Nongenetic risk factors for thyroid cancer: an umbrella review of evidence

Background: The incidence of thyroid cancer has increased annually, but the risk factors for thyroid cancer are still unclear. In this umbrella review, we aimed to identify associations between nongenetic risk factors and thyroid cancer incidence, and assess the quality and validity of the evidence.

Methods: PubMed, Embase and the Cochrane Database of Systematic Reviews were searched to identify related meta-analyses or systematic reviews of epidemiological studies. We extracted the estimated summary effect and 95% confidence interval (CI) through fixed or random effects models of each meta-analysis. AMSTAR2 and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) were used to evaluate the methodological quality of the included meta-analyses and the quality of evidence respectively. Further subgroup analyses by sex and sensitivity analyses were conducted.

Results: We identified 53 articles with 112 associations, of which 69 had significant relationships with thyroid cancer risk, including factors related to iodine, nitrates, fish, vitamin D, tea, alcohol, smoke, body mass index (BMI), pesticides, X-ray, I¹³¹, oral contraceptives, flavonoids, reproductive factors and some medical conditions. However, most studies (65%) were categorized as "critically low" on the basis of AMSTAR2, and most evidence (86%) was of weak quality since the classification by GRADE was very low. Moreover, subgroup and sensitivity analyses revealed more risk factors in women than in men.

Conclusion: We found that several modifiable factors have essential effects in the primary prevention of thyroid cancer, but few high-quality studies exist. In the future, more well-conducted, especially prospective, studies are needed to confirm the results.

Trial registration: The protocol for this review was registered in PROSPERO (CRD42022352841).