奥拉帕利加紫杉醇治疗与遗传性乳腺癌和卵巢癌(HBOC)家族史相关的遗传性胃癌患者的有效性和耐受性

Takuma Hayashi, Kenji Sano, Mako Okada, Manabu Muto, Ikuo Konishi
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摘要

幽门螺杆菌(H. pylori)是一种线虫,是全球慢性胃部感染的常见原因。2014 年,世界卫生组织(WHO)报告称,幽门螺杆菌感染是全球胃癌的主要病因(80%),并具有特定的致癌因素。在包括日本在内的东亚地区,98%以上的胃癌患者推测幽门螺杆菌感染是导致胃癌的原因。然而,只有某些类型的胃癌与幽门螺杆菌感染有关。以往的临床研究表明,幽门螺杆菌分泌的细胞毒素相关基因 A(CagA)抗原可抑制乳腺癌易感基因 1(BRCA1)或 BRCA2(一种修复受损 DNA 的因子)的核转位。因此,有人指出遗传性乳腺癌和卵巢癌(HBOC)与胃癌的发生有关联,但幽门螺杆菌感染导致胃癌发生的详细机制尚不清楚。通过癌症基因组医学建立的遗传性癌症信息库,我们的研究小组强调了 HBOC 家族中胃癌的高发病率,而且 HBOC 家族中的男性患者更易患胃癌。我们还验证了在遗传性胃癌患者中使用多聚 ADP 核糖聚合酶(PARP)抑制剂的安全性和有效性。本研究为指导检测出 BRCA1/2 基因突变的晚期/转移性胃癌患者确立早期治疗提供了大量证据。
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Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with hereditary gastric cancer linked to a family history of hereditary breast and ovarian cancer (HBOC)
Helicobacter pylori (H. pylori), a type of nematode, is a common cause of chronic stomach infection around the world. In 2014, the World Health Organization (WHO) reported that H. pylori infection is a leading cause of gastric cancer (80%) worldwide and has specific carcinogenic factors. H. pylori infection is presumed to be the cause of gastric cancer in more than 98% of gastric cancer patients in East Asia, including Japan. However, only some types of gastric cancers are associated with H. pylori infection. Previous clinical studies have revealed that the bacterium secretes the cytotoxin-associated gene A (CagA) antigen, which inhibits the nuclear translocation of breast cancer susceptibility gene 1 (BRCA1) or BRCA2, a factor that repairs damaged DNA. Accordingly, an association has been pointed out between hereditary breast and ovarian cancers (HBOC) and the development of gastric cancer; however, there is a lack of clarity about the detailed mechanisms underlying the development of gastric cancer by H. pylori infection. Using the information base on hereditary cancers built up through cancer genomic medicine, our group highlighted the higher incidence of gastric cancer in HBOC families, with a preponderance for gastric cancer in male patients from HBOC families. We also verified the safety and efficacy of using poly ADP-ribose polymerase (PARP) inhibitors in patients with hereditary gastric cancer. The present study offers substantial evidence for guiding the establishment of early treatment for patients with advanced/metastatic gastric cancer in whom BRCA1/2 mutations have been detected.
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