1. Childhood Thyroid Cancer in Russia Following the Chernobyl accident V.K. Ivanov Chairman, Russian Scientific Commission on Radiological Protection Medical Radiological Research Center National Radiation and Epidemiological Registry Medical Radiological Research Center National Radiation and Epidemiological Registry The International Workshop on Radiation and Thyroid Cancer Japanese Ministry of the Environment (MoE) Fukushima Medical University (FMU) The OECD Nuclear Energy Agency (NEA) Tokyo, Japan, 21-23 February 2014

2. Questions… Increased thyroid cancer incidence in residents following the Chernobyl accident in their childhood Increased thyroid cancer incidence in residents exposed to radiation following the Chernobyl accident in their childhood Increase in background (non-radiation) thyroid cancer incidence radiation-induced + Estimating SCREENING EFFECT Estimating RADIATION RISK Why… & How estimate…?

4. NRER IS A PART OF MEDICAL RADIOLOGICAL RESEARCH CENTER OF THE RUSSIAN MINISTRY OF HEALTH The National Registry is the WHO Collaborating Centre for Research and Training in Radiation Epidemiology 23 regional centers 4 000 hospitals and clinics 798 000 registered persons 400 000 Individual doses 18 000 000 diagnoses NATIONAL RADIATION AND EPIDEMIOLOGICAL REGISTRY STRUCTURE OF THE REGISTERED PERSONS

5. COHORT SELECTED FOR ANALYSIS OF RADIATION RISK OF THYROID CANCER Size of Cohort: 309,130 individuals with known thyroid dose (people living in contaminated areas 137 Cs ≥ 5 Ci/km 2 ) Bryansk, Kaluga, Orel and Tula regions 1980 19861991 2008 registration of persons Start of follow-up End of follow-up 18 years Follow-up period: Age at exposure (1986), y RegisteredpersonsObservedcasesN%N 0-1797,19131 %247 18 +211,93969 %746 Total309,130100 %993 Cases: 993 Thyroid cancers (ICD-10: C73)

6. AVERAGE THYROID DOSES IN THE SETTLEMENTS OF BRYANSK, KALUGA, OREL AND TULA OBLASTS Ivanov VK, Kashcheev VV et al. Radiat Prot Dosimetry; 2012 Sep;151(3):489-99. The individualized thyroid doses for cohort members have been defined as equal to the average age-specific thyroid doses in their settlements at 1986, according to the Russian official catalogue of average doses of exposure of the thyroid gland.

7. METHODS: Excess relative risk (ERR) model – observed increase in thyroid cancer incidence rate 0 – baseline thyroid cancer incidence rate ERR – excess relative risk per 1 Gy d – average absorbed dose for the thyroid gland

8. METHODS: Baseline thyroid cancer incidence rate 0 rus – thyroid cancer incidence rate in Russia (SCREENING EFFECT) SIR – standardized incidence ratio (SCREENING EFFECT)

9. METHODS: Assessment of screening and dose response Thyroid dose, Gy SCREENING EFFECT ERR (dose response)

10. Follow-up: 1991 – 2008 Age at the time of the Chernobyl accident (years) 0-17 y18 y and older Number of persons97,191211,939 Number of cases247746 Mean dose in healthy cohort members (mGy)18837 Mean dose in cases (mGy)22532 SIR, SCREENING EFFECT (95% CI), p-value7.80 (5.95; 9.81), p<0.0013.73 (3.42; 4.07), p<0.001 ERR per 1 Gy (95% CI), p-value3.58 (1.61; 5.57), p<0.001-0.49 (-2.33; 1.36), p>0.5 SIR AND ERR OF THYROID CANCER IN REGISTERED POPULATION OF BRYANSK, KALUGA, OREL AND TULA OBLASTS Cohort: 309,130 individuals (993 cases of thyroid cancer)

11. Follow-up: 1991 – 2008 Age at the time of the Chernobyl accident (years) 0-17 y (boys)0-17 y (girls) Number of persons44,59852,593 Number of cases61186 Mean dose in healthy cohort members (mGy)178196 Mean dose in cases (mGy)250218 SIR, SCREENING EFFECT (95% CI), p-value10.55 (4.59; 17.80), p<0.0017.48 (5.58; 9.61), p<0.001 ERR per 1 Gy (95% CI), p-value6.70 (1.88; 23.13), p<0.0012.68 (0.66; 5.60), p<0.001 SIR AND ERR OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS (0-17 y in 1986) Sub-Cohort: 97,191 individuals (247 cases of thyroid cancer)

12. RELATIVE RISK OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS (in 1986) BY DOSE GROUPS AMONG CHILDREN AND ADOLESCENTS (in 1986) BY DOSE GROUPS Dose group (mGy) Mean dose (Gy) Number of cases Person-years RR (95% CI) p-value 0-0.050.02749288,2181 (Reference) 0.05-0.10.07253318,5361.01 (0.68; 1.49) > 0.5 0.1-0.150.12437212,4911.18 (0.77; 1.81) 0.46 0.15-0.20.17318131,2180.91 (0.52; 1.53) > 0.5 0.2-0.250.2221897,5001.64 (0.93; 2.76) 0.085 0.25-0.30.2731675,4202.15 (1.18; 3.69) 0.013 0.3-0.350.3241744,4323.12 (1.75; 5.30) < 0.001 0.35-0.50.4182094,7912.31 (1.35; 3.83) 0.003 > 0.50.86019107,5042.40 (1.36; 4.03) 0.002 Model of Relative Risk:

