Cancer and disease profiles for PTEN pathogenic variants in Japanese population.

A germline alteration in the PTEN gene causes a spectrum of disorders conceptualized as PTEN hamartoma tumor syndrome (PHTS), which show high risk of tumor development and a highly variable and complex phenotype. The diagnosis of PHTS is established in a proband by identification of a heterozygous germline PTEN pathogenic variant on molecular genetic testing. In this study, to understand more PTEN-associated clinical phenotype and PHTS in a Japanese population, we extracted 128 germline PTEN rare variants from 113,535 adult Japanese registered in Biobank Japan (BBJ), and categorized 29 pathogenic/likely pathogenic variants in 30 individuals (0.

Germline Susceptibility to Renal Cell Carcinoma and Implications for Genetic Screening.

Purpose: Genetic susceptibility to nonsyndromic renal cell carcinoma (RCC) remains poorly understood, especially for different histological subtypes, as does variations in genetic predisposition in different populations. The objectives of this study were to identify risk genes for RCC in the Canadian population, investigate their clinical significance, and evaluate variations in germline pathogenic variants (PVs) among patients with RCC across the globe.

Materials And Methods: We conducted targeted sequencing of 19 RCC-related and 27 cancer predisposition genes for 960 patients with RCC from Canada and identified genes enriched in rare germline PVs in RCC compared with cancer-free controls.

Development of an umbilical cord blood transplantation-specific nonrelapse mortality risk assessment score.

Higher rate of nonrelapse mortality (NRM) remains yet to be resolved in umbilical cord blood transplantation (UCBT). Considering that UCBT has some unique features compared with allogeneic hematopoietic cell transplantation from other graft sources, a UCBT-specific NRM risk assessment system is required. Thus, in this study, we sought to develop a UCBT-specific NRM Risk Assessment (CoBRA) score.

Trends in non-Hodgkin lymphoma mortality rate in Japan and the United States: A population-based study.

Characterizing trends in mortality rates with consideration of trends in incidence rates at the population level could help identify unmet needs in public health and provide essential indicators of cancer control. In the late 20th century, the arrival of the first molecular targeted agent, rituximab, for non-Hodgkin lymphoma (NHL) led to a paradigm shift in NHL treatment. However, the public health impact of this arrival has not been fully clarified.

Personalized medicine with germline pathogenic variants: Importance of population- and region-wide evidence.

Rare germline pathogenic variants in cancer-predisposing genes have a high impact and potential for clinical utility. In the last 30 years, based on evidence of cancer risk associated with germline pathogenic variants, several measures have been suggested for personalized medicine, including the development of novel treatments, treatment stratification, risk reduction by surgical measures, chemoprevention, removal of environmental factors, and surveillance for early detection among specific high-risk individuals. However, this evidence is mainly based on evaluations of European populations.

, Homologous-Recombination Genes, and Gastric Cancer.

Background: infection is a well-known risk factor for gastric cancer. However, the contribution of germline pathogenic variants in cancer-predisposing genes and their effect, when combined with infection, on the risk of gastric cancer has not been widely evaluated.

Methods: We evaluated the association between germline pathogenic variants in 27 cancer-predisposing genes and the risk of gastric cancer in a sample of 10,426 patients with gastric cancer and 38,153 controls from BioBank Japan.

Fludarabine plus reduced-intensity busulfan versus fludarabine plus myeloablative busulfan in patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (HCT) offers a possible cure for patients with relapsed and refractory non-Hodgkin lymphoma (NHL) through potentially beneficial graft versus lymphoma effects. However, allogeneic HCT is associated with high nonrelapse mortality (NRM). Fludarabine with reduced-intensity busulfan (Flu/Bu2) and myeloablative busulfan (Flu/Bu4) are commonly used in conditioning regimens for allogeneic HCT; however, data on their use in patients with NHL is limited.

Association between early corticosteroid administration and long-term survival in non-infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation.

Non-infectious pulmonary complications (NIPCs) after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with poor outcomes. It is important to maximize the effectiveness of primary treatment because secondary treatment has not been established. We analyzed data from 393 patients who underwent allogeneic HSCT during a 10-year period.

Association between germline pathogenic variants in cancer-predisposing genes and lymphoma risk.

The application of advanced molecular technology has significantly expanded lymphoma classification, allowing risk stratification and treatment optimization. Limited evidence suggests the presence of a genetic predisposition in lymphoma, indicating the potential for better individualized clinical management based on a novel lymphoma classification. Herein, we examined the impact of germline pathogenic variants in 27 cancer-predisposing genes with lymphoma risk and explored the clinical characteristics of pathogenic variant carriers.

Expansion of Cancer Risk Profile for BRCA1 and BRCA2 Pathogenic Variants.

Importance: The clinical importance of genetic testing of BRCA1 and BRCA2 in breast, ovarian, prostate, and pancreatic cancers is widely recognized. However, there is insufficient evidence to include other cancer types that are potentially associated with BRCA1 and BRCA2 in clinical management guidelines.

Objective: To evaluate the association of BRCA1 and BRCA2 pathogenic variants with additional cancer types and their clinical characteristics in 100 914 individuals across 14 cancer types.

Autologous or allogeneic hematopoietic cell transplantation for relapsed or refractory PTCL-NOS or AITL.

