1. Thyroid Disease among A-bomb Survivors Exposed in Childhood Roy Shore, Kyoji Furukawa, Misa Imaizumi Radiation Effects Research Foundation shore@rerf.or.jp

2. Atomic Bomb Survivor Study Overview 2

3. A-bomb Study Characteristics Life Span Study  Includes >86,000 survivors of all ages at exposure, with estimated doses and long follow-up for mortality (1950- 2008) and cancer incidence (1958-2009)  Includes 13,000 exposed before age 5 and 9,500 at ages 5- 9, with a wide range of doses (1 mGy to >3 Gy) Adult Health Study (clinical examinations)  Includes >2,600 under 10 years of age, given ultrasound screening 3

4. Thyroid Weighted Absorbed Dose (mGy) Thyroid dose distribution among those <10 years old at exposure is similar to these. Proportion (%) 37,164 23,107 6,7536,1416,545 3,795 2,214 952 Life Span Study (LSS) Thyroid Dose Distribution 4

5. Thyroid Cancer Risk in the Life Span Study (LSS) 5

6. Weighted absorbed thyroid dose (Gy) (Modeled for age 10 at exposure and age 60 at risk) (Furukawa et al, Int J Cancer, 132:1222-26, 2013) Excess Relative Risk (ERR) 4 3 2 1 0 0.00.51.01.52.02.5 ERR Gy -1 = 1.28 (95%CI 0.6, 2.7) LSS Thyroid Cancer: Dose-response 6

7. Study ERR (95% CI) per Gy EAR (95% CI) per 10 4 PY Gy per 10 4 PY Gy LSS (Furukawa 2013) (est. for IR at age 10) 1.3 (0.6, 2.7)3.0 (1.4, 5.0) Rochester thymus x-ray (age 0; Adams 2010) 3.2 (1.5, 6.6)2.2 (1.4, 3.2) Israel tinea capitis x-ray (ages 0-15; Sadetzki 2006) 20.2 (12, 32)9.9 (5.7, 15) Michael Reese tonsils x-ray (ages 0-15; Ron 1995) 2.5 (0.6, 26)3.0 (0.5, 17) Childhood cancer RT (pooled; Veiga 2012) 1.3 (0.7, 2.3)N.A. Comparison of LSS Thyroid Cancer Risk with Other Studies of Childhood External Radiation Exposure 7

8. Comparison of LSS Thyroid Cancer Risk with Chernobyl Studies of 131 I ExposureStudy ERR (95% CI) per Gy EAR (95% CI) per 10 4 PY Gy LSS (Furukawa 2013) (est. for IR at age 10) 1.3 (0.6, 2.7)3.0 (1.4, 5.0) Ukraine (screening, exposure ages 0-17; Brenner 2011) 1.9 (0.4, 6.3)2.2 (0.04, 5.8) Belarus (screening, exposure ages 0-18; Zablotska 2011) 2.2 (0.8, 5.5)N.A. Ukraine & Belarus (Ecological, ages 0-18; Jacob 2006) 18.9 (11, 27)2.7 (2.2, 3.1) 8

9. (Adapted from: Furukawa et al, Int J Cancer, 132:122-26, 2013) Thyroid Cancer Risk by Age at Exposure and Attained Age 9

10. Thyroid Disease at Clinical Examination in the Adult Health Study (AHS) 10

11. Methods for Diagnosis of Thyroid Diseases  Thyroid examination at the routine AHS health examination  Questionnaire: previous thyroid diseases and treatments, family history, seaweed intake  Ultrasound examination (detected nodules ≧ 5mm)  Aspiration biopsy (solid nodules ≧ 10mm)  Blood tests Thyroid function : FT3, FT4, TSH Thyroid antibodies  Tumor information from Tumor Registries  Medical information (e.g. results of cytology, pathology) from hospitals (Imaizumi et al, 2013, unpublished) 11

12. 12 Radiation Dose and Solid Thyroid Nodules, AHS Screening 0 2 4 6 8 10 02413 Odds Ratio Thyroid weighted absorbed dose, Gy EOR/Gy= 2.0 (95%CI 1.3, 2.9), n=464 nodules (Imaizumi et al, JAMA, 295:1011-22, 2006)

13. 0 2 4 6 8 10 02413 0 2 4 6 8 02413 13 Odds Ratio Thyroid weighted absorbed dose, Gy EOR/Gy= 2.0 (95%CI 0.7, 4.9), n=70 cancers Odds Ratio Thyroid weighted absorbed dose, Gy EOR/Gy= 1.5 (95%CI 0.8, 2.7), n=156 nodules Radiation Dose, Thyroid Cancers and Benign Thyroid Nodules, AHS Screening Thyroid CancersBenign Nodules (Imaizumi et al, JAMA, 295:1011-22, 2006)

14. In Utero-exposed Clinical Cohort: Radiation Dose-response for Solid Thyroid Nodules 012 0 2 4 6 8 10 12 14 16 18 20 Odds Ratio Maternal Uterine Dose (Gy) Solid Nodules OR at 1 Gy = 2.78 (95% CI: 0.50, 11.8) P = 0.22 (Imaizumi et al, J Clin Endocrinol Metab. 2008;93:1641-8) 14

15. Summary of RERF Radiation and Thyroid Effects  Over the dose range 0-2 Gy, a linear model fits reasonably well.  Linear dose-response risk estimate is comparable to nearly all other studies of external irradiation and Chernobyl thyroid studies  For those with <100 mGy: Increased risk is uncertain, due to little risk and/or limited statistical power.  Those exposed at young ages are clearly at the highest thyroid cancer risk. Little risk is seen for those exposed as adults.  Thyroid cancer risk continues for >50 years after exposure.  Risk of benign solid thyroid nodules is increased by radiation  Probably a dose-related risk of thyroid nodules after in utero exposure, though this study lacked statistical power to fully determine 15