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Doses to most organs after exposure to diagnostic activities of 131I
are very low and, with the exception of the thyroid, not exceeding 10 mGy.
Most studies on cancer risk in populations examined with 131I
focus on thyroid cancer risk and leukemia. Holm et al. (1) followed 35,000
individuals given 131I for diagnostic purposes and 3,746 cancers
occurred more than 5 years after exposure. The overall standardized incidence
ratio (SIR) was 1.01 [95% confidence interval (CI)=0.98-1.04] (Table 1).
SIRs were significantly increased for endocrine tumors other than thyroid
(SIR=1.93) and lymphomas (SIR=1.24). Both sites showed a decreasing trend
with time after exposure arguing against a radiation effect. For the sites
receiving higher doses of 131I, i.e. bladder and stomach, no
increased risks were noted (Table 1).
| Table 1: |
Relative risk of cancer in specific sites in relation to
reason for iodine-131 exposure and number of patients in each study |
| |
|
Cancer site |
| Reason for exposure |
No. of patients
(Ref. No)
|
Stomach |
Breast |
Bladder |
Kidney |
Thyroid |
Leukaemia |
All |
| Diagnostic procedures |
35,074 (5) |
1.0 (a)
(960) |
1.0
(739) |
1.1 (b)
(259) |
-
- |
- |
- |
1.0
(3,746) |
|
36,326 (6) |
- |
- |
- |
- |
- |
1.2
(152) |
- |
|
34,104 |
- |
- |
- |
- |
0.75 (e)
(25) |
- |
- |
| Treatment for hyperthyroidism |
1,005 (23) |
0.6 * (c) |
0.7
(23) |
1.2 (b)
(7) |
- |
3.8
(3) |
1.2
(4) |
0.8
(105) |
|
18,379 (21) |
- |
- |
- |
- |
0.8 (d)
(17) |
- |
- |
|
10,552 (24) |
1.05
(92) |
1.02
(169) |
1.12 (b)
(51) |
1.39 *
(66) |
1.29
(18) |
0.94
(34) |
1.06 *
(1,543) |
| Treatment for thyroid cancer |
194 (31) |
- |
- |
- |
- |
- |
20.6
(2) |
- |
|
258 (32) |
0.91
(1) |
2.37 *
(6) |
6,52 *
(3) |
- |
- |
12.00 *
(3) |
1.51 *
(20) |
|
298 (33) |
1.7
(1) |
1.9
(5) |
8.8 *
(7) |
- |
- |
6.25 *
(3) |
1.94 *
(33) |
|
834 (34) |
1.75
(5) |
0.74
(9) |
1.61
(4) |
3.00 *
(7) |
- |
2.44
(4) |
1.43 *
(99)
|
(a) Number of cases shown in parenthesis
(b) No distinction between bladder and kidney
(c) All digestive organs included.
(d) Figures showing iodine 131 treated compared to surgically treated
patients.
(e) Excluding those referred under the suspicion of a thyroid tumor.
* Significantly different from unity. |
Leukemia risk was studied in the same cohort and 152 leukemias were
found giving a SIR of 1.16 (95% CI 0.98-1.36) (2). The risk for leukemia
was similar for chronic lymphatic leukemia (CLL) (SIR=1.14) and non-CLL
(SIR=1.17) and since CLL is a entity not found to be associated with ionizing
radiation it was concluded that the increased risk was not caused by 131I
exposure. The individuals in the cohort have now been followed for an average
of 24 years and individual doses were recently calculated for the first
time using administered activity of 131I, 24-hour thyroid uptake
and data from ICRP tables (3,4). The mean thyroid uptake was 40%, the mean
administered amount of 131I, 1.9 Mbq, giving a mean thyroid
dose of 1.1 Gy. The overall SIR was 1.35 (95% CI 1.05-1.71; Table 2) and
the total number of thyroid cancers 67. In order to address the possibility
of the underlying cause of examination influencing risk, the patients were
divided into those referred under the suspicion of a thyroid tumor (n=10,785)
and those referred for other reasons (n=23,319). The SIRs were 2.86 (95%
CI 2.06-3.86) and 0.75 (95% 0.48-1.10), respectively (Table 2). A total
of 3 thyroid cancers among those younger than 20 years at exposure was
found giving a non-significant SIR of 1.69. Thyroid nodularity was analyzed
in a supcohort of these patients and 1,005 131 I exposed women
were compared to 248 controls. The incidence of nodules in the two groups
were similar (10.6% and 11.7%, respectively), but when risk was related
to dose a positive dose-response relationship was found (5).
