Alcohol, Smoking, and Dietary Status and Susceptibility to Malignant Lymphoma in Japan: Results of a Hospital-based Case-control Study at Aichi Cancer Center

Recent increase in the incidence of malignant lymphoma (ML) suggests possible involvement of lifestyle or environmental factors in its genesis. However, evidence for an effect of lifestyle factors, especially diet, on ML risk among Japanese is lacking. To explore the possibility that lifestyle factors exert an influence, we have conducted a hospital-based case-control study with 333 histo-logically confirmed ML cases and 55 904 non-cancer controls who first visited Aichi Cancer Center Hospital between 1988 and 1997. Multiple logistic regression analysis showed regular alcohol consumption to be associated with reduced risk of ML, whereas no risk change was observed for smoking. Some other factors including intake of vegetables (carrots and pumpkin), pork and fish showed partial associations, but their significance needs further clarification. From the previous study on genetic background for ML [Matsuo et al., Blood , 97, 3205–3209 (2001)], genetic variation combined with limited environmental factors should be targeted in future studies.     

Evaluation of a Novel Artificial Pancreas: Closed Loop Glycemic Control System With Continuous Blood Glucose Monitoring

A closed‐loop glycemic control system using an artificial pancreas has been applied with many clinical benefits in Japan since 1987. To update this system incorporating user‐friendly features, we developed a novel artificial pancreas (STG‐55). The purpose of this study was to evaluate STG‐55 for device usability, performance of blood glucose measurement, glycemic control characteristics in vivo in animal experiments, and evaluate its clinical feasibility. There are several features for usability improvement based on the design concepts, such as compactness, display monitor, batteries, guidance function, and reduction of the preparation time. All animal study data were compared with a clinically available artificial pancreas system in Japan (control device: STG‐22). We examined correlations of both blood glucose levels between two groups (STG‐55 vs. control) using Clarke's error grid analysis, and also compared mean glucose infusion rate (GIR) during glucose clamp. The results showed strong correlation in blood glucose concentrations (Pearson's product‐moment correlation coefficient: 0.97; n = 1636). Clarke's error grid analysis showed that 98.4% of the data fell in Zones A and B, which represent clinically accurate or benign errors, respectively. The difference in mean GIRs was less than 0.2 mg/kg/min, which was considered not significant. Clinical feasibility study demonstrated sufficient glycemic control maintaining target glucose range between 80 and 110 (mg/dL), and between 140 and 160 without any hypoglycemia. In conclusion, STG‐55 was a clinically acceptable artificial pancreas with improved interface and usability. A closed‐loop glycemic control system with STG‐55 would be a useful tool for surgical and critical patients in intensive care units, as well as diabetic patients.     

Delayed onset adenosine deaminase deficiency associated with acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is a monophasic, immune-mediated demyelinating disorder that can appear after either immunizations or, more often, infections. Magnetic resonance imaging of patients shows inflammatory lesions in the brain and spinal cord. An immune-mediated mechanism may play a role in this disease, although its precise pathogenesis remains unclear. In this study, a 2-year-old boy presented with ADEM, and he showed improvement on treatment with high-dose intravenous corticosteroids. At the age of 3 years, the presence of recurrent bronchitis, bronchiectasia, and lymphopenia suggested that the patient was suffering from combined immunodeficiency. The patient was finally diagnosed with delayed onset adenosine deaminase deficiency. Delayed onset adenosine deaminase deficiency is frequently associated with autoimmune diseases, including thyroiditis and cytopenia, both of which were observed in the patient. The ADEM in this patient may be a presentation of delayed onset adenosine deaminase deficiency.     

Development of germinoma during the treatment of systemic-onset juvenile idiopathic arthritis with infliximab

We report a 19-year-old patient with systemic-onset juvenile idiopathic arthritis (JIA) who developed a mediastinal germinoma during treatment with infliximab. Although the cancer risk of infliximab is controversial, this agent may have accelerated the growth of the germinoma. We conclude that the indications for tumor necrosis factor (TNF) inhibitors should be strictly decided and that a nationwide cohort study is necessary to assess the risk of cancer in patients with JIA exposed to biologics.     

