**4. Conclusion**

Despite the solid evidence for heritability of thyroid cancer, only a handful of variants have been significantly associated with an increased risk of DTC representing the most common form of thyroid cancer. The high heritability of the disease is likely due to the contribution of rare high-penetrance variants in some cases and the combination of common low-penetrance variants in others, as well as the influence of common shared environmental factors in DTC-prone families or in specific groups of the general population. So far, efforts to identify DTC predisposing genes outside of syndromic FNMTC led to the identification of mainly low-to-moderate penetrance genes, and routine genetic testing for these genes is not recommended. Further large studies to characterize their penetrance and function and to identify new DTC-associated loci or alternative hereditary mechanisms such as epigenetic modifications are required to improve our understanding of DTC tumorigenesis. Ultimately, risk prediction models integrating family history of DTC, PRS, and some modifiable risk factors (obesity, exposure to ionizing radiations from medical diagnostic procedure, etc.) may help stratify individuals according to their risk of developing DTC, which can be useful for elaborating screening policies. Moreover, inherited genetic factors can also impact the final outcome of the disease such as histological subtypes, localization of metastases, or molecular profiling of the tumor, and their characterization can help to predict effectiveness of the initial treatment [120].
