d sis t e r h a d d e ve l -o p e d b re a st can cer, th e r isk ju m p s t o 5.6 (Bain et al., 1980). Th e re a so n s in vo l ve d in t h is p roce ss re -m a in e d q u it e u n cle a r u n t il t h e la st fe w ye a r s wh e n kn o wle d ge a b o u t t h e ge n e t ics o f b r e a s t c a n ce r e xp e r ie n c e d a re m a rkab le im p r ove -m e n t .
Fa m ilial b re a st ca n ce r is n ow kn own t o d e ve lo p in m u lt ip le fa m ily re l a t i ve s a m on g su b -s e q u e n t ge n e r a t i o n -s, ve r y o ft e n b ila t e r al, a n d at re l a t i vely you n g a ges. Up to n ow, som e gen e s we re id e n tifie d a s h a vin g a n im p o rt a n t ro le in fa m ilia l a ggre ga t io n o f b re a st c a n ce r. At fir st , t h e ge n e n a m e d BRCA1 (for b re as t c an ce r) lo -c a t e d in -c h ro m oso m e 17 h ad b e e n im p li-ca t e d in ca n ce r e xp re ssio n o f fa m ilie s d isp la yin g fe -m a le b re a s t a n d ova r ia n ca n ce r (Ha ll e t a l., 1990). Mo re th an eigh t y m u t a tion s in t h is ge n e we re d escrib ed , d esp it e th e fa ct t h at th e im p ort a n ce o f m os ort o f ort h e m re m a in s u n kn own . An -o t h e r ge n e in v-o l ve d in fa m ilial a ggre ga t i-o n -o f b rea st ca n cer is BRCA2 lo cat ed at ch ro m o s o m e 13, a n d m ain ly a sso c iat e d w it h ca se s o f m a le b re a s t c an ce r a n d o va ria n ca n c e r in t h e sa m e f a m i l i e s. Th e e xis t e n c e o f a t h ird ge n e , st ill u n id e n tified , yet n am e d BRCA3, was d iscu ssed t akin g in t o accou n t ob se rva tion of fam ily ca se s o f b re a s t a n d ova ria n c a n ce r wit h o u t s h ow i n g m u t a t io n s e it h e r on BRCA1 o r BRCA2. As a w h o l e , BRCA1 a n d BRCA2 (o r e ve n BRCA3 if f u rt h e r id e n t ifie d ) se e m s t o p la y t h e m o st im -p o r t a n t ro le in fa m ilia l a ggre gat io n of b re a s t a n d ova rian can cer cases, wh ile p 53 gen e s e e m s t o b e m o re in vo l ve d in t h e e xp re ss io n o f sp o
-ra d ic b re a st ca n cer ca ses (Elle d ge & Ma c Gu i re, 1994; O zb u n & Bu t e l, 1995). Ne ve rt h e l e s s, p 53 ge n e was a lso d e sc rib e d in L Fra u m e n i fa m i-lie s ( Malkin e t a l., 1990).
Th e m a n n er in w h ich ge n e t ic an d e n viro n -m e n t a l risk fa ct o rs a ct d u r in g c arc i n o g e n e s i s e it h e r o n fam ilia l a ggre gat io n a n d s p o r a d i c b re a s t ca n ce r re m a in s u n c le a r. T h e re f o r e, e f-f o rt s h ave b ee n m a d e t r yin g to im p rove u n d e rst an d in g o f t h e ir p o ss ib le in t e ra ct io n b y d e -s c rib in g p a t t e rn -s o f d i-se a -se -sp re a d in g a m o n g p o p u l a t i o n s. Early m en a rc h e, la t e m e n o p au se, d e clin in g p ar it y a n d co n su m p t io n o f o ra l co n -t ra c e p -t i ve s d u r in g a d o le sc e n c e b e fo re a fu ll-t e rm p re g n a n c y, we re a lso p o in ll-t ed o u ll-t as va riab les p o ssib ly a sso ciat ed w it h b rea st ca n cer re -lat ed to a p a tt ern o f h igh e xp osu re to e st ro g e n s d u rin g t h e re p ro d u c t i ve ye a rs (Ke l s e y, 1993; Ne wc o m b e t a l., 1996). Ne ve rt h e l e s s, t h e se va r ia b le s s e e m s t o a c t d iffe r e n t ly if ca s e s a re s p o ra d ic o r fam ily aggre ga t e d (Co ld it z e t a l., 1 9 9 6 ) .