Aldehyde dehydrogenase 2 (ALDH2) genotype affects rectal cancer susceptibility due to alcohol consumption

BACKGROUND: Epidemiologic studies have shown the association between alcohol consumption and colorectal cancer, especially for rectal cancer. The alcohol related enzyme encoding gene ALDH2 has polymorphism Glu487Lys, and 487Lys allele is closely linked with phenotypic loss of enzyme activity. MATERIALS AND METHODS: A hospital-based case-control study was conducted with 72 colon and 70 rectal cancer cases and 241 non-cancer controls to evaluate the alcohol consumption and ALDH2 Glu487Lys polymorphism. The logistic regression model was applied to estimate the odds ratios (ORs). RESULT: The crude ORs for Glu/Lys and Lys/Lys genotype relative to Glu/Glu for colon and rectal cancer were not statistically significant. However, with the rectal cancer analysis, the ORs for high alcohol consumption were greater with 487Glu/Lys genotype compared with Glu/Glu, albeit not. CONCLUSIONS: These observations suggested rectal cancer risk might be influenced by ALDH2 gene polymorphism. The prevention effect by alcohol reduction might differ by ALDH2 genotype.     

细胞色素P450 2E1基因多态性与结直肠癌易感性的关系

目的：研究细胞色素P4502E1（CYP2E1）基因多态性与结直肠癌易感性的关系。方法：对315例结直肠癌患者和439名对照人群进行病例对照研究,PCR-RFLP检测其基因型。结果：1）c1/c1、c1/c2和c2/c2基因型分布频度在结直肠癌组和对照组间差异有统计学意义,Х^2=6.58,P=0.037。与c1/c1基因型相比,c2/c2基因型发生结肠癌的危险性显著升高;2）有饮酒习惯者发生结直肠癌的危险性显著升高;3）CYP2E1RsaⅠ多态与饮酒习惯有显著的协同作用。结论：CYP2E1RsaⅠ基因多态和饮酒习惯影响结直肠癌的易感性,二者在结直肠癌发生中有显著的协同作用。     

Clinical analysis of patients with hepatocellular carcinoma with non-A, non-B hepatitis virus

An analysis of 242 patients with a hepatocellular carcinoma (HCC) has shown that 65 patients without a hepatitis B virus (HBV), alcohol abuse, or a transfusion history and 17 posttransfusion patients had a mean death age of 65.5 +/- 10.2 and 62.1 +/- 8.4 years respectively. The average age of 65 patients was 8.5 years older than those with a HBV and without a alcohol abuse history. Of 17 patients, 3 with a HBV had a mean death age of 55.3 +/- 10.8 years and the interval time from transfusion to a HCC was significantly shorter than in other post-transfusion patients.     

Variation of HLA class II genes in the Nganasan and Ket, two aboriginal Siberian populations.

Allelic frequencies at the three most polymorphic loci of the HLA class II region (DRB1, DQA1 and DQB1) were determined in the Nganasan and Ket, the remnants of the two most ancient groups in the Lower Yenisey River/Taimyr Peninsula region in northern Siberia. By single-stranded conformational polymorphism typing, verified by sequencing, 19 HLA-DRB1-DQA1-DQB1 haplotypes and 15 HLA-DRB1, seven DQA1 and 11 DQB1 alleles were found. The most frequent alleles were DRB1*1301 (23.5%), DQA1*0103 (29.4%), *0501/03/05 (29.4%), and DQB1*0301/09 (32.4%) in the Ket, and DRB1*0901 (25%), DQA1*0301 (39.6%), and DQB1*0301/09 (37.5%) in the Nganasan. The distribution patterns and comprehensive phylogenic analysis based on the haplotype frequencies of 17 Siberian populations suggest that the founders of both the Ket and the Nganasan came from Palaeolithic populations in the Altai-Sayan Upland.