The changing incidence of thyroid carcinoma in Shenyang, China before and after universal salt iodization

Background

Thyroid carcinoma (TC) is the most commonly encountered endocrine malignancy. Its incidence is increasing over the years, and constitutes approximately 1% of all the new diagnoses of cancer each year in the United States.

The etiology of TC is multifactorial; both genetic and environmental factors play key roles in modulating TC pathogenesis [1]. A clear relationship between iodine supply to the population and TC incidence has not been proven and is still debated [2]. However, the distribution of TC types (the higher prevalence of PTC in comparison to FTC) is related to higher iodine intake [3].

Universal salt iodization (USI) has been carried out throughout China since 1996, and as a result, iodine intake has increased countrywide. Meanwhile, an increase in the prevalence of thyroid disease has been found with increasing iodine intake [4].

To further investigate the association between iodine intake and risk for TC, we compared the detection rates of TC after USI with the rates before USI in the First Hospital of China Medical University in Shenyang, a city of Northeastern China, which was previously an iodine deficient area.

Material and Methods

STATISTICAL ANALYSIS:

All statistical analyses were conducted by using the statistical program SPSS 16.0 for windows (SPSS, Chicago, IL, USA). Data were analyzed using the Student’s t test or t’ test for continuous variables, and the χ² test for nonparametric data. Numerical data are presented as mean ±SD, where appropriate. A P value below 0.05 was considered statistically significant.

Results

THE DETECTION RATES OF TC BEFORE AND AFTER USI:

The total detection rate of TC after USI (1.31%, 1154/87911) was significantly higher than before USI (0.71%, 85/11903) (χ²=30.64, P<0.001). As to each histological type of TC, the detection rate of PTC (1.15%, 1009/87911) after USI was significantly higher than before USI (0.44%, 52/11903) (χ²=50.38, P<0.001), and that of MTC after USI (0.05%, 44/87911) was also higher than before USI (0.01%, 1/11903) (χ²=4.04, P<0.05), while that of FTC after USI (0.05%, 46/87911) was significantly lower than before USI (0.18%, 22/11903) (χ²=27.04, P<0.001) and that of UTC showed no significant difference after USI compared with before USI (P>0.05).

THE CONSTITUENT RATIOS OF TC BEFORE AND AFTER USI:

The constituent ratio of PTC after USI was significantly higher than before USI (87.44% vs. 61.18%, χ²=44.37, P<0.001), while that of FTC was significantly lower than before USI (3.99% vs. 25.88%, χ²c=69.02, P<0.001), that of UTC was lower than before USI (2.08% vs. 7.06%, χ²c=6.33, P<0.05), and that of MTC showed no significant difference after USI compared with before USI (P>0.05).

SEX DISTRIBUTION IN TC BEFORE AND AFTER USI:

Except for MTC, the detection rates of female patients with PTC, FTC, and UTC were all higher than in male patients before and after USI. However, the female/male ratio of each histological type of TC showed no significant difference before and after USI (P>0.05) (Table 1.)

MEAN AGE DISTRIBUTION IN TC BEFORE AND AFTER USI:

The mean age of the patients with TC after USI was lower than before USI (t’=2.48, P<0.05), that of female patients after USI was lower than before USI (t’=2.10, P<0.05), but that of male patients showed no significant difference before and after USI (t=1.43, P>0.05). The mean ages of both female and male patients with each histological type of TC showed no significant difference before and after USI (P>0.05) (Table 2.)

THE INCIDENCES OF TC COMPLICATED WITH OTHER THYROID DISEASES BEFORE AND AFTER USI:

The incidence of PTC complicated with nodular goier after USI was significantly higher than before USI (χ2=34.28, P<0.001) and that of PTC complicated with chronic lymhocytic thyroiditis was also higher than before USI (χ2c=4.59, P<0.05), while that of each histological type of TC complicated with thyroid adenoma showed no significant difference before and after USI (P>0.05) (Table 3.)

