thyroid cancer risk from in utero exposure to chernobyl fallout maureen hatch workshop on radiation...

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Thyroid Cancer Risk from In Utero Exposure to Chernobyl Fallout Maureen Hatch Workshop on Radiation and Thyroid Cancer Tokyo, Japan 22 February 2014

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Thyroid Cancer Risk from In Utero Exposure to Chernobyl Fallout

Maureen Hatch

Workshop on Radiation and Thyroid CancerTokyo, Japan

22 February 2014

• April 26, 1986 accident at ChNPP

• Principal radionuclide: Iodine-131 (I-131)

• I-131 concentrates in the thyroid gland

Chernobyl Nuclear Reactor Accident

Exposure to the Embryo/Fetus

• I-131 uptake begins ~10-12 weeks gestation• Uptake increases faster than thyroid mass

• In late gestation, fetal I-131 levels many-fold higher than maternal levels

• I-131 readily crosses the placenta

Potential Radiosensitivity of the Fetus

• Small thyroid mass

• Rapid cell division

4

Chernobyl Accident Fallout: Ukraine

< 3 7 k B q m -2

5 5 5 -1 4 8 0 k B q m1 4 8 0 -3 7 0 0 k B q m -2-2

-2 3 7 -1 8 5 k B q m1 8 5 -5 5 5 k B q m -2

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Ok a

O R SH A

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B aranov ich i

SM O L E N S K

B RYA N SK

K A L U G AT U L A

O R E L

K U R SK

PO LTAVA

K H A R K O V

C H E R K A S SY

Z H IT O M IR

R O V N O

Te rn o p o l

K h m e ln itsk iy V IN N IT S A

B erd ich evB e lay a Tserk ov

P in sk

L id a

M o lod ech n oB o riso v

M o zy r

N o v o z y b k o v

K ric h e vC h erik o vB y k ho v

G o rk i

R o s la v l

K iro v

L y u d in o v o

D y a tlo v o

B o lk h o vM ts e n s k

P la v s k

A le k s in

K im o v s k

N o v o-m o sko v sk

K h o yn ikiB rag in

C h ern ob y lP o le ssk oje

N aro d ic h i

K o ro s te n

N o v og rad Vo ly n sk iy

S a rn yO v ru ch P rip y a t

S h o s tk a

S lu tsk

S o lig o rsk

N o v og rud o k

C H E R N IG O V

G O M E L

SU M Y

B E L G O R O D

V IL N IU S

M O G IL E V

K IEV

M IN SK

B E L A R U S

U K R A I N E

R U S S I A

E fre m o v

S lav utich

N aro v ly a

B o b ru y sk

Ukraine-American In Utero Study:Objectives

• Estimate risk of thyroid cancer

• Explore incidence of non-thyroid cancer

Ukraine-American In Utero Study: Methods

• For thyroid cancer:

-in-depth screening examinations, 2003-2006

-in-person mother-child interviews

• For non-thyroid cancer:

-record linkage, National Cancer Registry,

1997-2009

• Study area: most affected northern oblasts,

• 2,582 mother-child pairs: Women pregnant on April 26,1986 or the two months following

-1,494 from contaminated areas

-1, 088 from no/low-contaminated areas

(Hatch et al., JCEM, 2009; Likhtarov et al., Health Phys, 2011)

Ukraine-American In Utero Study:Design

Distribution of I-131 Thyroid Dose Estimates

Trimester ATA N Mean, mGy

‘Contaminated’ group

1 400 3.7

2 575 104.2

3 469 206.5

‘Comparison’ group

1 321 0.3

2 276 7.0

3 419 13.1

Statistical Methods

• Estimated EOR/Gy for thyroid cancer

(linear logistic regression models)

sensitivity analyses comparison of radiosensitivity

• Estimated SIRs for non-thyroid cancers

(indirect standardization)

Screening Cases with Thyroid Neoplasia

# Dx Source of dx

Trimester ATA

Sex Age, yr

I-131 dose, mGyTotal Postnatal

1 PTC1 PMC4 3 F 19.9 18.6 4.2

2 PTC PMC 3 F 19.8 421.2 395.2

3 PTC PMC 3 F 19.8 453.6 3.6

4 PTC PMC 3 F 17.7 16.2 0

5 PTC FNA5 2 F 16.5 139.3 0

6 PTC FNA 2 F 20.9 86.4 0

7 FTC2 PMC 1 F 19.4 3.1 0

8 HCN3 FNA 2 M 20.8 33.0 0

1PTC, papillary thyroid cancer. 2FTC, follicular thyroid cancer. 3HCN, Hurthle cell neoplasm. 4PMC, pathomorpology. 5FNA, fine needle aspiration biopsy.