Am o n g va r iab le s as so cia t e d t o b re ast c a n -c e r, a ge is p erh ap s o n e o f th e b e st d o-cu m e n ted in lit era t u re. Bre ast ca n cer in d iffe re n t p o p u la -t io n s sh ow q u i-t e s im ila r d is-t r ib u -t io n s b y a ge , wit h s h a r p in c re a se s o n in cid e n ce ra t e s b e t wee n 25 a n d 45 yr. o ld , followe d b y a slower in c re asin g sp e e d o n in cid e n ce a ft e r th a t a ge. In -d e e-d , t h is ob ser va tion h as b e en p oin t e-d ou t as a st ro n g in d ica t o r of h orm on a l in vo l ve m en t in b re as t c an ce r d e ve lo p m e n t. T h e re f o re, b re a s t ca n ce r is m a in ly a p o st -m e n o p a u sa l d is e a se , a ffe c tin g a r o u n d 4% o f wo m e n b e lo w 35 yr s. o ld (Ch u n g e t a l., 1996) an d 7% b e low 40 yr s. o ld ( Wi n c h e s t e r, 1996). Th e m a jo rit y o f c a se s a re d ia gn o sed b etwe en 45 an d 55 yrs. o ld in t h e U SA, a n d o n ly 20% a m o n g wo m e n 75 yr s. o r o ld e r (Bu sc h e t al., 1996). On e o f t h e m o s t in -t e re s-t in g fin d in gs re c e n -t ly m e n -t io n e d in -t h e l i t e ra t u re ab o u t a ge d ist rib u tio n o f b rea st ca n -ce r is t h e d e clin e in t h e a ge o f o n se t a m o n g b re a st c a n ce r c a s e s o b s e r ve d d u r in g t h e la s t d e c a d e s.
D i f f e re n t st u d ie s h a ve sh own t h a t age o f o n s e t a m o n g fa m ilie s wit h se ve ra l c as e s o f b re ast can cer u su ally sta rt a t you n ge r a ge s th a n o b s e rve d am o n g s p o ra d ic ca se s in t h e ge n e ra l p o p u la t io n (Do t t o, 1985). Ne ve rt h e l e s s, t h e m a n n e r in wh ich c a se s fro m fa m ilie s wit h a n -te ce d e n t s of b rea st a n d ova ria n ca n ce r b e h a vio r h as b e e n p oo r ly d o cu m e n t e d in t h e lit e ra -t u re w i-th re g a rd -to age d is-t rib u -tion a m on g su c-c e s s i ve gen era t i o n s.
Cad. Saúde Púb lic a, Rio d e Jane iro , 14(Sup. 3):181-185, 1998 Im plicat io n s o f th e o b ser ved tren d s will b e fu
r-t h e r co m m e n r-t e d o n w ir-t h co n sid e ra r-t io n r-t o a va ila b le kn owle d ge in t h e lite ra t u re.
