1. Understanding 131Iodine Health Risks: Lessons from Chernobyl
NPHS 1530

2. Biological Incorporation of Iodine
131I is major fission product of uranium, thorium and plutonium
Concentrated by Thyroid
Beta radiation in thyroid
High levels kill tissue
Lower levels are carcinogenic
Uptake can be blocked by large doses of potassium iodide

3. 131I Exposure and Thyroid Cancer

4. 131I in Air at Chernobyl

5. 131I Ground Deposition: Chernobyl

6. Absorbed dose units
Quantity of energy imparted by radiation to a unit mass of matter such as tissue.
Absorbed dose is measured in grays (Gy), where 1 Gy equals 1 joule of energy absorbed per kilogram of matter.
One Gy produces a different intensity of biological effects on tissue depending on the type of radiation (alpha, beta, gamma, neutrons).
One milligray (mGy=10-3 Gy) is most common unit

7. 131I Decay Two stage decay Half life of 8.02 days
Beta emission with mm tissue penetration: I  β + e-antineutrino Xe*+ 606 keV
Gamma emission with less energy / penetration: Xe*  13154Xe + γ keV
Half life of 8.02 days

8. Isotope Half-Life
If t0 is time after generation of amount A with half life t½, the amount at time t-t0 is:
A(½) (t-t0)/t½
An alternate expression of this relationship:
Ae-(t-t0)/τ , where τ = t½/ln(2)
For 131Iodine, t½=8.02 days and τ =11.57 days

9. 131I Decay: Impulse (single short) exposure

10. 131I Decay: Impulse (single short) exposure

11. 131I Decay: Chernobyl 10 day profile

12. 131I Ground Deposition: Chernobyl

13. Acute Thyroid Levels of 131I in Children
Analytic Question 1: What is the scale for the thyroid doses?

14. Acute Thyroid Levels of 131I in Children
Analytic Question 1: What is the scale for the thyroid doses?
Roughly logarithmic. log10(0.5)=-1.3, log10(.1)=-1, log10(.3)=-0.52, log10(1)=0, log10(2)=1.3

15. Acute Thyroid Levels of 131I in Children
Analytic Question 2: Are the data nominal, ordinal, integer or ratio?

16. Acute Thyroid Levels of 131I in Children
Analytic Question 2: Are the data nominal, ordinal or integer or ratio?
Ordinal because they are ordered levels.

17. Acute Thyroid Levels of 131I in Children
Analytic Question 3: How do we test the hypothesis that the two dose distributions are different?

18. Acute Thyroid Levels of 131I in Children
Analytic Question 3: How do we test the hypothesis that the two dose distributions are different?
Chi-square test. They differ significantly because χ2 = , 5 d.f., p<0.001

19. Acute Thyroid Levels of 131I in Children
Analytic Question 3: How do we test the hypothesis that the two dose distributions are different?
Chi-square test. They differ significantly because χ2 = , 5 d.f., p< The difference is obvious when proportions plotted.

20. Acute Thyroid Levels of 131I in Children
Analytic Question 4: How do we test the hypothesis that there are differences in dosage by age group? Which groups appear to be different?

21. Acute Thyroid Levels of 131I in Children
Analytic Question 4: How do we test the hypothesis that there are differences in dosage by age group? Which groups appear to be different? In what way(s)?
Chi-square tests. They differ significantly because χ2 >10,000, 25 d.f., p< The <1 year group differs from all others; same for 1-3 year group. Note differences for high doses.

22. Acute Thyroid Levels of 131I in Children
Analytic Question 5: How do Mogilev and Gomel doses differ for (1) overall pattern and (2) age?

23. 131I Ground Deposition: Chernobyl

24. Acute Thyroid Levels of 131I in Children
Analytic Question 5: How do the Mogilev and Ukraine exposure distributions differ?

25. 131I Decay: Radiation After Impulse (single short) Exposure

26. 131I Cumulative Radiation in Thyroid

27. 131I Decay: Chernobyl 10 day profile

28. 131I Decay: Chernobyl 10 day profile

29. Acute Thyroid Levels of 131I in Children
Analytic Question 6: What might be factors underlying increased dose in young children in Gomel?

30. Biological Incorporation of Iodine
“The concentration of iodide in milk can be 20- to 30-fold higher than that found in maternal plasma (Brown-Grant K (1961) Extrathyroidal iodide concentrating mechanisms. Physiol Rev 41:189–213), matching the requirements of the suckling for the synthesis of thyroid hormones.”
Shennan & Peaker (2000) Transport of Milk Constituents by the Mammary Gland, Physiol Rev 80:

31. Biological Incorporation of Iodine
AT is total breast milk 131I activity ingested, V is infant feed volume, Γ1 is the feeding interval (t-t0). TE = 4.4 days.
Robinson PS, Barker P, Campbell A, Henson P, Surveyor I, Young PR. Iodine-131 in breast milk following therapy for thyroid carcinoma.
J Nucl Med. 1994;35:1797–1801

