Familial Risk Factors in Thyroid Cancer Across Generations and Geographics: A Systematic Review and Meta-Analysis

The increasing global incidence of thyroid cancer highlights the importance of accurately assessing risk factors, particularly those related to family history. Although having affected family members is widely recognized as a risk factor for thyroid cancer, the exact degree of risk and its variation across types of familial relationships, parental gender, and geographic regions remain unclear. This systematic review and meta-analysis aimed to clarify the association between family history and thyroid cancer risk. We conducted a comprehensive literature search of PubMed, Web of Science, and Embase following PRISMA guidelines, identifying 13 studies from 503 initially screened. Statistical analyses were performed using random-effects models to estimate pooled odds ratios and risk ratios, with subgroup analyses to assess variations across population and relationship types. Our findings showed an approximately 4.5-fold higher risk of thyroid cancer in individuals with affected family members. Individuals with affected siblings were more likely to develop thyroid cancer while the risks associated with maternal and paternal family history were comparable in magnitude, with no statistical difference between them. Socioeconomic, educational, and lifestyle differences did not significantly influence risk, and geographic variations in familial risk could not be statistically confirmed by the subgroup analysis, in the context of high between-study heterogeneity. These results suggest that family history is a substantial risk factor for thyroid cancer, reinforcing the need for enhanced surveillance and screening strategies for those with a familial predisposition.