CYP1A1, GSTM1 and GSTT1 genetic polymorphisms and gastric cancer risk among Japanese: A nested case–control study within a large‐scale population‐based prospective study

Cytochrome P450 (CYP) 1A1 and glutathione S‐transferases (GST) M1 and T1 are major enzymes in the carcinogen metabolizing pathway. We examined the association between single nucleotide polymorphisms (SNPs) of CYP1A1 (rs4646421, rs4646422 and rs1048943), GSTM1 and GSTT1 and gastric cancer risk in Japan. This is a nested case–control study (457 cases and 457 matched controls) of our population‐based cohort involving 36,745 subjects who answered a baseline questionnaire and supplied blood samples. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using conditional logistic regression models. We found that CYP1A1 (rs4646422) variant allele was associated with a statistically significant increased risk of gastric cancer compared with the homozygous wild‐type genotype (OR = 1.65; 95% CI = 1.17–2.32). GSTM1 null, GSTT1 null and GSTM1/T1 both or either null genotypes were associated with increased risk, but not statistically significantly. Combination of the CYP1A1 (rs4646422) variant allele and GSTM1/T1 both or either null genotypes was associated with a statistically significant increased risk compared with the combination of the CYP1A1 homozygous wild‐type genotype and the GSTM1/T1 both active genotypes. In addition, compared with CYP1A1 (rs4646422) homozygous wild‐type genotypes in those who were never‐smokers, CYP1A1 variant alleles in those who smoked ≥30 pack‐years were associated with an increased risk; neither gene–gene nor gene–environment interactions were significant. The CYP1A1 (rs4646422) polymorphism might be involved in gastric carcinogenesis among the Japanese population.     

Smoking is a risk factor for development of adult T-cell leukemia/lymphoma in Japanese human T-cell leukemia virus type-1 carriers

Background and purpose

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive hematological malignancy caused by human T-cell leukemia virus type-1 (HTLV-1); no effective methods have yet been identified to prevent development of ATLL in carriers of HTLV-1. This study investigated the association between cigarette smoking and the risk of ATLL development among Japanese carriers of HTLV-1.

Methods

This study examined the association between smoking and development of ATLL in a cohort of 1,332 Japanese HTLV-1 carriers aged 40–69 years free of ATLL at baseline from two different HTLV-1-endemic areas of Japan. Cox proportional hazards models adjusted for sex, geographic area, age at baseline, and alcohol drinking were used to estimate the effect of cigarette smoking on ATLL development.

Results

Between 1993 and 2012, 25 new ATLL cases were identified among these subjects. The overall crude incidence rate for ATLL was 1.08 per 1,000 person-years among HTLV-1 carriers and was higher among male carriers than among female carriers (2.21 vs. 0.74). The risk of ATLL development increased significantly with increasing numbers of cigarettes smoked per day (hazard ratio for every increment of 20 cigarettes, 2.03; 95 % confidence interval (CI) 1.13–3.66 overall, 2.07 (95 % CI 1.13–3.73) in male carriers).

Conclusions

Cigarette smoking may influence ATLL development among HTLV-1 carriers in Japan.

     

Prevalence of chronic kidney disease and administration of RA-related drugs in patients with RA: The NinJa 2012 study in Japan

Objectives: To estimate the prevalence of chronic kidney disease in patients with rheumatoid arthritis (RA) and the administration of disease-modifying anti-rheumatic-drugs (DMARDs), using data from the National Database of Rheumatic Disease by iR-net in Japan (NinJa) 2012 study.

Methods: From a total of 11,940 RA patients, 7135 who underwent an estimated glomerular filtration rate (eGFR) test were studied. Renal dysfunction staging was assessed using Japanese eGFR equations and classified according to the Kidney Disease Improving Global Outcomes 2012 clinical practice guideline.

Results: The prevalence of GFR stages was as follows: stage G1, 25.4%; stage G2, 55.9%; stage G3, 17.5%; stage G4, 0.8%; and stage G5, 0.2%. Overall, 92.7% of patients received at least one DMARD. Sulfasalazine, tacrolimus, and biologics (except inflixmab) were administered in all GFR stages. Methotrexate was not prescribed in patients with stage G5, but methotrexate 3.5?mg/week (mean) was prescribed in four patients (6.8%) with stage G4. Non-steroidal anti-inflammatory drugs and glucocorticoids were prescribed in 40.5% and 43.7% of patients, respectively.

Conclusion: The prevalence of kidney disease in this large sample of RA patients was higher than that in the general population, and the results suggest that RA patients with renal dysfunction require careful drug selection.     

CASE REPORT: A long-term survivor of jejunal leiomyosarcoma with liver metastasis: Effective transcathetel arterial embolization for hepatic metastatic foci

We report a case of jejunal leiomyosarcoma with liver metastases in a 52-year-old Japanese male. An echogram demonstrated multiple cystic liver masses in April 1991. The diagnosis of metastatic leiomyosarcoma was made on the basis of characteristic hepatic angiography images and liver biopsy findings. The jejunal leiomyosarcoma was resected and unresectable liver metastatic foci were treated repeatedly with transcathetel arterial embolization. Transcathetel arterial embolization was considered to be effective in this case as the patient survived 4 years and 9 months after the first treatment.     

Sclerotherapy for gastric fundal variceal bleeding: Is complete obliteration possible without cyanoacrylate?