| Table 2: |
Observed number of cases (Obs.), thyroid cancer risk (SIR),
and 95% confidence interval(CI) in relation to estimated thyroid dose and years after
iodine 131 administration. The first 5 years after exposure were excluded. |
| Years after 131I administration |
|
5-9 |
10-19 |
>= 20 |
All |
| Dose, Gy |
Obs. |
SIR |
95% CI |
|
Obs. |
SIR |
95% CI |
|
Obs. |
SIR |
95% CI |
|
Obs. |
SIR |
95% CI |
| All |
| <= 0.25 |
4 |
1.72 |
0.47-4.40 |
|
4 |
0.77 |
0.21-1.97 |
|
3 |
0.93 |
0.19-2.73 |
|
11 |
1.03 |
0.51-1.83 |
| 0.26-0.50 |
5 |
2.67 |
0.87-6.24 |
|
6 |
1.41 |
0.52-3.07 |
|
5 |
1.93 |
0.63-4.51 |
|
16 |
1.84 |
1.05-2.98 |
| 0.51-1.00 |
1 |
0.50 |
0.01-2.77 |
|
4 |
0.86 |
0.23-2.20 |
|
4 |
0.95 |
0.26-2.44 |
|
9 |
0.46 |
0.38-1.57 |
| >1.00 |
11 |
2.95 |
1.47-5.28 |
|
8 |
0.93 |
0.40-1.84 |
|
12 |
1.70 |
0.88-2.98 |
|
31 |
1.60 |
1.09-2.27 |
| All |
21 |
2.11 |
1.31-3.23 |
|
22 |
0.97 |
0.61-1.47 |
|
24 |
1.41 |
0.90-2.10 |
|
67 |
1.35 |
1.05-1.71 |
|
|
|
|
| Referred for suspicion of a thyroid tumor |
| <= 0.25 |
2 |
4.88 |
0.59-17.62 |
|
2 |
2.17 |
0.26-7.85 |
|
2 |
5.71 |
0.69-20.64 |
|
6 |
3.57 |
1.31-7.77 |
| 0.26-0.50 |
5 |
7.94 |
2.48-18.52 |
|
4 |
2.78 |
0.76-7.11 |
|
2 |
5.71 |
0.69-12.18 |
|
12 |
4.30 |
2.22-7.51 |
| 0.51-1.00 |
0 |
0.00 |
0.00-6.15 |
|
3 |
2.14 |
0.44-6.26 |
|
1 |
1.14 |
0.03-6.33 |
|
4 |
1.39 |
0.38-3.56 |
| >1.00 |
7 |
3.87 |
1.55-7.97 |
|
6 |
2.17 |
0.79-4.71 |
|
7 |
2.53 |
1.02-5.21 |
|
20 |
2.72 |
1.66-4.20 |
| All |
14 |
4.06 |
2.22-6.81 |
|
15 |
2.30 |
1.29-3.79 |
|
13 |
2.75 |
1.47-4.71 |
|
42 |
2.86 |
2.06-3.86 |
|
|
|
|
| Referred for other reasons |
| <= 0.25 |
2 |
1.04 |
0.13-3.76 |
|
2 |
0.47 |
0.06-1.69 |
|
1 |
0.35 |
0.01-1.95 |
|
5 |
0.55 |
0.18-1.29 |
| 0.26-0.50 |
0 |
0.00 |
0.00-2.97 |
|
2 |
0.71 |
0.09-2.57 |
|
2 |
1.07 |
0.13-3.86 |
|
4 |
0.68 |
0.18-1.73 |
| 0.51-1.00 |
1 |
0.71 |
0.02-3.95 |
|
1 |
0.31 |
0.01-1.71 |
|
3 |
0.90 |
0.19-2.64 |
|
5 |
0.47 |
0.20-1.46 |
| >1.00 |
4 |
2.08 |
0.57-5.33 |
|
2 |
0.46 |
0.06-1.65 |
|
5 |
1.17 |
0.38-2.73 |
|
11 |
1.04 |
0.52-1.86 |
| All |
7 |
1.08 |
0.43-2.22 |
|
7 |
0.48 |
0.19-0.98 |
|
11 |
0.89 |
0.45-1.60 |
|
25 |
0.75 |
0.48-1.10 |
Ionizing radiation is still the only established etiological factor
for thyroid cancer in humans (6) and the thyroid gland is one of the most
radiosensitive organs in the body (7,8). Most of our knowledge on radiation
induced thyroid cancer derives from studies of the A-bomb survivors (8,9)
and of patients exposed to external radiotherapy (10-13). Not very many
studies of thyroid cancer risks after diagnostic X-ray examinations have
been performed but one of the major shows no increased risk (14).
In a pooled analyses of seven studies by Ron et al. (12) it was concluded
that one of the most remarkable features of thyroid cancer was that it
is induced by low doses, i.e. 0.10 Gy, of brief external gamma radiation
in childhood, but rarely develops after adult exposure. The study included
58,000 exposed and 61,000 non-exposed children developing a total of 700
thyroid cancers and a decreasing risk with increasing age at exposure was
seen even within the limited age range.
In a study of children, given external radiotherapy before the age of
1year for a supposed enlarged thymus, including 2,856 cases and 5,053 controls,
a total of 43 thyroid cancers were found giving a more than 10-fold increased
risk in the exposed compared to the unexposed group (15).
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