Full Te ms & Condi ions o access and use can be ound a
h p://www. and online.com/ac ion/jou nalIn o ma ion?jou nalCode=ionc20
Download by: [Tampe e Uni e si y] Da e: 11 June 2017, A : 22:06
Ac a Oncologica
ISSN: 0284-186X (P in ) 1651-226X (Online) Jou nal homepage: h p://www. and online.com/loi/ionc20
Challenges in e alua ion o sc eening o gas ic
cance among men based on non andomized
design
Ilkka Vohlonen, Ma i Hä könen, Nea Malila, Ee o Pukkala, Pen i Sipponen,
Veli Kois inen & Ma i Hakama
To ci e his a icle: Ilkka Vohlonen, Ma i Hä könen, Nea Malila, Ee o Pukkala, Pen i Sipponen,
Veli Kois inen & Ma i Hakama (2017) Challenges in e alua ion o sc eening o gas ic
cance among men based on non andomized design , Ac a Oncologica, 56:7, 917-922, DOI:
10.1080/0284186X.2016.1278304
To link o his a icle: h p://dx.doi.o g/10.1080/0284186X.2016.1278304
© 2017 The Au ho (s). Published by In o ma
UK Limi ed, ading as Taylo & F ancis
G oup
Published online: 23 Feb 2017.
Submi you a icle o his jou nal
A icle iews: 118
View ela ed a icles
View C ossma k da a
ORIGINAL ARTICLE
Challenges in e alua ion o sc eening o gas ic cance among men based on
non andomized design
Ilkka Vohlonen
a
, Ma i H€
a k€
onen
b
, Nea Malila
c,d
, Ee o Pukkala
e,
, Pen i Sipponen
g
, Veli Kois inen
h
and
Ma i Hakama
i
a
Depa men o Public Heal h, Heal h Policy, Uni e si y o Eas e n Finland, Kuopio, Finland;
b
Depa men o Clinical Chemis y, Clinical
Chemis y, Uni e si y o Helsinki, Helsinki, Finland;
c
Cance Epidemiology, Finnish Cance Regis y, Helsinki, Finland;
d
School o Heal h
Sciences, Uni e si y o Tampe e, Tampe e, Finland;
e
Epidemiology, Finnish Cance Regis y, Helsinki, Finland;
School o Heal h Sciences,
Uni e si y o Tampe e, Tampe e, Finland;
g
Depa men o Pa hology, Pa olab Oy, Espoo, Finland;
h
Depa men o Bios a is ics, Finnish
Consul ing G oup, Helsinki, Finland;
i
Depa men o Epidemiology, Finnish Cance Regis y, Helsinki, Finland
ABSTRACT
Backg ound: Objec i e was o quan i y biases in sc eening o gas ic cance when compa ing a end-
e s o nona ende s using se um pepsinogen I (SPGI) le el as p ima y es .
Me hods: In mid 1990s, all men aged 51–65 yea s om wo Finnish ci ies we e in i ed o SPGI sc een-
ing. Mo ali y and p ema u e mo ali y in a ende s we e compa ed o nona ende s. E icacy o sc een-
ing was s udied by 15 yea s’ ollow-up o s anda dized mo ali y a io (SMR) and po en ial yea s o li e
los (PYLL) due o gas ic cance . Bias due o selec i e a endance was quan i ied using co ec i e coe -
icien s based on o al cance incidence and mo ali y, and gas ic cance -speci ic incidence and mo al-
i y o o al popula ion and nona ende s.
Resul s: In 1994–1996, men aged 51–65 yea s (16,872) we e in i ed o SPGI assay and 12,175 men
(72%) a ended. SPGI was 25 mic og/l o less in 610 (5%) men, indica ing se e e a ophic gas i is (AG).
Pos -sc eening gas oscopy was pe o med o 435 men wi h low SPGI. O hese, 168 men we e e e ed
o ea men due o abno mal ocal lesions. A ibu able p opo ions in educ ions o SMR and PYLL
om gas ic cance due o sc eening we e 59% and 67%. A e co ec ing o selec i e pa icipa ion,
a ibu able p opo ions we e educed o 23% and 39%.