Fit patients with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) in relapsed or refractory (R/R) disease status often receive salvage chemotherapy followed by autologous hematopoietic stem cell transplantation (autoHCT) or allogeneic HCT (alloHCT). However, there is no consensus on the type of HCT that should be applied for such patients. Herein, we retrospectively evaluated the survival outcome of 760 adult R/R PTCL-NOS or AITL patients who underwent the first HCT.

Association between germline pathogenic variants and breast cancer risk in Japanese women: The HERPACC study.

Approximately 5%-10% of breast cancers are hereditary, caused by germline pathogenic variants (GPVs) in breast cancer predisposition genes. To date, most studies of the prevalence of GPVs and risk of breast cancer for each gene based on cases and noncancer controls have been conducted in Europe and the United States, and little information from Japanese populations is available. Furthermore, no studies considered confounding by established environmental factors and single-nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) together in GPV evaluation.

Possible prognostic impact of WT1 mRNA expression at day + 30 after haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide for patients with myeloid neoplasm: a multicenter study from the Okayama Hematological Study Group.

Background: Previous studies have revealed that relapse of myeloid neoplasms after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be predicted by monitoring Wilms' tumor 1 (WT1) mRNA expression. However, only a few studies have investigated patients who received human leukocyte antigen-haploidentical stem cell transplantation with posttransplant cyclophosphamide (PTCY-haplo). In this study, we investigated the relationship between WT1 mRNA levels and clinical outcomes in the PTCY-haplo group, and compared them with those in the conventional graft-versus-host disease prophylaxis group (conventional group).

Low-intensity cigarette smoking and mortality risks: a pooled analysis of prospective cohort studies in Japan.

Background: Increasing proportions of smokers in Japan smoke <10 cigarettes per day (CPD). Yet, the health risks of low-intensity smoking in Asia are poorly understood.

Methods: We performed a pooled analysis of 410 294 adults from nine population-based prospective cohort studies participating in the Japan Cohort Consortium.

Impact of the combination of donor age and HLA disparity on the outcomes of unrelated bone marrow transplantation.

Impact of donor age considering HLA disparity on hematopoietic cell transplantation (HCT) outcomes has not been fully evaluated. We evaluated 8486 patients who received unrelated bone marrow transplantation (UR-BMT) from 8/8 or 7/8 HLA-matched donors. Compared to 8/8 HLA-matched younger donors (<40 years), 8/8 HLA-matched older donors (subdistribution hazard ratio [SHR], 1.

Metabolites Produced by sp. 32K Promote Biofilm Formation in Coculture with sp. ME121.

Previously, we reported that the coculture of motile sp. ME121 and non-motile sp. 32K, isolated from the same soil sample, displayed accelerated motility of strain ME121 due to an extracellular polysaccharide (EPS) produced by strain 32K.

Changing trend in mortality rate of multiple myeloma after introduction of novel agents: A population-based study.

Previously, the main treatment for multiple myeloma (MM) was cytotoxic chemotherapies, including autologous stem-cell transplantation (ASCT), but survival benefit in the elderly was limited. More recently, clinical trials and practical experience with novel agents with superior efficacy have shown improved survival, including in the elderly. However, this improvement cannot be simply interpreted as a decline in mortality rate that is an important public health measure of progress against cancer.

A Factor Produced by sp. 32K Accelerated the Motility of sp. ME121.

Motile sp. ME121 and non-motile sp. 32K were isolated from the same soil sample.

Across-Site Differences in the Mechanism of Alcohol-Induced Digestive Tract Carcinogenesis: An Evaluation by Mediation Analysis.

A genetic variant on ( rs671, Glu504Lys) contributes to carcinogenesis after alcohol consumption. Somewhat conversely, the Lys allele also confers a protective effect against alcohol-induced carcinogenesis by decreasing alcohol consumption due to acetaldehyde-related adverse effects. Here, we applied a mediation analysis to five case-control studies for head and neck, esophageal, stomach, small intestine, and colorectal cancers, with 4,099 cases and 6,065 controls, and explored the potentially heterogeneous impact of alcohol drinking on digestive tract carcinogenesis by decomposing the total effect of the Lys allele on digestive tract cancer risk into the two opposing effects of the carcinogenic effect (direct effect) and the protective effect (indirect effect mediated by drinking behavior).

Impact of PSCA Polymorphisms on the Risk of Duodenal Ulcer.

Background: While duodenal ulcer (DU) and gastric cancer (GC) are both H. pylori infection-related diseases, individuals with DU are known to have lower risk for GC. Many epidemiological studies have identified the PSCA rs2294008 T-allele as a risk factor of GC, while others have found an association between the rs2294008 C-allele and risk of DU and gastric ulcer (GU).

Helicobacter pylori (HP) infection alone, but not HP-induced atrophic gastritis, increases the risk of gastric lymphoma: a case-control study in Japan.

Infection with Helicobacter pylori (H. pylori) is associated with an increased risk of gastric malignant lymphoma. The chronic inflammation of gastric mucosa by H.

Salvage Haploidentical Transplantation Using Low-dose ATG for Early Disease Relapse after First Allogeneic Transplantation: A Retrospective Single-center Review.

Second allogeneic stem cell transplantation (allo-SCT) is a potentially curative therapy for patients who relapse after first allo-SCT. Human leukocyte antigen (HLA)-haploidentical related donors provide the broad opportunity to conduct second SCT at the appropriate time, but the efficacy of second SCT from haploidentical donors after relapse has not been established. We retrospectively analyzed the records of 33 patients who underwent second SCT.