Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10⁻⁸), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10⁻⁹), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

Mycoplasma pneumoniae is one of the causative organisms of community-acquired pneumonia which is found commonly in younger patients. Extrapulmonary complications similar to autoimmune disease are caused by M. pneumoniae following the initial infection. The mechanism and pathology of onset is not clear, but it is considered that excessive host immunoreactions play a part in the onset of mycoplasmal pneumonia and its extrapulmonary complications. In this study, we investigated the participation of the immune response, excluding the participation of Th1 and Th2 which has previously been investigated. In this study, the host immune response of an antigen induced inflammation model using SPF mice repeatedly sensitized with M. pneumoniae antigens was analyzed. The specificity of M. pneumoniae antigens in the Th17 response of murine lymphocytes in vitro was also examined. Frequent and concentrated sensitization induced exacerbation of lung inflammation immunologically and pathologically, and evoked intrapulmonary IL-17A and IL-10 production. M. pneumoniae antigen stimulation induced proliferation of mouse lymphocytes and caused production of IL-17A and IL-10. In addition, it was shown that IL-17A and IL-10 production was increased in the presence of IL-6 and TGF-β1. It was shown that M. pneumoniae antigens induced potent immunoreaction and enhanced the Th17 cell response both in vivo and in vitro, and that both Treg and IL-10 are involved in the suppression of IL-17A production. This raises the possibility that breakdown of the immune balance may be part of the process leading to subsequent development of extrapulmonary mycoplasmal pneumonia.

Significance: This study directly demonstrates virulence-associated features ofHelicobacter suisinfection using isolates obtained from human stomachs.H. suisis the second-most-prevalentHelicobacterspecies in the human stomach, but diagnostic tests forHelicobacter pylorioften fail to diagnoseH. suis. H. suisdoes not have orthologs of either cytotoxin-associated gene A (CagA) or vacuolating cytotoxin A (VacA), two major virulence factors inH. pylori, suggesting that the molecular pathogenicity ofH. suisand clinical manifestations caused byH. suisinfection are different from those caused byH. pylori. This study paves the way for epidemiological research aimed at identifying the causal relationships betweenH. suisand gastric diseases and developing diagnostic methods.

This study used multilocus sequence typing (MLST) of total DNA extracted from faecal specimens to genotype Helicobacter pylori to analyse intra-familial transmission. Faecal DNA was extracted and amplified by nested PCR. The products were analysed by direct sequencing and the allele type was determined using an MLST website. Mother-to-child transmission was suspected in at least two of three families, and father-to-child transmission was suspected in one family.

Background: Antimicrobial therapy is necessary to eradicate Helicobacter pylori infection. The emergence of antimicrobial‐resistant bacteria poses a threat to continued treatment with antimicrobial agents. For those who prescribe antimicrobial therapy, it is necessary to constantly monitor the emergence of antimicrobial‐resistant bacteria.Method: H. pylori clinical isolates were collected in Japan from August 2018 to December 2020 for antimicrobial susceptibility testing. The agar dilution method was used for the determination of the minimum inhibitory concentration (MIC) of clarithromycin (CLR), amoxicillin (AMX), metronidazole (MNZ), and sitafloxacin (STX).Results: MICs for 938 H. pylori isolates were examined. The primary resistance rates of H. pylori clinical isolates for CLR, AMX, MNZ, and STX in Japan were 35.5%, 2.7%, 4.2%, and 27.6%, respectively. The primary resistance rates for CLR, AMX, and MNZ were significantly higher than those of the 2002–2005 isolates. The resistance rate for CLR was significantly higher in females (males: 30.7%, females: 41.5%, p < 0.001) and higher in the ≤29 years age group (54.8%) than in the other age groups, although there were no significant differences (p = 0.104). The MNZ resistance rate was significantly higher in the ≤29 years age group than in the other age groups (p = 0.004). The resistance rate for STX increased with age, but a significant difference was only seen between the 30–49 years age group and the ≥70 years age group (p < 0.001), and the resistance rate was significantly higher in strains isolated in the Kyushu region than in the other regions (p < 0.001).Conclusions: The primary resistance rates for CLR, AMX, and MNZ of H. pylori clinical isolates in Japan were higher than those of the 2002–2005 isolates. Continuous surveillance is needed to monitor the trends in antimicrobial‐resistant H. pylori.