3060
In oduc ion
In he hie a chy o epidemiological e idence on causes
o cance , longi udinal s udies (ei he nes ed case–con ol
o case–coho s udies) a e second only o andomized
ial e idence [1, 2]. The Finnish Ma e ni y Coho (FMC)
was es ablished in 1983 o p o ide a esou ce o such
s udies. All women in Finland a e a hei 12 h week o
p egnancy o e ed sc eening o congeni al in ec ions (hepa-
i is B, HIV, and syphilis). The esidual se um samples
a e s o ed in he FMC [3]. The e is a sepa a e legal basis
o he collec ion and scien i ic use o FMC (The law o
he Na ional Ins i u e o Heal h and Wel a e 668/2008).
Since 2001, a na ionwide in o med consen sys em based
on he op - ou p inciple wi h negligible d op ou has
been in ope a ion.
An example o pionee ing cance esea ch based on
he FMC a e longi udinal s udies documen ing ha
exposu e o human papilloma i us (HPV) ypes 16 and
18 causes an excess isk o la e de elopmen o bo h
ce ical, o he anogeni al and o opha yngeal cance s
[4–6]. FMC’s se ial samples ha e been use ul o dis-
en angling he empo al o de o e en s in ca cinogenesis,
o example, an agonis ic in e ac ion o di e en HPV
ypes [7], and disclosing smoking as an independen
isk ac o o ce ical cance [8]. The p ediagnos ic se ial
samples also enable s udies on he sensi i i y and speci-
ici y o bioma ke s o u u e cance diagnosis and
sc eening [9]. High- quali y da a on he ges a ional da e
o he sample collec ion enable s udies on ho mones
and cance [10]. The FMC is posi ioned as an in e -
na ional Open Access esou ce. Linkage o pe sonal
iden i ie s wi h he na ionwide, popula ion- based Finnish
Cance Regis y and o he popula ion- based heal h and
ial egis ies es ablishes a unique s udy base o lon-
gi udinal s udies [11].
METHODS
Cance Regis y ollow- up o 17 million pe son- yea s o a
na ionwide ma e ni y coho
Ma i Leh inen1,2,3 , Heljä-Ma ja Su cel3,4,5, Ka i Na unen1,3, Ee o Pukkala1,6 & Joakim Dillne 2,3
1Uni e si y o Tampe e, Tampe e, Finland
2Ka olinska Ins i u e, S ockholm, Sweden
3Eu opean Science In as uc u e Se ices EEIG, S ockholm, Sweden
4Na ional Ins i u e o Heal h & Wel a e, Helsinki, Finland
5Biobank Bo ealis o No he n Finland, Oulu Uni e si y Hospi al, Oulu, Finland
6Finnish Cance Regis y, Ins i u e o S a is ical and Epidemiological Cance Resea ch, Helsinki, Finland
© 2017 The Au ho s. Cance Medicine published by John Wiley & Sons L d.
This is an open access a icle unde he e ms o he C ea i e Commons A ibu ion License, which pe mi s 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.
Keywo ds
Biobank, cance causes, coho ,
epidemiology, umo ma ke s
Co espondence
Ma i Leh inen, Uni e si y o Tampe e, 33014
Tampe e, Finland. Tel: +358405437862;
Fax +358 3 2100004;
E-mail: [email p o ec ed]
Funding In o ma ion
NCI con ac : HHSN261201300016C
Recei ed: 4 Sep embe 2017; Accep ed: 10
Sep embe 2017
Cance Medicine 2017; 6(12):3060–3064
doi: 10.1002/cam4.1222
Abs ac
Popula ion- based Finnish Ma e ni y Coho (FMC) comp ises 2M i s imes e
se a collec ed om 1M women du ing 33 yea s. In o med consen is by he
op - ou p inciple, and linkages wi h cance and popula ion egis ies p o ide a
base o o e ime and o e gene a ion s udies. Follow- up o 17M pe son- yea s
by he end o 2014 can iden i y 39,700 cases o in asi e cance and 18,900 cases
o p emalignan b eas and ce ix lesions, and basal cell ca cinoma diagnosed
a e se um sampling. Fo women wi h mul iple p egnancies, se ial samples
aken be o e cance diagnosis a e a ailable. O sp ing o he women ha e
de eloped mo e han 4000 cance s. Fo 100,000 indi iduals, samples aken du -
ing he p egnancies o bo h hei mo he s and g andmo he s enable amilial
cance s udies. FMC con inues o collec samples, and su eillance o exposu es
o in e en ions like accina ion p og ams is easible. In summa y, he FMC is
a unique, accessible biobank o epidemiological, bioma ke , and su eillance
s udies on cance .