Conclusions: Bioma ke sc eening by low SPGI among middle-aged men ollowed by uppe gas o-
in es inal endoscopy dec eased long- e m and p ema u e mo ali y due o gas ic cance . Howe e , in
spi e o me hodological co ec ions done, he esul s do no jus i y any i m conclusions o ecommend
gene al sc eening p og ams. Randomized ials a e wa an ed o his pu pose.
Abb e ia ions: SPGI: se um pepsinogen I; AG: a ophic gas i is; SMR: s anda dized mo ali y a io; SIR:
s anda dized incidence a io; PYLL: po en ial yea s o li e los
ARTICLE HISTORY
Recei ed 9 Oc obe 2016
Accep ed 28 Decembe 2016
In oduc ion
In Finland, a popula ion-based sample o middle-aged men
om wo ci ies was in i ed in 1994–1996, o in es iga e
whe he a se um pepsinogen I (SPGI) sc eening, ollowed by
uppe gas oin es inal (GI) endoscopy in hose wi h low SPGI,
can be applied as a public heal h p og am. I was known
ha SPGI le els o 25 mic og/l o less indica e ad anced
(mode a e o se e e) a ophic gas i is (AG) in he gas ic co -
pus and undus wi h high eliabili y [1–4]. Howe e , he indi-
ca o s o s uc u e, p ocess, and ou come ela ed o
sc eening we e comple ely unknown.
The objec i e o his s udy was o ind ou whe he he
ecen labo a o y e idence o he e iological ole o SPGI was
su icien o s a sc eening and o quan i y challenges due
o bias in he e alua i e design. The sc eening was based on
pe sonal in i a ion o he a ge popula ion bu i did no
con ain any con ols. We s udied gas ic cance mo ali y by
compa ing he a ende s in sc eening wi h he nona ende s
o e mo e han 15 yea s ( om 1994 o 2011) a e sc eening
in 1994–1996. Since he design did no allow o a non-
biased assessmen o e icacy, s a is ical co ec ions we e pe -
o med o adjus o he e ec s o selec i e pa icipa ion.
Ma e ial and me hods
S udy popula ion and s udy coho s
All 16,872 men bo n in 1929–1943 and li ing in 1994–1996
in wo Finnish ci ies (Ko ka and Van aa) we e iden i ied by
popula ion egis y, and we e in i ed o gi e a blood sample
(se um) o he SPGI es : hal o hem in au umn 1994 and
he emainde in au umn 1996 (Table 1). Al oge he , 12,175
CONTACT Ilkka Vohlonen [email p o ec ed] Depa men o Public Heal h, Uni e si y o Eas e n Finland, B.O.X. 1627, 70100 Kuopio, Finland
Depa men o Bios a is ics, Finnish Consul ing G oup, Helsinki, Finland.
ß2017 The Au ho (s). Published by In o ma UK Limi ed, ading as Taylo & F ancis G oup
This is an Open Access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion-NonComme cial-NoDe i a i es License (h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/),
which pe mi s non-comme cial e-use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed, and is no al e ed, ans o med, o buil upon in
any way.
ACTA ONCOLOGICA, 2017
VOL. 56, NO. 7, 917–922
h p://dx.doi.o g/10.1080/0284186X.2016.1278304
men (72%) a ended he SPGI sc eening and 4697 did no .
They o m he a ende s (sc eened) and nona ende s (no
sc eened) in he p esen in es iga ion, espec i ely (Figu e 1).
