Endocrine Abstracts

Background: The incidence and mortality rates of thyroid cancer have shown a significant upward trend. However, the current understanding of risk factors associated with thyroid cancer remains ambiguous and inconclusive. This umbrella review aims to identify the relationships between non-genetic risk factors and thyroid cancer incidence, while also evaluating the quality and validity of existing evidence.

Methods: This umbrella review was performed according to the PRISMA guidelines. We performed a comprehensive search of PubMed, Embase and the Cochrane Database of Systematic Reviews to identify relevant meta-analyses or systematic reviews that explored non-genetic risk factors associated with thyroid cancer. We extracted the estimated summary effect and their 95% confidence intervals through fixed or random effects models of each meta-analysis. The methodological quality of the included meta-analyses was evaluated using the AMSTAR2 tool, while the quality of evidence was assessed using the GRADE framework. Furthermore, we conducted subgroup analyses by gender and performed sensitivity analyses to assess the robustness of the findings.

Results: We included 52 articles and identified 78 non-genetic risk factors with 109 associations, which belong to eight broad categories: dietary factors, behavioral factors, anthropometric indices, chemical exposure, radiation exposure, drug history, preexisting medical status and reproductive factors. Out of these associations, 66 were found to have a significant relationship with thyroid cancer risk. An increased risk of thyroid cancer was associated with excessive uptake of dietary nitrates and vitamin D, higher urinary iodine level, overweight, larger height, exposure to pesticides, diagnostic X-ray and I¹³¹, drug history with flavonoids and fertility drugs, reproductive factors including multiparity, history of hysterectomy, short pregnancy interval and older age at menopause, and medical conditions such as diabetes, breast cancer and organ transplantation. Whereas the uptake of dietary iodine and fish, tea, alcohol, smoke, weight loss, breastfeeding, oral contraceptive and pernicious anemia were identified to be inversely related to this risk. However, the majority of the included studies (65%) were categorized as “Critically Low” based on the AMSTAR2 assessment, and most of the evidence (86%) was of weak quality since the classification by GRADE was very low. Moreover, subgroup and sensitivity analyses showed that more risk factors were found in women, and most associations were consistent with the overall analysis.

Conclusion: Our findings indicate that several modifiable factors play essential roles in the primary prevention of thyroid cancer. However, the overall quality of evidence supporting these associations is currently limited. Future research, particularly well-conducted prospective studies with high quality, is necessary to determine causal relationships between these factors and thyroid cancer.