BACKGROUND: Many studies have suggested that endoscopic obliteration using cyanoacrylate for bleeding gastric fundal varices is effective. However, serious complications by injection of cyanoacrylate into varices have also been reported. METHODS: Thirty patients with bleeding gastric fundal varices underwent endoscopic injection sclerotherapy using 5% ethanolamine oleate under fluoroscopic guidance plus infusion of vasopressin and a transdermal nitroglycerin patch. The injection of 5% ethanolamine oleate was continued until it filled the varices and their feeder veins under fluoroscopic guidance. The injection needle was removed while thrombin glue was sprayed at the puncture site through the side hole of the injector needle to prevent bleeding from the puncture site. RESULTS: Complete hemostasis was achieved in 28/30 patients (93.3%). The cumulative rebleeding rate after 1, 3 and 5 years was 13%, 19% and 19%, respectively. The 1-, 3-, and 5-year cumulative mortality rates were 31%, 54% and 59%, respectively. There was no complication related to infusion of vasopressin and sclerotherapy procedure. CONCLUSION: The sclerotherapy method carried out using 5% ethanolamine oleate combined with infusion of vasopressin under fluoroscopic guidance might be a feasible method for obliteration of gastric fundal varices as an alternative to cyanoacrylate.     

Desquamative interstitial pneumonia may progress to lung fibrosis as characterized radiologically

Background and objective: In some patients, desquamative interstitial pneumonia may progress to lung fibrosis. The aim of this study was to assess the long‐term radiological follow‐up results in patients with desquamative interstitial pneumonia. Methods: Among 75 patients suspected of having desquamative interstitial pneumonia, 31 who fulfilled the criteria were included in this study. Clinical characteristics at presentation, responses to treatment and long‐term follow‐up were evaluated. Results: The 31 patients were predominantly males (94%), and the mean age was 55 years; 93% (28/30) had a history of smoking. The clinical findings included high serum levels of lactate dehydrogenase and immunoglobulin G. Bronchoalveolar lavage (26 patients, 84% of cases) frequently showed an increased percentage of eosinophils (mean 17%). Computed tomography (CT) or high resolution (HR) CT at presentation showed ground glass opacities and/or consolidation in all patients, with one third of patients also showing thin‐walled cysts within the ground glass opacities. There was no honeycombing on CT or HRCT scans at presentation. Corticosteroid therapy was effective early in the course of the disease; long‐term follow‐up (mean 99 months) of 31 patients showed only one death due to progression of the disease, but long‐term follow‐up of 14 patients (mean 125 months) by HRCT showed the development of new thin‐walled cysts and honeycombing in five and lung cancer in four patients, respectively. Conclusions: In a proportion of patients, desquamative interstitial pneumonia may progress to lung fibrosis with honeycombing on HRCT, despite therapy.     

Effectiveness of the combined approach for assessing social gradients in stroke risk among married women in Japan

Background

Analysis of the effects of social gradients on women’s health requires a suitable means of assessing social standing.

Methods

We compared social gradients in stroke risk among 9317 married Japanese women from the Japan Public Health Center-based Prospective Study over a 16-year period. Social gradient was estimated by 3 methods of indicating social position: education level derived by using the individual approach (woman’s own educational level), the conventional approach (using her partner’s educational level), and the combined approach (combining the woman’s and her partner’s educational levels).

Results

As compared with the lowest educational group, stroke risk was similar among women in the highest educational group using the individual approach and lower, but not significantly so, with the conventional approach. With the combined approach, however, the age- and area-adjusted hazard ratio (HR) was significantly lower among the highest education group as compared with the lowest group (HR = 0.52, 95% CI: 0.36, 0.76), and the relative index of inequality was significant (RII = 0.48, 95% CI: 0.32, 0.72). Using the combined approach, the results were similar irrespective of employment status. In the combined highest educational group, stroke risk among unemployed women was significantly reduced by 54%, while stroke risk for employed women was significantly reduced by 46%, as compared with the lowest educational group, with RIIs of 0.42 (95% CI: 0.21, 0.85) and 0.49 (0.30, 0.80), respectively.

Conclusions

The results suggest that a combined approach better reflects social standing among married women in Japan.Key words: social gradient, measure, stroke, women, Japan     

Oral infection control to assist infliximab therapy in a Behçet's disease patient with severe eye inflammation in response to dental treatment: a case report

We report a case of Behçet's disease which was aggravated by psychological stress and oral infection. The control of oral infection under medical and dental collaboration is important for providing Behçet's disease patients with the optimal medical care and for facilitating the relief of the primary disease.     

Epidermal adenylate cyclase system is regulated by diacylglycerol-protein kinase C signal, but not by calcium signal

The breakdown of inositol phospholipids is an important transmembrane signalling system that is composed of two kinds of signals: the diacylglycerol-protein kinase C signal, and the inositol trisphosphate-Ca2+ signal. Using membrane-permeable diacylglycerol, I-oleoyl-2-acetylglycerol (OAG), and calcium ionophore, A-23187, the effects of these chemicals on the epidermal adenylate cyclase system were investigated. OAG increased forskolin- and cholera toxin-induced cyclic AMP accumulations, but receptor adenylate cyclase responses were markedly decreased by treatment with OAG. The effects of OAG were inhibited by the protein kinase C inhibitor, H-7. Calcium ionophore, A-23187, had no effect on the epidermal adenylate cyclase responses. Combinations of OAG and A-23187 (as well as the calcium chelator, EGTA), showed that the action of OAG was mostly unaffected by the modulation of intracellular and extracellular Ca2+ concentrations. The results suggest that among the signals triggered by the breakdown of inositol phospholipids, only diacylglycerol-protein kinase C signal is involved in the regulation of the epidermal adenylate cyclase system.