Blood sampling and SPGI es
The men we e in i ed by mail o isi municipal heal h cen-
e s o blood sampling d awn by expe ienced labo a o y
nu ses. Fas ing se a we e collec ed in ap o inin (T asylol,
Baye Ge many, 200 KIE/ml) con aining Venojec ubes and
s o ed a –70 C un il analyzed. SPGI was analyzed using
he speci ic ELISA es s p o ided by Biohi Oyj, Helsinki,
Finland. The assay has been calib a ed o co espond o
esul s ob ained by adioimmunoassay (RIA) used by Samlo
in 1982 using 238 se um samples wi h se um pepsinogen
concen a ions be ween 1.5 and 120 mic og/L. The clinical
sensi i i y and speci ici y o ad anced AG a e 92% and
90% o he es , espec i ely, acco ding o he man-
u ac u e ’s ki ins uc ions o use. The sc eening was
app o ed by he E hics Commi ee o he Uni e si y
Hospi al o Kuopio in 1994.
Low SPGI le els (25 mic og/l o lowe ), indica ing he p es-
ence o ad anced (mode a e o se e e) AG in gas ic co pus
and undus, we e ound in 610 men (5% o he sc eened
men). Men wi h low SPGI le els we e con ac ed by elephone
and in i ed o gas oscopy unless hey had medical
con aindica ions.
Sc eening endoscopy in 1994–1996
A diagnos ic uppe GI endoscopy (sc eening gas oscopy)
was pe o med in 435 SPGI- es posi i e men; i.e., 71% o he
men wi h a low SPGI (Figu e 1). All hese endoscopies we e
pe o med by one expe ienced clinician. In endoscopy, biop-
sies om he s omach we e collec ed: wo om he an um
and wo om he co pus, acco ding o he guidelines o he
Sydney Sys em. Specimens o his opa hology we e also
aken om all ocal abno mali ies (e.g., e osions, ulce s, nod-
ules, polyps, masses, unusual colo spo s, e c.) seen by an
endoscopis in he s omach mucosa. In all, 168 men (1.4% o
all men in he sc eened coho ) we e e e ed o u he clin-
ical ea men o su eillance. O hese, 56 men had ocal
gas ic lesions wi h abno mal and a ypical mo phology in
biopsy pa hology, and all hese we e conside ed po en ially
cance ous o p ecance ous lesions (Figu e 1).
Follow-up and collec ion o mo ali y da a in 1994–2011
Long- e m ollow-up o all men in i ed o sc eening in
1994–1996 was un o cance incidence, dea hs, o emig a-
ion. These men o med he a ende s (sc eened) and nona -
ende s (nonsc eened) coho s as explained abo e. The
ollow-up s a ed he mon h a e s a o sc eening (on 1
Decembe 1994 o he hal o he men and on 1 No embe
Figu e 1. Design o he easibili y s udy on sc eening o gas ic cance in middle-aged men in wo Finnish ci ies in 1994–1996 using a bioma ke .
Table 1. Numbe and pe cen age o men, numbe o accumula ed pe son
yea s, and mean ime pe pe son in ollow-up in 1994–2011 by sc eening
s a us.
Men Pe son yea s
Sc eening s a us Numbe Pe cen Numbe Mean/pe son
Non-sc eened 4697 27.8 54,955 11.7
Sc eened 12,175 72.2 166,798 13.7
To al in i ed 16,872 100.0 221,023 13.1
918 I. VOHLONEN ET AL.
1996 o he o he hal ) and ended a dea h, emig a ion o
on 31 Decembe 2011 (Table 1). In o ma ion on gas ic can-
ce cases and dea hs in he coho s was ecei ed om he
Finnish Cance Regis y (FCR) and da a on emig a ion and
da e o dea h was om he popula ion egis e . The cause o
dea h in o ma ion o igina es om S a is ics Finland [5]. The
indi iduals in he s udy we e linked o egis e s using he
na ional pe sonal iden i y code o all Finnish esiden s.
Due o manda o y epo ing o all cance diagnoses in
Finland, he FCR has a good na ional co e age o o e 99%
o solid cance cases in Finland [6–8]. The egis y includes
da a o all gas ic cance cases ( opog aphy code C16 in ICD-
O-3) bu i does no include da a o cases classi ied as nonin-
asi e p emalignan lesions (dysplasia o in amucosal neo-
plasia). The cance in o ma ion used in his s udy included
he da e o diagnosis, opog aphy, mo phology, and da a
indica ing whe he he cance pa ien died om he cance
in ques ion o om any o he cause.
