Pathogenesis

Radiation

The major known risk factor for DTC is prior exposure to radiation. A history of radiation exposure has two major clinical implications: (i) increased risk of developing thyroid nodules and (ii) increased risk of a thyroid nodule being malignant.

Risk factors associated with radiation-induced thyroid tumors:

• Amount of radiation exposure

• Young age at exposure to radiation

• High serum Tg concentration

• Other radiation-related tumors

• First-degree relative with radiation-related tumor.

The most significant sources of radiation exposure are therapeutic irradiation and environment disasters. Radiation is known to induce DNA strand breaks (23,24). Recently, an increased incidence of childhood thyroid cancer was observed in heavily contaminated territories after the Chernobyl accident. Children aged less than five years at the time of the accident were more likely to develop thyroid cancer (25).

Studies of adult iodine-131 (I-131) exposure for therapeutic and diagnostic purposes continue to be reassuring with respect to addition of radiation risks. However, there is a suggestion of a small effect of I-131 on increased thyroid nodularity, carcinoma incidence, and thyroid carcinoma mortality, although this increased thyroid condition could be also related to the underlying thyroid condition or an increase in surveillance or diagnosis (26).

Oncogenes

The most frequent genetic alterations in DTC are somatic rearrangements of the RET proto-oncogene, which generate several chimeric RET\PTC in PTC.

Pre-existing Thyroid Disease

Thyroid carcinoma is often preceded by other thyroid diseases. Goiter, benign thyroid nodules, lymphocytic thyroiditis, and Graves' disease, all are common processes. Whether patients with these abnormalities are at higher risk for developing thyroid carcinoma is uncertain (27,28).

Hormonal and Reproductive Factors

Thyroid carcinoma, like most thyroid diseases, occurs more frequently in women than in men, suggesting that hormonal factors are involved in its pathogenesis. More studies need to be performed to conclude if puberty, parity, or exogenous estrogens are associated with thyroid cancer.

Dietary Factors

Iodine: Some decades ago, a study showed the relationship between iodine-deficient endemic goiter and thyroid carcinoma (29). Since then, other studies demonstrated that iodine supplementation failed to reduce the incidence of thyroid cancer (30-32). However, the effects of iodine intake on development of specific histologic types of thyroid carcinoma are clearer. In endemic goiter areas, follicular and anaplastic carcinomas predominate. In areas with iodine supplementation, the proportion of follicular carcinoma declines and that of PTC increases (33,34). The role of other dietary factors on DTC pathogenesis remains very controversial.

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