Abstract

4053 Background: A recent study has reported the roles of Helicobacter pylori infection and germline variants in homologous-recombination (HR) gene as early onset of gastric cancer. However, the prognostic factors and genetic characteristics, especially about the variants in HR gene on the etiology of gastric cancer in younger and older patients, have not been clarified. Methods: We retrospectively analyzed the data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) utilization portal following its policy. Between June 2019 and August 2023, gastric cancer patients who conducted comprehensive cancer profile tests (Foundation One CDx, Foundation One Liquid, and OncoGuide NCC Oncopanel) were divided into patients aged ≤ 40 years (YGC) group and patients aged ≥ 70 years (EGC) group. The frequency of variants in HR gene ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, PALB2, RAD51C, RAD51D, RAD51, ATRX, ARID1A, BAP1, CDK12, MRE11, NBN, PTEN, FANCA, and FANCC), the incidence of microsatellite instability-high (MSI-H), the value of tumor mutation burden (TMB), and prognosis were compared between the two groups. Results: There were 81 patients in YGC group and 394 patients in EGC group. The proportion of female patients (63% vs. 25%, P< 0.01) and undifferentiated type cancer (60% vs. 27%, P< 0.01) were significantly higher in YGC group compared with those in EGC group. The frequency of variants in HR gene was higher in EGC group compared with that in YGC group (68% vs. 52%, P< 0.01). The incidence of MSI-H in YGC group was lower than that in EGC group (0% vs. 4.8%, P= 0.055), and the mean value of TMB in YGC group was significantly lower than that in EGC group as well (2.4mut/Mb vs. 7.0mut/Mb, P< 0.01). The median overall survival (OS) in YGC group was significantly shorter than that in EGC group (943 days vs. 1597 days, P < 0.01). Among EGC group, the median OS of patients with positivity of variants in HR gene was significantly longer than that of those without (1728 days vs. 1281 days, P < 0.05). On the other hand, the median OS was not significantly different between patients with positivity of variants in HR gene and those without in YGC group. Conclusions: In the present study, the YGC group had lower incidence of variants in HR gene and MSI-H, and lower value of TMB, compared with those in the EGC group. We estimate that the incidence of MSI-H and the value of TMB caused by the HR-deficiency, which may be linked with prognosis, differs according to the frequencies of the variants in HR gene or according to other factors, such as aging and lifestyle.