S a is ical me hods
The s anda dized mo ali y a ios (SMRs) and po en ial yea s
o li e los (PYLL) we e calcula ed o gas ic cance and o
all cance s combined (cance a any si e) [6,9] o a ende s
and nona ende s sepa a ely. In o de o calcula e he SMR,
he obse ed numbe s o dea h we e compa ed wi h he
expec ed numbe s among he a ende s and nona ende s.
The expec ed numbe s o each age g oup (5-yea age ca e-
go ies) and 4-yea calenda pe iod we e es ima ed by mul i-
plying he numbe o pe son yea s in he ca ego y
accumula ed among he a ende s and he nona ende s
coho s wi h he espec i e mo ali y a e in he o al male
popula ion in Finland. The 95% con idence in e als o
SMRs we e es ima ed assuming a Poisson dis ibu ion o
he numbe s o obse ed dea hs. S anda dized Incidence
Ra ios (SIRs) we e calcula ed acco ding o he same p inci-
ples as SMRs.
PYLL is an indica o o p ema u e mo ali y. I ep esen s
he o al numbe o li e yea s los (no li ed) by an indi idual
who was no assumed o die by a gi en age. The PYLL- alue
was calcula ed o each dead pe son as he di e ence
be ween he obse ed da e o dea h and he expec ed
leng h o li e. In he calcula ion o PYLL- alues, he expec ed
leng h o li e was se a he Finnish a e age s anda d (80
yea s). Those men who died a e hei 80-yea -old bi hday
did no con ibu e o he PYLL alue in any way. PYLL- alues
we e classi ied acco ding o he cause o dea h (s omach
cance o all cance s) and epo ed pe 1000 pe sons and pe
dea h among he sc eened and he non-sc eened.
S a is ical analyses
Due o selec i e a endance, he e ec o sc eening, i.e., e i-
cacy, was measu ed by wo ypes o a ibu able p opo ions
in educ ions o SMR and PYLL, he c ude a es and he co -
ec ed a es. In analyses o he a ibu able p opo ions in
educ ions o SMR and PYLL, he di e ences in he geo-
g aphic (e.g., supply and use o heal h se ices), social (e.g.,
demog aphic and e iological), and heal h (e.g., ea lie diagno-
ses) cha ac e is ics o he men be ween he wo coho s
we e co ec ed o , since he po en ial sel -selec ion co e-
la es wi h he p obabili y o dea h om gas ic cance . The
egional di e ences (heal h ca e supply) and he gene al isks
o any cance we e co ec ed o by aking in o accoun he
s anda dized incidence a ios and SMRs o all cance s o he
o al popula ion and o he nona ende s, as desc ibed
below.
In o de o adjus o sel -selec ion, we deno e:
M¼SMR o PYLL due o gas ic cance ,
I¼SIR o gas ic cance ,
a¼ hose sc eened,
an¼ hose no sc eened,
m¼SMR o PYLL due o all cance s,
i¼SIR o all cance s,
E1 ¼c ude e ec (a ibu able p opo ion),
E2 ¼e ec wi h co ec ion o selec ion and con ounding
ac o s (co ec ed a ibu able p opo ion).
The c ude es ima e o he e ec (E1) was es ima ed as:
E1 ¼1–(M
an
/M
n
).
The co ec ed es ima e o he e ec (E2) was es ima ed as:
E2 ¼1–(I
an
/I
a
)(M
an
/M
n
) (ma
an
/m
a
)(i
an
/i
n
).
Selec ion bias was co ec ed by he ela i e isk o back-
g ound incidence o gas ic cance in sc eened and non-
sc eened coho s (I
an
/I
a
). Fu he mo e, hose a ending
sc eening may ha e a be e gene al heal h and a mo e
a o able p ognosis han hose no a ending. We assumed
ha hese biases a e seen in he su i al and in he a io o
cance mo ali y o cance incidence (m/i) in he coho s, jus-
i ying he co ec ion ac o (m
an
i
a
)/(m
a
i
an
). The same o -
mulae we e used o co ec ing he di e ences in educ ions
o PYLL alues due o s omach cance be ween he a ende s
and nona ende s coho s by adjus ing o PYLL alues o
all cance s.