Cance
Medicine Open Access
3061
© 2017 The Au ho s. Cance Medicine published by John Wiley & Sons L d.
Cance Cases in Ma e ni y Coho M. Leh inen e al.
Table 1. Es ima ed1 numbe s o inciden in asi e cance cases in he Finnish Ma e ni y Coho 1983–2014.
P ima y si e ICD- 10 code
A e i s sample
(N = 953,000)
A e second sample
(N = 604,000)
A e hi d sample
(N = 240,000)
All si es C00–96, D32–33, D42–43,
D45–47, D76
39,700 19,900 6800
Mou h, pha ynx C00–14 490 220 85
Lip C00 10 5 1
Tongue C02 110 50 5
Mou h, o he C03–06 110 50 15
Sali a y glands C07–08 110 50 20
Pha ynx C01, C09–14 130 55 20
Diges i e o gans C15–26 3900 1900 700
Esophagus C15 65 30 10
S omach C16 550 280 95
Small in es ine C17 110 55 20
Colon C18 1400 700 250
Rec um, ec osigmoid,
anus
C19–20 790 380 130
Li e C22 135 50 20
Gallbladde , bile duc s C23–24 140 60 20
Panc eas C25 530 230 85
O he diges i e o gans C26 30 10 0
Respi a o y o gans C30–39 1050 420 130
Nose, sinuses C30–31 35 15 5
La ynx, epiglo is C32 15 5 2
Lung, achea C33–34 980 350 110
Medias inum, pleu a C38 10 8 4
Bone C40–41 90 40 10
Melanoma o he skin C43 2200 1200 430
Skin, nonmelanoma C44 400 180 60
Meso helioma C45 20 9 3
Au onomic ne ous sys em C47 10 4 0
So issues C48–49 280 140 60
B eas C50 18,400 9200 3000
Female geni al o gans C51–58 3800 1700 550
Ce ix u e i C53 1130 630 260
Co pus u e i C54 1100 400 130
U e us, o he C55, C58 20 5 1
O a y C56 1100 500 150
O he emale geni al C51–52, C57 280 110 25
Placen a 15 4 2
U ina y o gans C64–68 900 400 160
Kidney C64 620 290 120
Bladde and u ina y ac C65–68 270 110 40
Eye C69 70 30 10
B ain, cen al ne ous
sys em
C70–72, D32–33, D42–43 2500 1400 500
Thy oid gland C73 2300 1300 520
O he endoc ine glands C74–75 50 20 5
Ill de ined o unknown C76, C80 300 130 40
Lymphoid and hema opoi-
e ic issue
C81–96, D45–47, D76 2600 1300 430
Hodgkin lymphoma C81 350 180 55
Non- Hodgkin lymphoma C82–86, C96, D76 1200 600 200
Myeloma C90 220 100 25
Leukemia C91–95 600 300 90
196% o he Finnish p egnan women be ween 1983 and 2016 ha e consen ed o pa icipa e in he FMC. As he women can wi hd aw consen a
will he numbe s should be conside ed as es ima es.
3062 © 2017 The Au ho s. Cance Medicine published by John Wiley & Sons L d.
