Diabetes mellitus and cancer risk: Pooled analysis of eight cohort studies in Japan

Although a growing body of evidence suggests a link between diabetes and cancer, it is not clear whether diabetes independently increases the risk of cancer. We conducted a comprehensive assessment of the association between pre‐existing diabetes and total and site‐specific cancer risk based on a pooled analysis of eight cohort studies in Japan (>330 000 subjects). We estimated a summary hazard ratio by pooling study‐specific hazard ratios for total and site‐specific cancer by using a random‐effects model. A statistically increased risk was observed for cancers at specific sites, such as colon (hazard ratio; HR = 1.40), liver (HR = 1.97), pancreas (HR = 1.85) and bile duct (HR = 1.66; men only). Increased risk was also suggested for other sites, and diabetes mellitus was associated with an overall 20% increased risk in total cancer incidence in the Japanese population. The association between these two diseases has important implications for reiterating the importance of controlling lifestyle factors and may suggest a possible strategy for cancer screening among patients with diabetes. Studies continuously investigating the risk factors for diabetes are also important.     

Persistent déjà vu associated with hyperperfusion in the entorhinal cortex

Déjà vu is a common experience among the normal population. However, in individuals with temporal lobe epilepsy, it often occurs as a seizure manifestation. The specific cause of such déjà vu is not yet known. Here, we report a case of epilepsy with persistent déjà vu. The patient described the state as if he were living the same life he had lived before. Blood perfusion single-photon-emission computed tomography (SPECT) performed during the persistent déjà vu showed hyperperfusion in the left medial temporal area; discontinuation of déjà vu was accompanied by disappearance of the hyperperfused area on SPECT. Analysis with three-dimensional co-registration of SPECT and MRI revealed that the hyperperfused area during the persistent déjà vu was in the entorhinal cortex of the left temporal lobe. According to recent theories of recognition memory, malfunction of the parahippocampal area may cause déjà vu. It is also suggested that epileptic activity in the parahippocampal area, especially the entorhinal cortex, may elicit déjà vu.     

Insulin-like growth factor 2 hypomethylation of blood leukocyte DNA is associated with gastric cancer risk

To determine whether or not the methylation status of blood leukocyte DNA can be used as a surrogate marker of the risk for cancer, we quantitatively determined the methylation levels of insulin-like growth factor 2 (IGF2) and TUSC3 in 299 gastric cancer cases, and 299 age- and gender-matched controls. The IGF2 methylation levels in blood leukocyte DNA of the cases were lower than those of the healthy controls and there was a significant trend of increasing gastric cancer risk with decreasing methylation level of IGF2. Patients with hypermethylated IGF2 in blood leukocyte DNA showed a significantly better survival rate than those with hypomethylated IGF2, indicating that the IGF2 methylation level in blood leukocyte DNA can be a possible marker not only of the risk for but also of the prognosis of gastric cancer. In contrast, the TUSC3 methylation level in blood leukocyte DNA was higher in the cases than in the healthy controls, but the difference was not significant. The past lifestyle and clinicopathological characteristics of the participants were analyzed for any relationship with the methylation level. With aging and smoking, methylation of IGF2 and TUSC3 decreased and increased in blood leukocyte DNA, respectively. These results indicate that the methylation level of IGF2 in blood leukocyte DNA may be used as an important surrogate marker of the risk for gastric cancer.     

Declining trends in prevalence of Helicobacter pylori infection by birth‐year in a Japanese population

Gastric cancer incidence and mortality have been decreasing in Japan. These decreases are likely due to a decrease in prevalence of Helicobacter pylori infection. Our aim was to characterize the trends in prevalence of H. pylori infection focused on birth‐year. We carried out a cross‐sectional study that included 4285 subjects who were born from 1926 to 1989. We defined H. pylori infection by the serum H. pylori antibody titer. Individuals having H. pylori infection and those with negative H. pylori antibody titer and positive pepsinogen test were defined as high‐risk individuals for gastric cancer. We estimated the birth‐year percent change (BPC) of the prevalence by Joinpoint regression analysis. The prevalence of H. pylori infection among the subjects born from 1927 to 1949 decreased from 54.0% to 42.0% with a BPC of −1.2%. It was followed by a rapid decline in those born between 1949 (42.0%) and 1961 (24.0%) with a BPC of −4.5%, which was followed by those born between 1961 (24.0%) and 1988 (14.0%) with a BPC of −2.1%. The proportion of high‐risk individuals for gastric cancer among the subjects born from 1927 to 1942 decreased from 62.0% to 55.0% with a BPC of −0.8%. A subsequent rapid declining trend was observed in those born between 1942 (55.0%) and 1972 (18.0%) with a BPC of −3.6%, and then it became stable. These remarkable declining trends in the prevalence of H. pylori infection by birth‐year would be useful to predict the future trend in gastric cancer incidence in Japan.     

PAR-2 deficient CD4+ T cells exhibit downregulation of IL-4 and upregulation of IFN-gamma after antigen challenge in mice.

BACKGROUND: To investigate the functional role of protease activated receptor (PAR) -2 in T lymphocytes, we analyzed TCR-mediated inflammatory cytokine production using PAR-2 deficient (KO) and wild type (WT) mice. METHODS: Production of serum IgE and cytokines by spleen CD4+ T cells was determined in OVA-sensitized and OVA-challenged mice of PAR-2 KO in contrast to WT mice. Phosphorylation of JNK1 and 2 was determined by Western blotting. RESULTS: A reduction in serum levels of IgE and IL-4 production by splenic CD4+ T cells from OVA-sensitized and OVA-challenged KO mice compared to WT mice was observed. By contrast, IFN-gamma production was upregulated after antigen stimulation in KO mice. Anti-CD3-mediated phosphorylation of JNK1 was upregulated in splenic CD4+ T cells from KO mice compared to WT mice. CONCLUSIONS: PAR-2 participates in the regulation of T cell cytokine production that may be caused by modulation of JNK1 phosphorylation.     

The real impact of telaprevir dosage on the antiviral and side effects of telaprevir,pegylated interferon and ribavirin therapy for chronic hepatitis C patients with HCV genotype 1

Triple therapy with telaprevir, pegylated interferon and ribavirin has been reported to improve antiviral efficacy but have potentially severe adverse effects in patients with chronic hepatitis C. To avoid the severe effects of telaprevir, lowering the dose has been suggested. However, impact of dosage changes on antiviral and adverse effects remains unclear. One hundred and sixty‐six Japanese patients with HCV genotype 1 were treated with triple therapy. The drug exposure of each medication was calculated by averaging the dose actually taken. The overall SVR rate was 82%. The telaprevir discontinuation rate was 26%. The factors associated with discontinuation were an older age (≥65 y.o.) and a higher average dose during treatment. The telaprevir discontinuation rates were 42%, 25% and 14% in patients at ≥35, 25–35 and <25 mg/kg/day of telaprevir and 58% in older patients at ≥35 mg/kg/day of TVR. The factors associated with SVR were treatment‐naïve, relapse to previous treatment, higher average telaprevir dose during treatment and completion of treatment. The SVR rate was higher, at 91%, in patients at 25–35 mg/kg/day of telaprevir than the 71% and 78% observed in those at <25 and ≥35 mg/kg/day of drug. In Japanese patients, a mean telaprevir dose of 25–35 mg/kg/day during treatment can augment its efficacy in triple therapy for patients with HCV genotype 1.