The mo ali y analyses o gas ic and all cance s we e i s
pe o med wi h e ined SMRs, i.e., excluding dea hs om gas-
ic cance diagnosed be o e he beginning o he ollow-up.
The e we e only ou such dea hs in he p esen se ies. The
e ined and he c ude SMR a es o all gas ic cance dea hs
u ned ou o be simila independen ly o ime o he diag-
nosis. Only he c ude SMRs and PYLL alues we e p esen ed
including all gas ic cance s wi hou conside ing he iming
o diagnosis.
Resul s
The SMRs and SIRs o all cance s combined (cance s a all
si es) and o gas ic cance sepa a ely in bo h s udy coho s
a e p esen ed in Table 2. SMR o gas ic cance (0.53) was
signi ican ly below uni y in he a ende coho and i was
highe in he nona ende s coho (SMR 1.28). The SMR o all
cance s in he a ende coho was 0.91 and in he nona -
ende s coho 1.45.
The SIRs o all cance s we e oughly simila in bo h s udy
coho s. Howe e , in he a ende coho , he SIR o s omach
cance was lowe han expec ed (0.75, 95% CI 0.57–0.95) and
ACTA ONCOLOGICA 919
i was lowe in he a ende s han in he nona ende s coho
(0.88, 95% CI 0.56–1.32) (Table 2).
The PYLL alue o gas ic cance was signi ican ly lowe
among he a ende s (27.7, 95% CI 15.5–36.0) han among
he nona ende s (77.3 95% CI 43.1–111.4) coho (Table 3).
Again, he PYLL alue o all cance s was lowe in he
a ende coho han in he nona ende s coho bu his di -
e ence was smalle han he di e ence in PYLL o gas ic
cance .
The c ude and co ec ed e ec s o sc eening on mo ali y
and p olonga ion o li e a e gi en in Table 4. The ela i e
dec ease in SMR a ibu able o SPGI sc eening o gas ic
cance esul ed in a alue 0.59 o he c ude p opo ion (E1).
The co esponding c ude a ibu able p opo ion o PYLL
was 0.67. A e co ec ing o selec ion bias, he co ec ed
a ibu able p opo ions (E2) o SMR and PYLL we e 0.23 and
0.39, espec i ely (Table 4).
Discussion
Gas ic cance is one o he common cance s wi h high mo -
ali y wo ldwide. The age-adjus ed incidence a e (wo ld
s anda d) in 2013 among Finnish men was 6 pe 100 000
pe son yea s, which is one- en h o he espec i e a e in he
1950s [10]. The li e expec ancy o pa ien s wi h gas ic cance
is no long, unless he cance is diagnosed in i s ea ly s age.
In 2009–2013, he i e-yea ela i e su i al a io in males
wi h s omach cance in Finland was 23% [10]. Abou a hal
o gas ic cance s, being mos o en o he so-called in es inal
ype, a e conside ed o de elop in AG and an acid- ee s om-
ach ia he ‘Co ea cascade’[11–14]. The e o e, ea ly iden i i-
ca ion and endoscopy o subjec s wi h AG may acili a e he
diagnosis o gas ic cance a an ea ly s age, and may enable
ea men o p emalignan gas ic lesions (in amucosal neo-
plasias) in an asymp oma ic phase [6–9]. A low se um le el
o pepsinogen I (SPGI) is a eliable bioma ke o AG and is,
he e o e, a ool o nonin asi ely delinea e subjec s wi h
ad anced AG who need a p omp diagnos ic uppe GI endos-
copy because o inc eased cance isk [1–4]. Co espondingly,
i is concei able ha an ea ly diagnosis o AG wi h a bio-
ma ke es ollowed wi h a diagnos ic uppe GI endoscopy
will imp o e he cance su i al, esul ing also in dec ease o
p ema u e mo ali y.
