UNASSIGNED: We retrospectively reviewed data from Japanese patients undergoing precision treatment using cancer genomic medicine.
UNASSIGNED: We found a higher GC incidence in HBOC families having germline pathogenic variants (GPVs) of BRCA1/2 (2.95% vs. 0.78% in non-HBOC families). Next, we found that 96.1% of H. pylori-infected patients received cancer genomic medicine for advanced GC, and > 16% advanced GC patients had gBRCA2 PVs. Furthermore, expressing wild-type BRCA1/2 in Gan mice (a mouse model of human GC) inhibited GC development. Thus, gBRAC1/2 PVs and H. pylori infection synergistically increase the risk of GC development.
UNASSIGNED: Our study highlights the need to investigate the potential of therapeutic agents against BRCA1/2 PVs to avoid the development of GC in HBOC families. In addition, our results suggest that poly (ADP-ribose) polymerase (PARP) inhibitors could potentially inhibit GC development and progression with gBRCA1/2 PVs.
■我们回顾了使用癌症基因组医学进行精准治疗的日本患者的数据。
■我们发现在具有BRCA1/2种系致病变异体(GPV)的HBOC家族中GC发病率较高(2.95%vs.非HBOC家族中的0.78%)。接下来,我们发现96.1%的幽门螺杆菌感染患者接受晚期GC的癌症基因组药物治疗,>16%的晚期GC患者有gBRCA2PV。此外,在Gan小鼠(人GC的小鼠模型)中表达野生型BRCA1/2抑制GC发展。因此,gBRAC1/2PV和幽门螺杆菌感染协同增加GC发展的风险。
■我们的研究强调需要研究针对BRCA1/2PV的治疗药物的潜力,以避免在HBOC家族中发展GC。此外,我们的结果表明,聚(ADP-核糖)聚合酶(PARP)抑制剂可能潜在地抑制gBRCA1/2PV的GC发展和进展.