M e t h o d s
Sin ce 1994, t h e Bra zilia n Na t io n a l DN A Ba n k Pro g r a m (BN DBP) h a s b e e n ga t h e r in g b lo o d sam p les a n d ep id em io lo gica l in fo rm at ion fro m fa m ilie s sh o win g a ggre ga t io n o f b re a st a n d ova ria n ca n cer in d iffe re n t cit ie s. At first Rio d e Ja n e i ro, Sã o Pa u lo a n d Po rt o Ale gre we re in -clu d e d , wit h t h is list in cre a sin g wit h t im e. Blo o d sa m p le s h a ve b e e n u se d t o id e n t ify ge -n et ic m u ta tio-n s, wh ich will b e fu rth er li-n ked to e p id em io lo gica l d at a a im in g t o an alyze p o ssi-b le p at t e r n s o f t h eir d ist rissi-b u t ion a m o n g t h e s e f a m i l i e s. In t h is p a pe r, we will p resen t e p id e m i-o li-o gica l in fi-o rm a t ii-on i-o n t h e d ist rib u t ii-on i-of a ge fo r t h e o n se t a m o n g c a se s o f b r e a s t / ova ri a n ca n ce r id e n t ifie d a m o n g fa m ilie s wit h 3 o r m o re b re a s t / o va r ia n ca n c e r cas e s in t h e t h re e a f o rem e n t io n e d cit ie s.
At firs t , Pe a r s o n’s co rre la t io n co e fficie n t s b e t wee n a ges o f on set o f b re a s t / ova ria n ca n cer a m o n g e n ro lled wom en in BNDBP was carri e d o u t . Fu rt h e rm o re , d ist r ib u t io n o n t h e a ge s o f t h e o n s e t o f b re a s t / ova ria n ca n c e r w a s a s ce r -t a in e d a m o n g su b s e q u e n -t ge n e r a -t io n s in -t h e sam e fa m ilies. Th e se age s we re d e te rm in ed to -w a rd s t h e m ed ian a ge of o n se t in ea ch ge n e ra-tion for e a ch fa m ily, a s a m e a su re t o gu ara n t e e t h e sa m e p ro b a b ilit y fo r a ll fa m ilie s t o b e re p -re sen t e d , -re g a rd le ss o f t h e n u m b e r o f a ffe ct e d wo m e n in each fa m ily.
Result s and discussion
Am o n g e n ro lle d fa m ilie s in BND BP, 260 h a ve t w o o r m o re c a s e s o f b r e a s t / o va r ia n c a n c e r in Rio d e Ja n e i ro a n d Sã o Pa u l o , 64 o f t h e m wit h 4 o r m o re ca se s. Me d ian age a t d ia gn o sis a m o n g e n r olle d ca se s w it h 4 o r m o re fa m ily
ca s e s wa s 52 yr. a n d 48 yr. a m on g t h e ir c lo se re l a t i ve s.
As se en in Ta b le 1, a h igh co rrela tio n o f a ge a t t h e o n s e t b e t w e e n c lo s e re l a t i ve s o f c a n -c e ro u s e n ro lle d wo m e n wa s o b se rve d : r = 0.95 (0.81- 0.99), F1 ; 9= 81.2, p <0.005. Co r re lat io n of
a ge a t t h e o n se t a m o n g clo se re l a t i ve s o f n o n -c a n -c e r o u s e n r o lle d w o m e n w it h m u lt ip le fa m ily ca s e s (4 o r m o re ) w a s a ls o h igh , r = 0.79 (0.59-0.80), F1 ; 8 2= 84.0, p <0.005. Am o n g
n on c an ce r o u s e n ro lle d wo m e n wit h 3 o r le s s fa m ily c a se s, t h e c o rre la t io n c o e fficie n t w a s m o d e ra t e , r = 0.43 (0.33-0.53), F1 ; 2 5 7 = 59.3,
p < 0 . 0 0 5 .
