Highly cited foundational work, such as the 2000 Gastroenterology study by Giardiello et al. (Giardiello et al., 2000), which highlighted the significantly elevated cancer risk in familial PJS, and the 2012 Clinical Cancer Research paper by Tan et al. (Tan et al., 2012), which quantified the lifetime cancer risks associated with germline PTEN mutations, has laid the groundwork for understanding the hereditary cancer predispositions in PJS (Fig. 3C). This evidence concerns the gene PTEN and Peutz-Jeghers syndrome.