Discussion

In the present investigation we noted a significant rise in the total incidence of TC after USI, which largely resulted from an increasing incidence of PTC. Whether the total incidence of TC is influenced by iodine intake is still controversial. In Italy, the incidence of TC was higher in an iodine-deficient area compared to that in an iodine-sufficient region [5]. In China, the prevalence and incidence of TC in iodine-excessive areas were much higher than those in the other 2 iodine-deficient and iodine-sufficient areas [6]. Moreover, some of the highest incidence rates of TC were found in Iceland and Hawaii, both known to have long-standing high iodine intake, although exposure to volcanic activity (and natural radiation) has been suggested as an explanation for the high incidence in these 2 areas [7,8]. However, several other countries [Tyrol (Austria), lower Franconia (Germany), Geneva (Switzerland), Sweden and Salta (Argentina)] introducing iodinated salt programs have observed increasing trends in PTC [9]. Effective iodine prophylaxis programs also lead to a decrease in the frequency of MTC, as well as its more malignant counterpart, FTC [10]. The incidence of ATC decreased after higher iodination of salt [11].

There are many problems in assessing possible changes in TC incidence rates in relation to iodine intake. Factors such as screening programs, clinical practice, and pathological criteria, may show significant variations with time, particularly in iodine-deficient areas before and after USI. Indeed, the change in the incidence of TC after USI is the combined result of multiple factors and it is unlikely that a certain single factor accounts for this result completely. Fortunately, the majority of increased TC was PTC with good prognosis, a striking proportion of which were microcarcinoma. As a result, despite the incidence of TC increasing significantly, the mortality remained stable in recent years [12].

Available evidence from animal experiments and epidemiological studies, as well as from the introduction of iodine prophylaxis, has demonstrated a relationship between iodine intake and the types of thyroid carcinoma [2,13–22]. Consistent with the literature, our results showed there was a change in the distribution of its main histological subtypes of TC, especially the ratio of PTC to FTC after USI. Animal experiments suggested that iodine deficiency and iodine excess could induce carcinomas derived from thyroid follicular cells through different mechanisms (Table 4). A clear increase in the incidence of thyroid epithelial cell carcinomas after prolonged iodine deficiency leading to a situation of the thyroid gland by thyrotropin and possibly other growth factors was observed in the iodine-deficient animals where the malignancies reported were FTC and PTC, whereas the mechanism in which iodine excess-induced TC is still not clear. Only PTC was found in experimental animals fed with an iodine-adequate and iodine-rich diet [2,13].Clinical studies revealed that high iodine intake seemed to be a significant risk factor for the occurrence of BRAF mutation, which occurred uniquely in PTC among various TC and was most important for the initiation of PTC among genetic alterations. The increased PTC incidence may result from BRAF mutation induced by high iodine intake, which may therefore be a risk factor for the development of PTC [23–25]. It has also been suggested that iodine can prevent the progression of differentiated thyroid carcinoma to anaplastic carcinoma by interfering with oncogene expression or the mutation of tumor suppressor genes such as BRAF, ERK, RAS, and p53 [26,27].

In the present study neither increased nor decreased female/male ratio of the patients with TC was found with increasing iodine intake, although the female/male ratio of each histological type of TC changed slightly before and after USI, demonstrating increasing iodine intake did not influence the female/male ratio of the patients with TC, consistent with the result of Cui et al. [22]. A shift to younger age with female incidence was also noted in the present study and may relate to the contributions of estrogen to the development of TC.

Our results showed that the incidence of PTC complicated with nodular goiter increased after USI, indicating iodine may be a risk factor for a shift from nodular goiter to TC, especially to PTC. In addition, a high dietary intake of iodine may be associated with a high frequency of PTC and thyroiditis; thyroiditis is more commonly associated with PTC than with other types of TC [28]. Our results showed that the incidence of PTC complicated with chronic lymphocytic thyroiditis increased after USI.

Conclusions

In conclusion, the detection rate of TC increased significantly, PTC predominated in the histological types of TC, and the mean age of female patients with TC decreased after USI. The patients with either nodular goiter or chronic lymphocytic thyroiditis under high iodine intake should be followed up.