13. RELATIVE RISK OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS (0-17 y in 1986) BY DOSE GROUPS Internal control: 0-50 mGy * Dashed line is RR=1+ERR, where ERR (3.58, 95% CI:1.61-5.57)

14. EXPANDED STUDY OF SCREENING EFFECT AND RADIATION RISK OF THYROID CANCER Cohort of children and adolescents: 97,191 persons (0-17 y in 1986) (people living in contaminated areas 137 Cs ≥ 5 Ci/km 2 ) 1980 19861991 2008 registration of persons Start of follow-up End of follow-up 21 years Extended Follow-up period: Cases: 247 Thyroid cancers (ICD-10: C73) 2011 + 25 cases = 272 + 25 cases = 272 Tasks… SCREENING EFFECT as the function of time SCREENING EFFECT as the function of time Dose-response in low-dose range (< 250 mGy) Dose-response in low-dose range (< 250 mGy)

15. INCIDENCE RATE OF THYROID CANCER IN MALE POPULATION OF THE RUSSIAN FEDERATION

16. INCIDENCE RATE OF THYROID CANCER IN FEMALE POPULATION OF RUSSIAN FEDERATION

17. OBSERVED AND EXPECTED NUMBER OF THYROID CANCER CASES AMONG CHILDREN AND ADOLESCENTS (0-17 y. in 1986) BY CALENDAR PERIODS

18. SIR OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS AS A FUNCTION OF CALENDAR PERIOD IMPORTANT! SIR includes the radiation risk => SIR ≠ SCREENING

19. Follow-up: 1991 – 2011 0-17 y at the time of the Chernobyl accident published in RPDnew analysis Number of persons97,191 Number of cases247272 Mean dose in healthy cohort members (mGy)188 Mean dose in cases (mGy)225214 SIR, SCREENING EFFECT (95% CI), p-value7.80 (5.95; 9.81), p<0.0016.65 (5.15; 8.24), p<0.001 ERR per 1 Gy (95% CI), p-value3.58 (1.61; 5.57), p<0.0013.81 (1.81; 6.86), p<0.001 NEW ANALYSIS OF SIR AND ERR OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS Cohort of children and adolescents: 97,191 persons 272 cases of thyroid cancer 272 cases of thyroid cancer

20. Follow-up: 1991 – 2011 0-17 y at the time of the Chernobyl accident SCREENING EFFECT by periods, 95% CI 1991 – 199515.2 (10.6; 20.9) 1996 – 2000 7.5 (5.5; 9.9) 2001 – 2005 6.7 (5.1; 8.6) 2006 – 2011 7.0 (5.5; 8.8) ERR per 1 Gy (95% CI), p-value3.34 (1.39; 6.82), p<0.001 NEW ANALYSIS OF SIR AND ERR OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS Cohort of children and adolescents: 97,191 persons 272 cases of thyroid cancer 272 cases of thyroid cancer

21. NEW ANALYSIS OF SIR AND ERR OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS Cohort of children and adolescents: 97,191 persons 272 cases of thyroid cancer 272 cases of thyroid cancer (PURE EFFECT)

22. Dose range, mGyAverage thyroid dose, mGyCases ERR per 1 Gy, (95% CI) p-value 0 – 10053.2113-2.99 (-6.76; 4.65)> 0.5 0 – 12563.0132-1.63 (-4.82; 4.44)> 0.5 0 – 15071.41603.57 (-0.90; 12.3)0.143 0 – 20084.81801.81 (-1.24; 7.25)0.3 0 – 25098.21992.40 (-0.36; 7.18)0.1 0 – 300110.42184.05 (1.09; 9.16)0.003 0 – 500139.62535.15 (2.39; 9.73)< 0.001 0 – 1000172.32694.31 (2.16; 7.75)< 0.001 > 0189.42723.81 (1.81; 6.86)< 0.001 THYROID CANCER RISK AMONG CHILDREN AND ADOLESCENTS (BOTH SEXES) IN LOW-DOSE RANGE Cohort of children and adolescents: 97,191 persons 272 cases of thyroid cancer 272 cases of thyroid cancer

23. FITTED ATTRIBUTABLE RISK OF THYROID CANCER (BOTH SEXES) AS A FUNCTION OF AGE AT EXPOSURE Attributable risk Attributable risk = radiation-induced cases radiation-induced cases + spontaneous cases 100 % х 100 %

24. CONCLUSION Data on Chernobyl are useful for estimating long-term radiological effects following the accident at the Fukushima-1 NPP. Statistically significant SCREENING EFFECT on thyroid cancer incidence was detected in people lived in radioactively contaminated territories following the Chernobyl accident. The SCREENING EFFECT depends on calendar period of follow-up. The highest value of SIR (15.2 95% CI: 10.6; 20.9) was observed in the earliest follow-up period, from 1991 to 1995. Statistically significant radiation risk of thyroid cancer is for children and adolescents (0-17 years at the time of exposure) only. Statistically significant radiation risk of thyroid cancer is associated with thyroid doses > 250 mGy.