In o de o de elop a p og am o sc eening o s omach
cance by a bioma ke , his s udy comp ised a la ge popula-
ion-based sample o men bo n in 1929–1943 who we e
in i ed o sc eening by SPGI/endoscopy in 1994–1996 in wo
Finnish ci ies. This sc eening p og am applying a simple SPGI
bioma ke blood es was well accep ed wi h a high pa ici-
pa ion pe cen age (72%) and he sc eening p ocess was
adequa e. He e we e alua e whe he he design was
adequa e o e alua ion o he e icacy o he sc eening p o-
g am by gas ic cance mo ali y.
Biases be ween he a ende s and nona ende s coho s
cons i u e a dilemma in assessmen o he e icacy o he
sc eening. Because he sc eening ial could no be imple-
men ed o allow compa ison o in i ed and non-in i ed
g oups o men, he only op ion was o y o co ec o he
e ec s o selec i e a endance a e wa ds using gene al indi-
ca o s o cance equency and mo ali y in he ca ego ies o
be compa ed.
In gene al, he epo s o sc eening p og ams on cance s
do no include da a o a emp s o co ec o selec ion
biases e en hough hey a e ce ainly no ewo hy in all
sc eening p ojec s [8,15]. The men who did no wan o pa -
icipa e in he SPGI es may ha e been less in e es ed in
heal h issues in gene al han hose who pa icipa ed and
we e, he e o e, mo e liable o ea ly dea h om gas ic can-
ce and o high mo ali y om any cause o dea h [16–20].
The men in he p esen nona ende coho had a clea ly
highe incidence (SIR) o gas ic cance and o all cance s
han hose in he a ende coho . In spi e o he co ec ions
a e wa ds, he e may s ill emain biases ha could no be
aken in o accoun .
Table 3. Po en ial yea s o li e los (PYLL alues) pe 1000 pe sons and mean PYLL alues pe dea h be o e age o 80 among he sc eened
and non-sc eened men by si e o cance 1994–2011.
Sc eened (n¼12,175) Non-sc eened (n¼4697)
Cance si e PYLL 95%CI PYLL/dea h PYLL 95%CI PYLL/dea h
Gas ic cance 25.7 15.5–36.0 10.4 77.3 43.1–111.4 15.1
All cance s 875 815–935 11.0 1388 1259–1518 13.2
Table 4. C ude and co ec ed p opo ions (%) in educ ion o
mo ali y and o po en ial yea s o li e los (PYLL) among men
a ibu able o SPGI sc eening.
A ibu able p opo ion (%)
Ou come indica o C ude (E1) Co ec ed (E2)
Mo ali y 59 23
PYLL 67 39
Table 2. S anda dized mo ali y a ios (SMR) and s anda dized incidence a ios (SIR) among he sc eened and non-sc eened men by he si e o cance
1994–2011.
Sc eened (N¼12,175) Non-sc eened (n¼4697)
Cance si e E en OBS EXP SMR o SIR 95%CI OBS EXP SMR o SIR 95%CI
S omach cance Dea hs 31 58.1 0.53
a
0.36–0.75 24 18.7 1.28 0.82–1.90
Cases 60 80.5 0.75 0.57–0.95 23 26.1 0.88 0.56–1.32
All cance s Dea hs 1 020 1 116.7 0.91 0.86–0.97 514 354.8 1.45 1.33–1.57
Cases 3 088 2 747.6 1.12 1.08–1.16 976 881.4 1.11 1.04–1.17
a
p<0.001.
920 I. VOHLONEN ET AL.

The p esen s udy sugges s ha bioma ke sc eening by
SPGI may educe mo ali y om gas ic cance by one- i h
o e 15 yea s. Co espondingly, sc eening was es ima ed o
educe he po en ial yea s o li e-los (PYLL) due o gas ic
cance by almos 40%. These es ima es we e, howe e , incon-
clusi e due o me hodological issues as desc ibed abo e.