M. Leh inen e al.Cance Cases in Ma e ni y Coho
Ma e ial and Me hods
A he end o 2016 he FMC comp ised 2.0 million se um
samples om abou 1 million women. As he congeni al
sc eening is epea ed on each p egnancy, se ial samples
a e a ailable o abou 50% o he women. Mo eo e ,
he e a e app oxima ely 100,000 pai s o mo he s and
daugh e s, who bo h ha e dona ed se a o he FMC o
scien i ic esea ch.
We es ima ed he numbe s o inciden cance cases in
he FMC (Table 1). Cance incidence in he FMC is simila
o ha in he gene al emale popula ion o all cance
ypes [11], wi h he excep ion o endome ial cance which
is dec eased (43%) due o p o ec ion om p egnancy.
Thus, i was possible o es ima e he numbe o cance
cases by mul iplying he pe son- yea s gene a ed by women
in FMC by he end o yea 2014 wi h cance incidence
a e in he Finnish emale popula ion in each 5- yea age
ca ego y (www.cance egis y. i).
Resul s
The e a e app oxima ely 40,000 p ospec i ely occu ing
cases o cance wi hin 17.2 million pe son- yea s o ollow-
up up o 2014. Du ing he i s 5 yea s a e p egnancy,
he numbe o new cance cases is mode a e bu inc eases
when he women become olde . B eas cance comp ised
almos hal o all inciden in asi e cance cases iden i ied
(18,400 cases, Table 1).
The nex 10 mos common cance ypes we e as ol-
lows: hy oid cance (2300 cases), melanoma (2200 cases),
colo ec al cance s (2190 cases), lymphomas (1550 cases),
ce ical cance (1130 cases), endome ial cance (1100
Table 2. Es ima ed1 numbe s o inciden in asi e cance cases in he o sp ing o he Finnish Ma e ni y Coho pa icipan s (FMC) 1983–2014.
Cance ype ICD10
Boys Gi ls All
0–4 5–9 1 ± 14 0–14 0–4 5–9 10–14 0–14 0–4 5–9 10–14 0–14
All si es C00–96,
D32–33,
D42–43,
D45–47, D76
1180 535 445 2160 1020 420 410 1850 2200 955 855 4010
Mou h, pha ynx C00–14 <5 <5 10 10 0 <5 5 10 <5 5 15 20
Diges i e o gans C15–26 20 10 25 60 15 10 45 70 35 25 70 130
Respi a o y
o gans
C30–39 10 <5 5 15 10 5 0 15 15 10 5 30
Female geni al
o gans
C51–58 10 5 20 35 10 5 20 35
Male geni al
o gans
C60–63 30 5 5 40 30 5 5 40
U ina y o gans C64–68 110 20 5 135 105 20 5 130 220 40 10 270
Melanoma o
he skin
C43 5 5 15 20 0 5 10 15 5 10 20 35
Skin,
nonmelanoma
C44 0 5 5 10 5 0 5 5 5 5 5 15
Eye C69 55 5 5 65 45 5 5 50 105 5 5 115
Thy oid gland C73 5 5 5 15 0 5 15 20 5 10 20 35
O he endoc ine
glands
C74–75 90 10 10 110 90 5 5 100 180 15 15 210
Bone C40–41 5 15 25 45 15 10 25 50 15 20 55 90
So issues C48–49 40 20 15 75 45 20 10 75 90 35 30 155
Ill de ined o
unknown
C76, C80 5 5 5 15 5 5 5 15 10 10 5 25
Au onomic
ne ous sys em
C47 40 5 5 50 40 5 5 50 80 5 5 90
B ain, CNS C70–72,
D32–33, 42–43
265 185 140 590 195 145 115 455 460 330 260 1050
Lymphoid,
hema opoe ic
issue
C81–96,
D45–47, D76
500 235 175 910 445 175 155 770 940 410 325 1675
196% o all Finnish p egnan women be ween 1983 and 2014 ha e consen ed o pa icipa e in he FMC. As he women can la e wi hd aw consen
a will he numbe s should be conside ed as es ima es.
3063
© 2017 The Au ho s. Cance Medicine published by John Wiley & Sons L d.
