SMAD4 and gastric cancer: Previous studies have shown that individuals with SMAD4 pathogenic mutation may have an increased risk of severe gastric polyposis [9, 17] and a higher risk for gastric cancer [18]; most JPS patients with a SMAD4 pathogenic mutations may have hereditary hemorrhagic telangiectasia (HHT) [19–21]; and people with either an SMAD4 or BMPR1A pathogenic variant are more likely than those without a pathogenic variant identified to have more than ten lower GI polyps and a family history of GI cancer [6, 17, 22, 23].