Th e se re s u lt s su gge s t a st ro n g co rre l a t i o n b e t we e n a ge s a t o n se t o f b re a st an d o va ri a n ca n cer a m o n g re l a t i ve s from fa m ilies with p ast fa m ily a n t ece d en t s of th e se t um o r site s. Mo re-ove r, t h e h igh er th e n u m b er of fam ily cases, th e h igh e r corre la tio n w as o b se rve d b e t we e n age s o f b re a s t a n d ova r ia n ca n ce r o n se t. Ne ve rt h e -l e s s, t h ese re su -lts a re n o t in fo rm a t i ve o n d ire c-t io n a lic-t y o r c-t im in g a b o u c-t a ge s o f o n se c-t , a n d t h e y ju s t in d ic a t e s im ila r it y b e t w e e n t h e s e a ge s a m o n g a ll s t u d ie d fa m ilie s. In o t h e r w o rd s , t h e y ju st re ve al an im p o r ta n t close n e ss o r sim ilarity b et we en a ge gro u p s in wh ich cas-e s wcas-e rcas-e d ia gn o s cas-e d a m on g fa m ilicas-e s w it h p as t a n t e ce d e n t s o f b re a s t / ova r ian ca n cer.
To a n a lyze tim e t re n d s o n t h e a ge o f o n s e t o f b re a s t / ova ria n c an ce r, Ta b le 2 is m o re u se -fu l: w h e n d ist rib u t io n o f age s o f t h e o n se t o f b re a st a n d ova r ia n ca n ce r wa s c a rr ie d o u t a lo n g s u b s e q u e n t ge n e ra t i o n s , a d e c lin e o n t h e m e a n a ge of o n se t wa s o b se rved : 53.4 yr. in t h e first gen era tio n o f affect ed wo m en , 43.3 yr. in t h e se co n d , 34.6 yr. in t h e t h ird an d 30.5 yr. in t h e fo u rt h (F = 30.85; p <0.00001). Th e se re -s u lt -s – o b t a in e d t ow a rd -s -se ve ra l in t ra - f a m i l y c o m p a r iso n s a lo n g su b se q u e n t ge n e ra t io n s o f clo s e re l a t i ve s –, su gge st a m a rke d d e clin e a m o n g a ge s in wh ich t h e se t u m or s we re d ia g-n o se d , i.e ., a 8-10 ye a r s d e clig-n e b e t we e g-n t wo su b se q u e n t ge n e ra t io n s c on sid e r in g t h e firs t t h ree on e s.
Tab le 1
Distrib utio n o f c ase s o f b re ast/ o varian canc e r am o ng e nro lle d familie s, Brazilian Natio nal DN A Bank Pro g r a m .
r 95% C.I. F p value
Clo se re lative s o f affe cte d wo me n 0 . 9 5 0 . 8 1 - 0 . 9 9 8 1 . 2 < 0.005 C lo se re lative s o f no n-affe c te d 0 . 7 9 0 . 5 9 - 0 . 8 0 8 4 . 0 < 0.005 4 o r mo re family c ase s
Cad. Saúde Púb lica , Rio de Jane iro , 14(Sup . 3):181-185, 1998
Th e se r e su lt s sh o u ld b e in t e rp re t e d c a u -t i o u s l y, b e ca u s e -t h e y m a y b e b ia se d in -t h e s e n s e t h a t wo m e n in t h e firs t ge n e ra t io n h a d e x p e rien ced a h igh er life sp an th a n t ho se in th e t h i rd o r t h e fo u rt h ge n e ra t ion , wh o st ill are in t h e ir 30’s o r 40’s. T h e re f o re, a s t h e ir fo llo w u p goe s on , ca ses a t old e r a ges will ce rta in ly b e d i-a gn o se d , in cre i-a sin g t h e m e i-a n i-age o f o n se t in t h e re s p e c t i ve t h ird an d fo u rt h fa m ily ge n e ra -t io n . Mo re ove r, m am o gra p h y acc e ss m a y a ls o a l l ow b re a st c a n c e r d e te ct io n a t e a rlie r a ge s , ch a n gin g th e m e an a geo fo n set o f b re ast ca n -c e r a m o n g d iffe re n t ge n e ra t i o n s. He n -c e f o rt h , we b elieve t h at a co n tin u ou s follow u p of th ese wom e n sh ou ld yield to close r m e an a ges at th e o n se t o f b re a s t / o va r ia n c an ce r t h an t h e t im e i n t e r va l n ow ob se r ve d (8-10 ye a rs b e t w e e n su b se q u e n t gen era tion s). Ne ve rt h e l e s s, we also co n sid e r t h e se in t e r va ls so la rg e , t h a t it se e m s q u it e im p ro b a b le t h a t life lo n g co rre c t io n o f a ge s a t t h e on se t, b rou gh t b y a co n t in u o u s fo l-l ow u p, co u l-ld e l-lim in a te t h e cu rren t d iffere n c e s o b s e rve d a m on g wo m e n in su b se q u e n t ge n e r-a t i o n s.
