PDF(Pubmed)
Abstract：
UNASSIGNED: Helicobacter pylori (H. pylori), a bacterium which chronically infects the stomach of approximately half the world\'s population, is a risk factor for the development of gastric cancer (GC). However, the underlying mechanism whereby H. pylori infection induces GC development remains unclear. Intermittent injection of the H. pylori cytotoxin-associated gene A antigen (CagA) protein into its host cell inhibits nuclear translocation of BRCA1/BRCA2, DNA repair proteins involved in the development of breast cancer/ovarian cancer. Interestingly, hereditary breast and ovarian cancer (HBOC) syndrome is associated with GC development. Here, we aimed to clarify the molecular link between H. pylori infection, BRCA1/2 pathogenic variants (PVs), GC and higher GC incidence in HBOC families.
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.
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.
摘要：
■幽门螺杆菌(H.pylori),一种慢性感染世界上大约一半人口的胃的细菌，是胃癌（GC）发展的危险因素。然而,幽门螺杆菌感染诱导GC发生的潜在机制尚不清楚.将幽门螺杆菌细胞毒素相关基因A抗原（CagA）蛋白间歇性注射到其宿主细胞中，可抑制BRCA1/BRCA2（参与乳腺癌/卵巢癌发展的DNA修复蛋白）的核易位。有趣的是,遗传性乳腺癌和卵巢癌（HBOC）综合征与GC的发展有关。这里,我们旨在阐明幽门螺杆菌感染之间的分子联系，BRCA1/2致病变种（PVs），HBOC家族中GC和较高的GC发病率。
■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.
■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.
