社会経済的地位と消化器がんの関係について : 症例対照研究

Although socioeconomic status (SES) has been associated with cancer risk, little research on this association has been done in Japan. To evaluate the association between SES and digestive tract cancer risk, we conducted a case-control study for head and neck, esophageal, stomach, and colorectal cancers in 3188 cases and the same number of age- and sex-matched controls within the framework of the Hospital-based Epidemiological Research Program at Aichi Cancer Center III (HERPACC III). We employed the education level and areal deprivation index (ADI) as SES indicators. The association was evaluated with odds ratios (ORs) and 95% confidence intervals (CIs) by conditional logistic models adjusted for potential confounders. Even after allowance for known cancer risk factors, the education level showed linear inverse associations with head and neck, stomach, and colorectal cancers. Compared to those educated to junior high school, those with higher education showed statistically significantly lower risks of cancer (0.43 (95% CI: 0.27–0.68) for head and neck, 0.52(0.38–0.69) for stomach, and 0.52(0.38–0.71) for colorectum). Consistent with these results for the educational level, the ADI in quintiles showed positive associations with head and neck, esophageal, and stomach cancers (p-trend: p = 0.035 for head and neck, p = 0.02 for esophagus, and p = 0.013 for stomach). Interestingly, the positive association between ADI and stomach cancer risk disappeared in the additional adjustment for Helicobacter pylori infection and/or atrophic gastritis status. In conclusion, a lower SES was associated with an increased risk of digestive cancers in Japan and should be considered in cancer prevention policies for the target population.An association between socioeconomic status (SES) and cancer risk has been reported, but little is known in Asia. We revealed an association between SES, including education level and areal deprivation index (ADI), and digestive tract cancers in Japan. Lower SES was associated with an increased risk of digestive cancers. For stomach cancer, the positive association with ADI disappeared following an additional adjustment of Helicobacter pylori infection and/or atrophic gastritis status. Cancer prevention policy should consider both individual and regional perspectives by the integration of SES in the target population

A49T, V89L and TA repeat polymorphisms of steroid 5α-reductase type II and breast cancer risk in Japanese women

BACKGROUND: Breast cancer is hormone related, as are cancers of the endometrium, ovary, and prostate. Several studies have suggested that higher extracellular levels of androgens are associated with breast cancer risk, while biological evidence indicates that androgens are protective. The codon 49 alanine to threonine substitution (A49T), codon 89 valine to leucine substitution (V89L) and TA repeat polymorphisms of the steroid 5α-reductase type II (SRD5A2) gene are considered functional with respect to enzyme activity converting testosterone into dihydrotestosterone. To test the hypothesis that these three polymorphisms are associated with risk of breast cancer, a case–control study was conducted with patients of Aichi Cancer Center Hospital. METHODS: The cases were 237 patients histologically diagnosed with breast cancer, and the controls were 185 noncancer outpatients. DNA from peripheral blood was genotyped by PCR methods. RESULTS: The threonine allele of A49T was not found in our subjects. Compared with the V/V genotype of V89L, the L/L genotype was associated with a decreased risk (crude odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.36–1.05). This was also the case for the TA(9/9) genotype, with an OR of 0.58 (95% CI = 0.13–2.63) relative to TA(0/0). Among women with the TA(0/0) genotype, however, the OR for the L/L genotype was 0.46 (95% CI = 0.24–0.88) compared with the V/V genotype, and those with the V/V and TA(0/0) genotypes had the highest risk. The haplotype with the L and TA(9) repeat alleles was not found. CONCLUSION: This study is the first to our knowledge focusing on Japanese women, suggesting that SRD5A2 polymorphisms might have an association with breast cancer risk. Further large-sample studies will be required to confirm the association and to assess any interactions with environmental factors

Cross-conjugated isothianaphthene quinoids: a versatile strategy for controlling electronic structures

The elucidation of new structure–property relationships in π-conjugated molecules bearing quinoidal moieties is of relevance because of their use in organic electronics applications and their traditional assimilation as models of doped conducting polymers. Quinoidal oligothiophenes are ground state electronic hybrids between closed-shell Kekulé quinoidal and open-shell aromatic diradicaloid forms. The prominent contribution of the diradical character in longer oligomers beyond thiophene 4-mers results in a low stability, thereby limiting the ability to tune their properties. Thus, the control of these quinoidal/aromatic contributions is an important prerequisite to develop long quinoidal oligothiophenes. To address this problem, a series of quinoidal pentathiophenes with benzene-annelated isothianaphthene units were designed and successfully synthesized as stable structures. Combined molecular spectroscopies and theoretical modelling indicated that cross-conjugation appears upon the introduction of multiple benzene-annelated units, and that the number and position of the benzene-annelated units have a significant influence on the quinoidal/aromatic/cross-conjugated electronic structures. The newly developed quinoidal pentathiophenes functioned as organic semiconducting materials in transistor and near infrared phototransistor devices. This study demonstrates that modification of the cross-conjugated quinoidal structure is a promising strategy for fine-tuning electronic structures in π-extended quinoidal systems, which could help us to understand unique π-electronic features and to develop novel organic electronic materials.This work was supported by JSPS KAKENHI (20H02814, 20K21224, 20H05841, 20KK0123, 19K15505, 20H04639, 20K15352, 21K05213, 20H00379, 20H05833, and 20K15261), CREST (J205101030), NEDO (21500248-0), and “Dynamic Alliance for Open Innovation Bridging Human, Environmental and Materials” from The Ministry of Education, Culture, Sports, Science and Technology, Japan. We are grateful to Prof. Toshihiro Ohnishi for helpful discussion. The authors thank the Spanish Ministry of Science, Innovation and Universities MCIU and MINECO/FEDER of the Spanish Government (project PGC2018-098533-B-100), the Ministry of Science and Technology of the Spanish Government (project RED2018-102626-T) and the Junta de Andalucía, Spain (UMA18FEDERJA057). We also thank the Research Central Services (SCAI) of the University of Málaga. // Funding for open access charge: Universidad de Málag

HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide after Busulfan-Containing Reduced-Intensity Conditioning

AbstractAllogeneic hematopoietic stem cell transplantation (allo-SCT) using post-transplant cyclophosphamide (PTCy) is increasingly performed. We conducted a multicenter phase II study to evaluate the safety and efficacy of PTCy-based HLA-haploidentical peripheral blood stem cell transplantation (PTCy-haploPBSCT) after busulfan-containing reduced-intensity conditioning. Thirty-one patients were enrolled; 61% patients were not in remission and 42% patients had a history of prior allo-SCT. Neutrophil engraftment was achieved in 87% patients with a median of 19 days. The cumulative incidence of grades II to IV and III to IV acute graft-versus-host disease (GVHD) and chronic GVHD at 1 year were 23%, 3%, and 15%, respectively. No patients developed severe chronic GVHD. Day 100 nonrelapse mortality (NRM) rate was 19.4%. Overall survival, relapse, and disease-free survival rates were 45%, 45%, and 34%, respectively, at 1 year. Subgroup analysis showed that patients who had a history of prior allo-SCT had lower engraftment, higher NRM, and lower overall survival than those not receiving a prior allo-SCT. Our results suggest that PTCy-haploPBSCT after busulfan-containing reduced-intensity conditioning achieved low incidences of acute and chronic GVHD and NRM and stable donor engraftment and low NRM, particularly in patients without a history of prior allo-SCT

GWAS for Japanese CSC

PURPOSE. Central serous chorioretinopathy (CSC) is a retinal disorder that often affects the vision of middle-aged people yet the molecular mechanisms of CSC remain unknown. This study was conducted to identify genetic factors influencing individual differences in susceptibility to CSC. METHODS. A two-stage genome-wide association study (GWAS) was conducted with a total of 320 unrelated Japanese idiopathic CSC cases and 3245 population-based controls. In a discovery stage, 137 unrelated Japanese idiopathic CSC cases and 1174 population-based controls were subjected to GWAS, followed by a replication study using an additional 183 individuals with idiopathic CSC and 2071 population-based volunteers. The results of the discovery and replication stages were combined to conduct a meta-analysis. RESULTS. In the two-stage GWAS, rs11865049 located at SLC7A5 in chromosome 16q24.2 was identified as a novel disease susceptibility locus for CSC, as evident from the discovery and replication results using meta-analysis (combined P = 9.71 × 10−9, odds ratio = 2.10). CONCLUSIONS. The results of the present study demonstrated that SLC7A5 might be the potential candidate gene associated with CSC, indicating a previously unidentified molecular mechanism of CSC

Non-BAC Component but not Epidermal Growth Factor Receptor Gene Mutation is Associated with Poor Outcomes in Small Adenocarcinoma of the Lung

ObjectiveThe purpose of this study was to identify risk factors for poor clinical outcome after surgical resection of small lung adenocarcinoma.Materials and MethodsClinical records of 127 patients who had pathologic stage IA lung adenocarcinoma 20 mm or less and who had undergone a lobectomy with mediastinal lymph node dissection were reviewed. The percentage of non-bronchioloalveolar carcinoma (non-BAC) components quantified objectively, and epidermal growth factor receptor gene (EGFR) mutation determined by polymerase chain reaction-based assay were retrospectively linked with clinical data.ResultsBased on the percentage of non-BAC component, 127 patients were classified as follows: 26 in group I, BAC, 46 in group II mixed subtype with ≥ 50% BAC, 18 in group III, mixed subtype with under 50% BAC, and 37 in group IV, mixed subtype with all non-BAC components or a pure pattern of one of the non-BAC components. Groups I and II were considered to be a “low non-BAC component type” and groups III and IV were considered to be a “high non-BAC component type.” EGFR mutations in exon19 and exon21 were observed in 64 patients (50.4%). In terms of recurrence, the high non-BAC component type was the only independent factor for recurrence (p = 0.029). Regarding survival, the high age (p = 0.028) and high non-BAC component type (p = 0.046) were independent risk factors for poor overall survival. They were also independent risk factors for poor disease-free survival (p = 0.025 and p = 0.027, respectively).ConclusionThe high non-BAC component but not EGFR mutation status, is an independent risk factor for both recurrence and poor prognosis in patients with stage IA lung adenocarcinoma ≤20 mm