Risk Factors for Thyroid Cancer
Ionizing radiation exposure, particularly during childhood, is the only definitively established environmental risk factor for thyroid cancer, with genetic syndromes and demographic factors also playing significant roles. 1, 2, 3
Established Environmental Risk Factors
Ionizing Radiation Exposure
- Childhood radiation exposure is the single most important modifiable risk factor, with greater risk for papillary carcinoma in subjects exposed at younger ages 1, 3
- The risk increases after exposure to a mean dose of more than 0.05-0.1 Gy (50-100 mGy) 3
- Following the Chernobyl nuclear accident in 1986, there was an 80-fold increase in the incidence of thyroid tumors in children from affected regions 1
- The minimum latency period before the appearance of thyroid cancers after exposure is 5 to 10 years 3
- Risk is highest during childhood and decreases with increased age at exposure, being low in adults 3
- History of head and neck radiation exposure significantly increases malignancy risk and lowers the threshold for fine-needle aspiration 4, 5
Genetic and Familial Risk Factors
Hereditary Cancer Syndromes
- PTEN Hamartoma Tumor Syndrome (PHTS) carries substantial thyroid cancer risk, with epithelial differentiated thyroid cancer occurring in as many as one third of patients 6
- As many as 5% of individuals with PHTS under 20 years of age will develop differentiated thyroid cancer, with the youngest reported case occurring at 7 years of age 6, 1
- DICER1 syndrome confers a 16-24 fold increased risk for differentiated thyroid cancer, with cumulative incidence of multinodular goiter or thyroidectomy of 13% in males and 32% in females by 20 years of age 6
- Familial susceptibility factors exist for radiation-induced thyroid neoplasms, independent of other known risk factors 7
- Family history of thyroid cancer, particularly medullary thyroid carcinoma or familial syndromes, increases baseline malignancy probability 4, 5
Demographic and Biological Risk Factors
Race and Ethnicity
- Thyroid cancer incidence rates vary significantly by race and ethnicity 1
- Among women, papillary thyroid cancer rates are higher in Asians (10.96 per 100,000 woman-years) and lower in blacks (4.9 per 100,000 woman-years) 1
- Among men, papillary thyroid cancer rates are higher in whites (3.58 per 100,000 man-years) and lower in blacks (1.56 per 100,000 man-years) 1
Age and Gender
- Age less than 15 years or advanced age (>70 years) increases baseline malignancy probability 4, 5
- Male gender increases malignancy risk, as thyroid cancer is less common but more aggressive in men 4, 5
- Female sex is a known risk factor for developing thyroid neoplasms after radiation exposure 7
Additional Potential Risk Factors
Clinical and Environmental Factors
- Iodine intake (both deficiency and excess), TSH level, autoimmune thyroid disease, estrogen, obesity, lifestyle changes, and environmental pollutants have been investigated but not definitively established as risk factors 2, 8
- History of diseases associated with thyroid carcinoma may increase risk 5
- Genetic predisposition, hormonal and reproductive factors, and history of preexisting benign thyroid disease are potential risk factors requiring further investigation 8
Important Clinical Caveats
A critical pitfall is that most thyroid cancers present with normal thyroid function, so thyroid function tests (TSH, T3, T4) should not be relied upon for malignancy assessment 4
The dramatic increase in thyroid cancer incidence over recent decades may be partly attributable to increased detection of small papillary carcinomas due to improved diagnostic accuracy rather than a true increase in disease occurrence 1, 9
Undiscovered carcinogens, especially during intrauterine life or early childhood, and epigenetic changes may be responsible for increased thyroid cancer incidence, but more studies are necessary 2