In ou s udy, wo cases o gas ic cance we e ound by
sc eening in men wi h low SPGI in 1994-1996, and bo h
pa ien s died om gas ic cance wi hin 5 yea s. The e o e,
he long e m dec ease in mo ali y be ween 1994 and 2011
was likely due o ea men o p e-cance ous lesions
obse ed in sc eening endoscopy o we e due o e adica ion
o he on-going Helicobac e pylo i in ec ion [16–20]. I can
be assumed ha he p ecance ous lesions in an a ophic
s omach mucosa de elop o in asi e cance s du ing li e- ime
in up o one hi d o cases i he lesions a e no p ope ly
ea ed [20].
In ou s udy, he expec ed numbe o dea hs due o gas-
ic cance was 58 and his numbe was based on a o ecas
made on he basis o he Finnish Cance Regis y. In he
sc eening o gas ic cance by a bioma ke , we ound 56
lesions and 2 cases o gas ic cance . In his iew, expec ed
and obse ed cases o gas ic cance we e simila .
This obse a ion indica es, ha a leas some 20 men
would be a isk o gas ic cance among he 56 men who
we e diagnosed wi h a p ecance ous lesion. Based on he
obse ed gas ic cance dea hs, he c ude a ibu able p o-
po ion in educ ion o dea hs due o gas ic cance was 59%
and he e o e 16 dea hs due o gas ic cance we e p e-
en ed i a endance was no selec i e. Because o selec ion,
we co ec ed i in he analyzes and he co ec ed a ibu able
p opo ion was 23% wi h he obse ed educ ion o 6 dea hs
due o gas ic cance . We canno ega d his igu e as an
unbiased one, because he unknown po en ial o esidual
con ounding a e he me hodological co ec ions. Hence we
do no know whe he he sc eening o gas ic cance was
e icacious o no .
Analyzes o he e ec s o SPGI sc eening on p ema u e
gas ic cance mo ali y using PYLL ga e esul s consis en
wi h hose ob ained by cance mo ali y. The co ec ed a ib-
u able p opo ion o SPGI sc eening in educ ion o PYLL o
gas ic cance was 39%. PYLL is dependen on he alue o
li e expec ancy selec ed o he calcula ions. In he p esen
in es iga ion, a li e expec ancy o 80 yea s was selec ed.
Dea hs be o e his age a e conside ed p ema u e and mos
dea hs due o gas ic cance in Finland occu be o e age
o 80.
The g ea e educ ion in co ec ed a ibu able p opo ion
in educ ion o PYLL han o SMR o gas ic cance (39% s.
23%) may indica e ha some cance ous lesions among he
a ending we e obse ed and ea ed in ea ly and cu able
s ages.
In spi e o he associa ion be ween SPGI sc eening and
dec eased gas ic cance mo ali y and PYLL, he p esen
esul s may s ill be biased al hough me hodological co ec-
ions we e done o co ec o con ounding. The e o e, he
p esen esul s do no jus i y de ini i e conclusions o imple-
men a ion o gene al sc eening p og ams. In o ma ion on
e icacy o a new and po en ial sc eening echnology o
cance needs o be based on well-designed s udy p o ocols
which esul in unbiased e idence. The e o e, con olled and
andomized sc eening s udies a e an ul ima e p e equisi e. In
he de eloped coun ies, incidence o gas ic cance is
dec easing along wi h H. pylo i in ec ion and AG, bu in he
de eloping coun ies hese a e s ill majo public heal h
p oblems.
Acknowledgmen s
P o esso Ma i H€
a k€
onen and P o esso Pen i Sipponen a e sha eholde s
o Biohi Oyj, a company which de elops and ma ke s labo a o y es s,
including bioma ke es s o s omach diseases.
Disclosu e s a emen
The au ho s epo no con lic s o in e es .
Re e ences
[1] S o sk ubb T, A o P, Ronkainen J, e al. Se um bioma ke s p o ide
an accu a e me hod o diagnosis o a ophic gas i is in a gen-
e al popula ion: he Kalixanda s udy. Scand J Gas oen e ol.