32. Biological Incorporation of Iodine
For maternal dose of 4000 MBq (bolus), need to wait days for safe breast-feeding.
Robinson PS, Barker P, Campbell A, Henson P, Surveyor I, Young PR. Iodine-131 in breast milk following therapy for thyroid carcinoma.
J Nucl Med. 1994;35:1797–1801

33. Biological Incorporation of Iodine
Consider for a single dose:
1-exp((-0.693*Γ1)/ TE) = 1-exp( Γ1 / 4.4 d )
Robinson PS, Barker P, Campbell A, Henson P, Surveyor I, Young PR. Iodine-131 in breast milk following therapy for thyroid carcinoma.
J Nucl Med. 1994;35:1797–1801

34. Biological Incorporation of Iodine

35. Acute Thyroid Levels of 131I in Children
Analytic Question 7: How do we quantify the relative risk of thyroid cancer relative to radioisotope exposures?

36. 131I Health Risk Assessment
Odds ratio: ratio of odds of an event in one group relative to another group
Definition:
Mogilev
Gomel
Thyroid cancer incidence in children under 15 years old in 1996 p1 p2

37. 131I Health Risk Assessment
Odds ratio: ratio of odds of an event in one group relative to another group
p1=15.9 X 10-6, q1=( X 10-6), p2=2.2X10-6, q2=1-(2.2X10-6)
Odds ratio is 7.23
Gomel
Mogilev
Thyroid cancer incidence in children under 15 years old in 1996
15.9 per 100,000
2.2 per 100,000

38. 131I Health Risk Assessment
Relative Risk (RR) = Odds ratio/(1-Rc+(Rc X OR)) where Rc is risk in control group
Odds ratio (OR) is 7.23, Rc = 10-7
Relative Risk =7.23/( *7.23)=7.23
Attributable Risk Percent= (RR-1)/RR=86.2% for the location of a person in Gomel vs. Mogilev
Gomel
Mogilev
Ukraine (pre)
Thyroid cancer incidence in children under 15 years old in 1996
15.9 /100,000
2.2 /100,000
0.1/100,000

39. 131I Health Risk Assessment
What is the Odds Ratio for pediatric thyroid cancer in Gomel versus Ukraine (pre-Chernobyl)?
p1=15.9 X 10-6, q1=( X 10-6), p2=10-7, q2=1-(10-7)
Odds Ratio = p1q2/p2q1 = 159
Gomel
Mogilev
Ukraine (pre)
Thyroid cancer incidence in children under 15 years old in 1996
15.9 /100,000
2.2 /100,000
0.1/100,000

40. 131I Health Risk Assessment: General Model
Possible factors in Thyroid Cancer Risk
Residence (e.g., Gomel vs. remainder of Belarus)
Age at exposure
Sex
Thyroid iodine dose (in Gray)
Pre-existing iodine status (e.g., deficiency)
Goiter and thyroid size as a proxy variables
Urinary iodine

41. 131I Health Risk Assessment: General Model

42. Zabloska et al. Brit J Cancer (2011) 104: 181-187
Modeled Excess Odds Ratio per Gray exposure (EOR/Gy) from screening of 11,970 individuals in Belarus exposed to Chernobyl 131I as children
Disease odds estimated as function of radiation dose, sex, age, proxy variables for iodine status (residence, goiter, thyroid size) and iodine dose

43. Zabloska et al. Brit J Cancer (2011) 104: 181-187
No significant increased incidence as a function of age at screening, residence at screening, urban/rural status, or urinary iodine concentration
Significant contributions of thyroid status proxy variables (history or diagnosis of goiter, family history of goiter)

44. Zabloska et al. Brit J Cancer (2011) 104: 181-187

45. Zabloska et al. Brit J Cancer (2011) 104: 181-187
What is the relationship?
How do we determine linear relationships?

46. Regression Analysis

47. Regression Analysis
Data relationships may be linear (single line) or non-linear (other function)
Use a least-squares criterion to fit the data to a model: y=f(x)+ε, where ε ~ N(0,σ) [Gaussian (bell-shaped) distribution with mean zero and unknown standard deviation σ)
Strategy: Minimize regression error, defined as the sum of the squared differences between an observation and the value predicted by the model.

48. Regression Analysis
Measure of goodness of fit is Pearson Product-Moment Correlation Coefficient: ratio of the covariance to the product of the standard deviations of the variables
r2 is the percentage of variance accounted for by the relationship

49. Regression Analysis
y= 2x ε, for gaussian ε with µ=0 and σ=4, 8, 16 or 32

50. Zabloska et al. Brit J Cancer (2011) 104: 181-187
2.15 EOR/Gy
r = 0.99 for estimates

51. Zabloska et al. Brit J Cancer (2011) 104: 181-187

52. 131I Health Risk Assessment: Lessons Learned for the Next Incident
Identifiable factors in Thyroid Cancer Risk
Thyroid iodine dose (in Gray)
Current Iodine status (e.g., deficiency)
Goiter and thyroid size as a proxy variables
Urinary iodine
Residence: Why do we have a Gomel vs. remainder of Belarus effect?
Suggestions?