The thyroid gland is a small, butterfly-shaped organ at the base of the neck that produces hormones regulating metabolism. Thyroid cancer usually originates from follicular cells (papillary or follicular types), but a small percentage arises from C-cells (medullary carcinoma). The worldwide incidence of thyroid cancer has increased substantially over the past few decades, a trend only partially explained by improved detection. This global rise highlights the importance of identifying factors that increase the likelihood of developing the disease. This article explains the established and suspected risk factors for thyroid cancer.
Biological and Demographic Risk Factors
Non-modifiable, intrinsic characteristics are consistent risk factors for thyroid cancer. The most significant demographic difference is sex, as the disease occurs almost three times more often in women than in men. While the risk increases with age for both sexes, women are typically diagnosed younger, peaking in their 40s, while men are diagnosed in their 60s or 70s.
A personal history of benign thyroid diseases also elevates risk. Conditions such as goiter (an enlarged thyroid gland) or non-cancerous nodules are linked to a higher likelihood of malignancy. Hashimoto’s thyroiditis, an autoimmune condition causing chronic inflammation, is another factor that may increase risk due to ongoing cellular changes.
A general family history of thyroid cancer, not linked to a specific genetic syndrome, also increases overall risk. Having a first-degree relative (parent, sibling, or child) with the disease increases an individual’s risk. This non-syndromic familial pattern accounts for about 5% of papillary thyroid carcinoma cases, suggesting a hereditary predisposition that may involve multiple genes or shared environmental factors.
Environmental and Lifestyle Exposures
Exposure to ionizing radiation is the only established environmental cause of thyroid cancer. The risk is highest when exposure occurs during childhood or adolescence, as the young thyroid gland is sensitive to radiation’s carcinogenic effects. Historical sources include radiation therapy to the head and neck for benign conditions, and environmental exposure from nuclear accidents or fallout.
The radiation dose delivered and the age at exposure are the primary modifiers of this risk. The risk increases significantly after exposure to a mean dose exceeding 0.05 Gy to 0.1 Gy. Following exposure, there is a minimum latency period of five to ten years before cancer may appear.
The risk continues for decades, often peaking 20 to 30 years after the initial event. The majority of radiation-induced cases are the papillary type of thyroid carcinoma. This highlights the importance of long-term monitoring for individuals exposed to radiation in the neck region during youth.
Dietary iodine intake influences thyroid cancer risk, though the relationship is complex. Extreme iodine deficiency is associated with a higher incidence of follicular and the more aggressive anaplastic thyroid carcinoma. This is thought to be driven by chronic overstimulation of the thyroid gland by thyroid-stimulating hormone (TSH) attempting to compensate for the lack of iodine.
Conversely, excessive iodine intake has been associated with a rise in papillary thyroid carcinoma incidence following supplementation programs in some populations. While a correlation exists, a clear cause-and-effect relationship is not definitively established. The consensus supports continued iodine supplementation to prevent deficiency diseases while studying the effects of excessive intake.
Specific Inherited Genetic Syndromes
While most thyroid cancers are sporadic, a small portion is linked to highly penetrant, specific inherited genetic mutations. Medullary Thyroid Carcinoma (MTC), which arises from C-cells, is the type most commonly associated with inherited predisposition, accounting for about 25% of all MTC cases. These hereditary forms are caused by a germline mutation in the RET proto-oncogene.
The RET gene mutation is responsible for Multiple Endocrine Neoplasia type 2 (MEN 2), a hereditary cancer syndrome. MEN 2 is classified into two subtypes, MEN 2A and MEN 2B, both carrying a high risk of MTC. MEN 2B is the more aggressive variant, often resulting in MTC developing at a younger age.
Identifying a RET gene mutation allows for predictive genetic testing and proactive management, typically including prophylactic thyroidectomy to prevent MTC. Strong correlations exist between the specific RET mutation and the severity and age of disease onset.
Factors Under Ongoing Scientific Review
Certain factors are consistently associated with thyroid cancer in epidemiological studies, but evidence for a direct causal link is still under review. Obesity and metabolic syndrome, for instance, have been linked to an increased risk. Large analyses suggest that an increase in body mass index (BMI) is positively associated with a greater risk of thyroid cancer.
This association is hypothesized to involve biological mechanisms such as chronic low-grade inflammation, altered sex hormones, and insulin resistance, common in individuals with obesity. These metabolic changes may promote the growth of thyroid cancer cells. The link is complicated by the possibility of detection bias, where increased screening inadvertently discovers small tumors.
The higher incidence rate among women has led to research into the role of female hormonal factors. Researchers are investigating potential links between thyroid cancer risk and reproductive history, including oral contraceptives, hormone replacement therapy, and the number of pregnancies. While definitive causal proof is lacking, these areas remain a focus of study to understand the biological mechanisms behind the sex disparity.