Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

NCT01063517

Funding Statement

This clinical research was performed with research funding from the following: Japan Society for Promoting Science for TH (grant No. 19K09840), START-program Japan Science and Technology Agency (JST) for TH (grant No. STSC20001), and the National Hospital Organization Multicenter clinical study for TH (grant No. 2019-Cancer in general-02), and The Japan Agency for Medical Research and Development (AMED) (grant No. 22ym0126802j0001), Tokyo, Japan.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study complied with the principles of the Declaration of Helsinki and was approved by the Central Ethics Review Board of the National Hospital Organization Headquarters, Tokyo, Japan (approval number: NHO R4-04; dated: November 18, 2020) and the Kyoto University School of Medicine, Kyoto, Japan (approval number: M237; dated: August 24, 2022).

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AbbreviationsAEAdverse EventBRCAbreast cancer susceptibility geneCagACytotoxin-associated gene A antigenGCgastric cancerHBOChereditary breast and ovarian cancerH. pyloriHelicobacter pyloriHRDdeficiency of homologous recombinationOSover survivalPFSProgression Free SurvivalPARPpoly ADP-ribose polymeraseWHOWorld Health Organization