Cance Cases in Ma e ni y Coho M. Leh inen e al.
cases), o a ian cance (1100 cases), lung cance (980 cases),
kidney cance (620 cases), and leukemia (600 cases).
Nonin asi e cance s include 10,000 cases o in si u ce i-
cal cance , 7400 cases o basal cell ca cinomas, and 1500
cases o in si u b eas ca cinomas.
The numbe o childhood cance cases in he o sp ing
o he FMC dono s (4000 cases) is sizeable (Table 2).
Especially, he numbe s o childhood leukemias and lym-
phomas (al oge he mo e han 1600 cases) a e high (Table 2).
Discussion
Cance incidence in he FMC is simila o ha in he
gene al emale popula ion o all cance ypes [11], wi h
he excep ion o endome ial cance which is dec eased
(43%) due o p o ec ion om p egnancy. Wi h only 20
women op ing ou in 2017, he popula ion- based na u e
o FMC emains i ually in ac .
In addi ion o longi udinal s udies on cance e iology
and sc eening s udies, he esou ce is also po en ially use-
ul o s udies on gene ic cance isk. Howe e , he i s
imes e se um samples con ain measu able amoun s o
e al DNA, which needs o be con olled o in gene ic
s udies [12]. Because he FMC is na ionwide and con ains
samples om 94% o all Finnish p egnan women [11],
e y la ge- scale o e - gene a ion s udies can be designed
by linking he iden i ies o he mo he s o hei o sp ing
and/o ela i es [13]. Due o he long his o y o he FMC,
p ospec s o s udying congeni al causes o cance in he
o sp ing o he women in FMC a e also good.
Ongoing FMC p ojec s include s udies o he possible
ole o he same mic obiome, ha is, simila se ological
signa u e o mo he s and daugh e s wi h he same cance
o he same ypes o Chlamydia achoma is [14], HPV
[7], Helicobac e pylo i, o S ep ococcus galoly icus in amilial
ce ical, colo ec al, and s omach cance s, espec i ely.
The FMC sample collec ion can also suppo clinical
ials and su eillance pu poses, including cance con ol.
Fo example, we a e cu en ly compa ing he long- e m
s abili y o an ibody esponses induced by ei he quad-
i alen o bi alen accines agains HPV among women
who pa icipa ed as adolescen s in la ge andomized albei
popula ion- based ials o hese accines [15]. By linking
he clinical ial iles o he FMC iles, i has been pos-
sible o iden i y se um samples collec ed up o 14 yea s
pos accina ion. E alua ion o accine- induced an ibody
esponse in ye - o- be- iden i ied b eak h ough cases makes
sea ch o co ela es o p o ec i e immuni y easible.
This coho p o ile desc ibes he basic cha ac e is ics
o he FMC and p o ides some examples o i s po en ial
use. The FMC is also a ole model in s ic sa e gua d-
ing o in eg i y and compliance wi h da a p o ec ion
laws. While linkages o cou se need o be pe o med
wi h iden i iable da a, once he samples a e e ie ed
hey a e pseudonymized and i is no possible o link
he esea ch da a o an iden i iable indi idual. To p o-
mo e he use o he FMC as an in e na ional esou ce
o epidemiological cance esea ch, an in e na ional
nonp o i company (ESIS EEIG) specializing in assis ing
in e na ional esea che s wi h he da a and samples hey
need has been ounded and is a ailable o acili a e he
o mal and logis ic p ocess o ob ain access o he sam-
ples and da a ha in e na ional cance esea ch may
need (www.esis. i).
Acknowledgmen s
We hank P. Koskela, who o iginally es ablished he FMC
Biobank.
Con lic s o In e es
None decla ed.
Re e ences
1. Hill, A. B. 1965. The en i onmen and disease:
associa ion o causa ion. P oc. R. Soc. Med. 58:295–300.
2. Doll, R., and R. Pe o. 1981. Causes o cance . J. Na l.
Cance Ins . 166:1191–1308.
