Expression of DNA Damage Response Markers in Early-Onset or Familial Gastric Cancers

Background: Early-onset or familial gastric cancer (GC) is known to have clinicopathologic profiles different fromthose of sporadic GC. We aimed to compare DNA damage response marker expression between early-onset or familialGC and sporadic GC. Methods: GC samples were obtained from patients who underwent gastrectomy for GC at SeoulNational University Hospital. Immunohistochemical analyses of various DNA damage response markers, includingBRCA1, BRCA2, MRE11, RAD51C, and γH2AX, were performed using 54 early-onset GC, 59 familial GC, and 337sporadic GC tissue microarray samples. Correlations between marker expression and clinicopathologic features wereevaluated by univariate and multivariate analyses, and overall survival was analyzed. Results: The rate of γH2AXpositivity was significantly higher (p < 0.001) in early-onset or familial GC than in sporadic GC. In contrast, the rates ofMRE11 negativity and RAD51C negativity were significantly higher in sporadic GC than in early-onset or familial GC.BRCA1 negativity was associated with decreased overall survival in sporadic GC (p = 0.002), and MRE11 negativitywas associated with decreased overall survival in sporadic GC (p = 0.012). Conclusion: Our results show significantdifferences in DNA damage response marker expression between early-onset or familial GC and sporadic GC.