Gastric cancer (GC) has long been a ‘Cinderella’ among hereditary cancers. Until recently, single-gene testing (SGT) was the only approach to identify high-risk individuals. With the spread of multigene panel testing (MGPT), a debate arose on the involvement of other genes, particularly those pertaining to homologous recombination (HR) repair. We report our mono-institutional experience in genetic counseling and SGT for 54 GC patients, with the detection of nine pathogenic variants (PVs) (9/54:16.7%). Seven out of fifty (14%) patients who underwent SGT for unknown mutations were carriers of a PV in CDH1 (n = 3), BRCA2 (n = 2), BRCA1 (n = 1), and MSH2 (n = 1), while one patient (2%) carried two variants of unknown significance (VUSs). CDH1 and MSH2 emerged as genes involved in early-onset diffuse and later-onset intestinal GCs, respectively. We additionally conducted MGPT on 37 patients, identifying five PVs (13.5%), including three (3/5:60%) in an HR gene (BRCA2, ATM, RAD51D) and at least one VUS in 13 patients (35.1%). Comparing PV carriers and non-carriers, we observed a statistically significant difference in PVs between patients with and without family history of GC (p-value: 0.045) or Lynch-related tumors (p-value: 0.036). Genetic counseling remains central to GC risk assessment. MGPT appeared advantageous in patients with unspecific phenotypes, although it led to challenging results.

The present work aims to link the redox and cell-centric theories of chronic processes in human biology, focusing on ageing. A synthetic overview of cellular redox pathways will be integrated by the concept of hormesis, which disruption leads to several physiopathological processes. The onset of age-related diseases due to the restriction of homeodynamic capacity will be herein considered in a redox fashion. Up-to-date arguments on hormetic agents, such as geroprotectors, dietary interventions, and physical exercise are refining the presented theoretical framework, integrated by insights from extracellular vesicles, microbiota, pollutants, and timing mechanisms. The broad concepts of exposome encompass the redox-based alteration of cellular hormesis for providing meaningful perspectives on redox biogerontology.