3. Koskela, P., T. An ila, T. Bjo ge, A. B uns ig, J.
Dillne , M. Hakama, e al. 2000. Chlamydia achoma is
in ec ion is a isk ac o o ce ical cance . In . J.
Cance 85:35–39.
4. Dillne , J., M. Leh inen, T. Bjo ge, T. Luos a inen, L.
Youngman, E. Jellum, e al. 1997. A p ospec i e
se oepidemiological s udy o human papilloma i us
in ec ion as a isk ac o o in asi e ce ical cance . J.
Na l. Cance Ins . 89:1293–1299.
5. Bjo ge, T., J. Dillne , T. An ila, V. Abele , A. Engeland,
T. Hakulinen, e al. 1997. A p ospec i e
se oepidemiological s udy o human papilloma i us and
non- ce ical anogeni al cance s. BMJ 315:646–649.
6. Mo k, J., A.-K. Lie, E. Gla e, S. Cla k, G. Hallmans,
E. Jellum, e al. 2001. A p ospec i e s udy on human
papilloma i us as a isk ac o o head and neck
cance . N. Engl. J. Med. 344:1125–1231.
7. Luos a inen, T., P. Namujju, M. Me ikukka, H. M.
Su cel, T. Hakulinen, J. Dillne , e al. 2013. O de o
p e alen /inciden sexually ansmi ed in ec ions and he
isk o CIN g ade 3. In . J. Cance 133:1756–1760.
8. Kapeu, A., L. Youngman, E. Jellum, J. Dillne , M.
Hakama, P. Koskela, e al. 2009. Smoking is an
independen isk ac o o ce ical cance . Am. J.
Epidemiol. 169:480–488.
9. Leh inen, M., P. Koskela, H. Ögmundsdo i , A. Bloigu,
J. Dillne , M. Gudnado i , e al. 2003. Ma e nal
3064 © 2017 The Au ho s. Cance Medicine published by John Wiley & Sons L d.
M. Leh inen e al.Cance Cases in Ma e ni y Coho
he pes i us in ec ions and isk o acu e lymphoblas ic
leukaemia in he o sp ing. Am. J. Epidemiol.
158:207–213.
10. Fo ne , R., H. Schock, R. Kaaks, M. Leh inen, E.
Pukkala, H. Å. Lakso, e al. 2017. Human ch onionic
gonado opin and ma e nal b eas cance : a nes ed
case- con ol s udy in he Finnish Ma e ni y Coho .
Can. Res. 77:134–141.
11. Pukkala, E., A. Ande ssen, G. Be glund, R. Gisle oss, V.
Gudnason, G. Hallmans, e al. 2007. No dic biological
specimen banks as basis o s udies o cance causes
and con ol – mo e han 2 million sample dono s,
25 million pe son yea s and 100,000 p ospec i e cance s.
Ac a Oncol. 46:286–307.
12. Sjöholm, M. I., G. Ho man, S. Lindg en, J. Dillne ,
and J. Ca lson. 2005. Compa ison o a chi al plasma
and o malin- ixed pa a in- embedded issue o
geno yping in hepa ocellula ca cinoma. Cance
Epidemiol. Bioma ke s P e . 14:251–255.
13. Leh inen, M., M. Pawli a, K. Zumbach, M. Hakama, E.
Jellum, P. Koskela, e al. 2003. E alua ion o an ibody
esponse o human pilloma i us ea ly p o eins in
women who de eloped ce ical cance 1- 20 yea s la e .
Am. J. Obs e . Gynecol. 88:49–55.
14. An ila, T., P. Saikku, P. Koskela, A. Bloigu, J. Dillne ,
I. Ikäheimo, e al. 2001. Se o ypes o Chlamydia
achoma is and isk o ce ical squamous cell
ca cinoma. JAMA 285:46–51.
15. Leh inen, M., and J. Dillne . 2013. Clinical HPV
accina ion ials and beyond. Na . Re . Clin. Oncol.
10:400–410.