2008;43:1448–1455.
[2] Miki K, Mo i a M, Sasajima M, e al. Use ulness o gas ic cance
sc eening using he se um pepsinogen es me hod. Am J
Gas oen e ol. 2003;98:735–739.
[3] Dinis-Ribei o M, Yamaki G, Miki K, e al. Me a-analysis on he al-
idi y o pepsinogen es o gas ic ca cinoma, dysplasia o
ch onic a ophic gas i is sc eening. J Med Sc een. 2004;11:
141–147.
[4] Sacke DL, Holland WW. Con o e sy in he de ec ion o disease.
Lance . 1975;2:357–359.
[5] Teppo L, Pukkala E, Leh onen M. Da a quali y and quali y con ol
o a popula ion-based cance egis y. Expe ience in Finland. Ac a
Oncol. 1994;33:365–369.
[6] Ah ens W, Pigeo I, edi o s. Handbook o epidemiology. Be lin:
Sp inge ; 2005.
[7] Cambell DT, S anley JC. Expe imen al and quasi-expe imen al
designs o esea ch. Chicago (IL): Rand McNally; 1966.
[8] Coch ane AL, Holland WW. Valida ion o sc eening p ocedu es. B
Med Bull. 1971;27:3.
[9] Holland WW, S ewa d S. Sc eening in heal h ca e. London: The
Nu ield P o incial Hospi als T us ; 1990.
[10] Engholm G, Fe lay J, Ch is ensen N, e al. Gas ic p ecance ous
p ocess in a high isk popula ion: coho ollow-up. Cance Res.
1990;50:4737–4740.
[11] Co ea P, Piazuelo MB. The gas ic p ecance ous cascade. J Dig
Dis. 2012;13:2–9.
[12] Haenszel W, Co ea P, Cuello C, e al. Gas ic cance in Colombia.
II. Case-con ol epidemiologic s udy o p ecu so lesions. J Na l
Cance Ins . 1976;57:1021–1026.
[13] Sipponen P, Kekki M, Haapakoski J, e al. Gas ic cance isk in
ch onic a ophic gas i is: s a is ical calcula ions o c oss-sec ional
da a. In J Cance . 1985;35:173–177.
[14] Va is K, Sipponen P, Laxen F, e al. The Helsinki Gas i is S udy
G oup. Implica ions o se um pepsinogen I in ea ly endoscopic
diagnosis o gas ic cance and dysplasia. Scand J Gas oen e ol.
2000;35:950–956.
[15] Jang JS, Choi SR, Qu eshi W, e al. Long- e m ou comes o endo-
scopic submucosal dissec ion in gas ic neoplas ic lesions a a
single ins i u ion in Sou h Ko ea. Scand J Gas oen e ol.
2009;44:1315–1322.
[16] De V ies AC, Kuipe s EJ. Epidemiology o p emalignan gas ic
lesions: implica ions o he de elopmen o sc eening and su -
eillance s a egies. Helicobac e . 2007;12:22–31.
ACTA ONCOLOGICA 921
[17] C umley AB, Going JJ, McEwan K, e al. Endoscopic mucosal esec-
ion o gas oesophageal cance in a U.K. popula ion. Long- e m
ollow-up o a consecu i e se ies. Su g Endosc. 2011;25:543–548.
[18] Ichinose M, Yahagi N, Oka M, e al. Sc eening o gas ic cance in
Japan. In: Wu GY, Aziz K, edi o s. Cance sc eening. A p ac ical
guide o physicians. Po owa (NJ): Humana P ess; 2001. p. 87–102.
[19] Benichou J, Pal a M. Ra es, isks, measu es o associa ion and
impac . In: Ah ens W, Pigeo I, edi o s. Handbook o epidemi-
ology. Be lin: Sp inge ; 2005. p. 8–146.
[20] Wilson JMG, Junge G. P inciples and p ac ice o sc eening
o disease. Public Heal h Pape Numbe 34. Gene a: WHO;
1968.
922 I. VOHLONEN ET AL.