Co n s e q u e n t l y, we b e lie ve t h at p re se n t re -su lts m a y in d e ed p oin t ou t a tr u e t ren d t ow a rd s
a d eclin e in th e age of t h e o n set of b re a s t / ova r-ia n ca n c e r d r-ia gn o s e d a m o n g wo m e n fro m fa m ilie s wit h a st r on g p a t t e r n o f t h e se t u m o rs a g g regation . T h e re f o re, a com p re h e n s i ve a n a l yse s ta kin g in to accou n t th e role o f en viro n m e n -t a l ris k fac -t o rs -t o b re a s -t a n d ova ria n ca n ce r a m o n g fa m ilie s sh owin g t h is t u m or a ggre g a -tio n p a t t ern in co n t e m p o ra r y so cie t ie s sh o u ld b e e xp lored . Un f o rt u n a t e l y, t h e m a jo rity o f ep id em io logical stu id ie s an alyzin g fa m ily a ggre g a tion of b rea st can ce r h ave st ill b e en ju st ori e n t e d t ow a rd s t h e im p o rt a n t ge n e t ic a sp e ct s in -vo l ved in t h is p ro c e s s, a n d n ot con sid e rin g t h e p ro b a b le r ole o f e n viro n m e n t a l ris k fac t o rs in th e ir e xp re ssio n .
C o n c l u s i o n s
A sa m p le o f Bra zilia n fa m ilie s sh o win g a p a t -t e rn of b re a s-t a n d ova r ia n ca n ce r a ggre g a -t i o n wa s st u d ie d . A s t a t is t ic a lly s ign ifica n t 8 t o 10 y r. d e c lin e o n t h e m e a n a ge o f t h e o n se t o f b re a s t / o va ria n ca n ce r a m on g t h e ir clo se re l a -t i ve s w a s ob se r ve d a lo n g -t h r e e s u b se q u e n -t g e n e ra t i o n s.
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Tab le 2
Ag e o f o nse t o f b re ast/ o varian canc e r alo ng family g e ne ratio ns*, se le c te d b razilian c itie s**.
G e n e r a t i o n F a m i l i e s M ean age S t a n d a rd erro r 1st q uart i l e M e d i a n 3 rd q uart i l e ( n ) ( y e a r s ) ( y e a r s ) ( y e a r s ) ( y e a r s ) ( y e a r s )
F i r s t 1 0 0 5 3 . 4 1 . 1 4 6 . 0 5 0 . 0 6 0 . 0 S e c o n d 1 0 0 4 3 . 3 0 . 9 3 8 . 0 4 3 . 0 5 0 . 0 T h i rd 2 5 3 4 . 6 1 . 8 2 7 . 0 3 3 . 0 3 8 . 0 F o u rt h 2 3 0 . 5 * * * 1 . 5 2 9 . 0 3 0 . 5 3 2 . 0
* At le ast two g e ne ratio ns o f affe c te d wo me n and 3 o r mo re case s o f b re ast/ o varian c ance r. ** Rio d e Jane iro , São Paulo and Po rto Ale g re .
Cad . Saúd e Púb lic a, Rio de Jane iro , 14(Sup. 3):181-185, 1998
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