Results: Thyroid Cancer

Outcome EOR1/Gy 95% CI P

In utero

Thyroid cancer or neoplasia3 (n=8)

5.35 NE2-77.29 0.24

Thyroid cancer4 (n=7) 11.66 NE-1,982 0.12

1-5 year old

Thyroid cancer (n=13) 3.24 NE-539 0.01

1Adjusted for sex and age. 2NE, not estimable. 3Exclusion of one case with postnatal I-131 dose > 30 mGy or one case exposed during 1st trimester had little influence on EOR/Gy.4Hurthle cell neoplasm excluded.

Registry-linked Non-thyroid Cancers: 1997-2009

# Diagnosis Trimester ATA

Sex Age, yr

I-131 dose, mGy

1 Hodgkin’s disease 3 M 18.3 309.7

2 Hodgkin’s disease 2 F 20.4 18.4

3 Hodgkin’s disease 1 M 15.7 0

4 Brain cancer, NOS1 3 F 12.3 3.8

5 Diffuse astrocytoma 1 F 14.2 0

6 Choriocarcinoma 2 F 22.1 66.9

1NOS, not specified.

Results: Non-thyroid Cancers

Categories O E1 SIR (O/E)

95% CI

All 6 5.0 1.20 0.47-2.42

Lymphoma 3 1.3 2.28 0.57-5.90

Leukemia 0 0.8 0.00 0.00-2.52

1Estimated by applying sex- and age-specific cancer rates to person-years at risk (assuming different scenarios for losses to follow-up).

Chernobyl Accident Fallout: Belarus

< 3 7 k B q m -2

5 5 5 -1 4 8 0 k B q m1 4 8 0 -3 7 0 0 k B q m -2-2

-2 3 7 -1 8 5 k B q m1 8 5 -5 5 5 k B q m -2

P r i p y a t

Dr

n ep -B u g s k i C a na lP r i p y a t

S to

k ho

d

Go

r yn

Be

rezi

na

De s

na

T e t er e

v

De s

na

D n e p r

D n e p rR o s k a

S e y m

S o s n a

Os k

ol

Vo

r sk

l a

Ps e

l

S o z h

Ok a

Ok a

O R SH A

Yele ts

B aranov ich i

SM O L E N S K

B RYA N SK

K A L U G AT U L A

O R E L

K U R SK

PO LTAVA

K H A R K O V

C H E R K A S SY

Z H IT O M IR

R O V N O

Te rn o p o l

K h m e ln itsk iy V IN N IT S A

B erd ich evB e lay a Tserk ov

P in sk

L id a

M o lod ech n oB o riso v

M o zy r

N o v o z y b k o v

K ric h e vC h erik o vB y k ho v

G o rk i

R o s la v l

K iro v

L y u d in o v o

D y a tlo v o

B o lk h o vM ts e n s k

P la v s k

A le k s in

K im o v s k

N o v o-m o sko v sk

K h o yn ikiB rag in

C h ern ob y lP o le ssk oje

N aro d ic h i

K o ro s te n

N o v og rad Vo ly n sk iy

S a rn yO v ru ch P rip y a t

S h o s tk a

S lu tsk

S o lig o rsk

N o v og rud o k

C H E R N IG O V

G O M E L

SU M Y

B E L G O R O D

V IL N IU S

M O G IL E V

K IEV

M IN SK

B E L A R U S

U K R A I N E

R U S S I A

E fre m o v

S lav utich

N aro v ly a

B o b ru y sk

Belarus-Japanese In Utero Study

• Ultrasound thyroid screening study in 2000• School children living 150 km from ChNPP• Thyroid cancer pre/post-accident

• Shibata et al., Lancet 2001

16

Belarus-Japanese In Utero Study

• Group I: born before the accident • Group II: exposed in utero (N=2,409)• Group III: exposed post-natally

OR (II v I) = 11 (3-176)

OR (III v I) = 121 (9-31,000)

17

Belarus-American In Utero Study

• Cohort of 3000• Exposed In Utero • Gomel, Mogilev oblasts• Dose reconstruction for I-131 and Cs-137• Linkage with Belarusian Cancer Registry,

Chernobyl State Registry

• Currently in progress

18

Summary of Findings to Date:Thyroid Cancer Risk from In Utero Exposure

to Chernobyl Fallout

19

Collaborators

US

• Kiyo Mabuchi Belarus• Alina Brenner • Alexander Rozhko• Andre Bouville • Vasilina Evseenko• Vladimir Drozdovitch • Vladimir Masyakin Evgenia Ostroumova

• Olga Polyanskaya

• Victor Minenko

Ukraine

• Mykola Tronko

• Valery Tereschenko

• Tatiana Bogdanova

• Victor Shpak

• Olexandr Zvinchuk

• Anna Derevyanko

• Evgenie Gorokh

Thank you for your attention