ABSTRACT
Beyond the few established hereditary cancer syndromes with an upper gastrointestinal cancer component, there is increasing recognition of the contribution of novel pathogenic germline variants (gPVs) to upper gastrointestinal carcinogenesis. The detection of gPVs has potential implications for novel treatment approaches of the index cancer patient as well as long-term implications for surveillance and risk-reducing measures for cancer survivors and far-reaching implications for the patients' family. With widespread availability of multigene panel testing, new associations may be identified with germline-somatic integration being critical to determining true causality of novel gPVs. Comprehensive cancer care should incorporate both somatic and germline testing.