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.
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. We also assessed the combined effect of pathogenic variants and
infection status on the risk of gastric cancer and calculated the cumulative risk in 1433 patients with gastric cancer and 5997 controls from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC).
Germline pathogenic variants in nine genes (
,
,
,
,
,
,
,
, and
) were associated with the risk of gastric cancer. We found an interaction between
infection and pathogenic variants in homologous-recombination genes with respect to the risk of gastric cancer in the sample from HERPACC (relative excess risk due to the interaction, 16.01; 95% confidence interval CI, 2.22 to 29.81; P = 0.02). At 85 years of age, persons with
infection and a pathogenic variant had a higher cumulative risk of gastric cancer than noncarriers infected with
(45.5% 95% CI, 20.7 to 62.6 vs. 14.4% 95% CI, 12.2 to 16.6).
infection modified the risk of gastric cancer associated with germline pathogenic variants in homologous-recombination genes. (Funded by the Japan Agency for Medical Research and Development and others.).
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. This study included 2,066 lymphoma patients and 38,153 cancer‐free controls from the Japanese population. Following quality control of sequencing data, samples from 1,982 lymphoma patients and 37,592 controls were further analyzed. We identified 309 pathogenic variants among 4,850 variants in the 27 cancer‐predisposing genes. Pathogenic variants in the following four cancer‐predisposing genes were associated with a high risk of lymphoma: ATM (odds ratio OR, 2.63; 95% confidence interval CI, 1.25–5.51; p = 1.06 × 10−2), BRCA1 (OR, 5.88; 95% CI, 2.65–13.02; p = 1.27 × 10−5), BRCA2 (OR, 2.94; 95% CI, 1.60–5.42; p = 5.25 × 10−4), and TP53 (OR, 5.22; 95% CI, 1.43–19.02; p = 1.23 × 10−2). The proportion of carriers of these genes was 1.6% of lymphoma patients. Furthermore, pathogenic variants in these genes were especially associated with a higher risk of mantle cell lymphoma (OR, 21.57; 95% CI, 7.59–61.26; p = 8.07 × 10−9). These results provide novel insights concerning monogenic form into lymphoma classification. Some lymphoma patients may benefit from surveillance and targeted treatment, such as other neoplasms.
We found that pathogenic variants in the four cancer‐predisposing genes (ATM, BRCA1, BRCA2, and TP53) were associated with lymphoma risk. Pathogenic variants in these genes were especially associated with a higher risk of mantle cell lymphoma. These results would provide novel insights concerning monogenic form into lymphoma classification.
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). Following these initial reports, however, few studies have since validated these associations. Here, we aimed to validate the association between variations in PSCA and the risk of DU/GU and evaluate its interaction with environmental factors in a Japanese population.
Six PSCA SNPs were genotyped in 584 DU cases, 925 GU cases, and 8,105 controls from the Japan Multi-Institutional Collaborative Cohort (J-MICC). Unconditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the SNPs and risk of DU/GU.
PSCA rs2294008 C-allele was associated with per allele OR of 1.34 (95% CI, 1.18-1.51; P = 2.28 × 10
) for the risk of DU. This association was independent of age, sex, study site, smoking habit, drinking habit, and H. pylori status. On the other hand, we did not observe an association between the risk of GU and PSCA SNPs.
Our study confirms an association between the PSCA rs2294008 C-allele and the risk of DU in a Japanese population.
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. Here, we assessed the trends in mortality rates of MM in parallel with incidence rates in Japan and the U.S. We used national mortality data and population‐based cancer registry data in both countries from 1995 to 2015, during which 74 972 patients in Japan and 229 290 patients in the U.S. died of MM. Trends in mortality and incidence rates were characterized using joinpoint regression analysis. Despite upward trends in incidence, mortality rates showed a significant decrement after 2005 in Japan, with an annual percent change APC (95% confidence interval) of −2.5% (−2.9% to −2.1%), and after 2002 in the U.S., with an APC of −2.0% (−2.6% to −1.5%). In both countries, the change in mortality trend coincided with the introduction of the novel agents. Moreover, improvements in mortality were particularly large in patients aged 70 to 79 years, who cannot receive ASCT. Our results indicate that the benefits of novel agents for MM are appreciable at the population level and may encourage further development of novel agents for malignancies that can be widely applied to the patients.
What's new?
Mortality rate is a key public health measure of progress against cancer and is sometimes markedly impacted by the approval of novel anticancer interventions. Here, the authors evaluated mortality and incidence rates of multiple myeloma (MM) in Japan and the United States, searching for trends associated with new therapeutic interventions. Their analyses show that mortality rates of MM decreased significantly after the introduction of novel therapies in the early 2000s, despite increasing trends in MM incidence rates in both countries. Mortality rates improved considerably among older patients, ages 70 to 79, who are unable to undergo autologous stem‐cell transplantation.
We describe a patient who presented with large cardiac diffuse large B-cell lymphoma (DLBCL) and adrenal masses. The patient also had subcutaneous intravascular lymphoma lesions which were detected ...by random skin biopsy. Although ambiguous, minimal extravascular location of lymphoma cells is permitted for the diagnosis of intravascular large B-cell lymphoma (IVLBCL) in the WHO definition, a number of rare cases have been reported as having concomitant tumours in other organs, such as the adrenal gland, brain, and penis. We assume that IVLBCL might be a peculiar feature of DLBCL characterised by preferential localisation of lymphoma cells within the capillaries rather than a distinct disease entity of DLBCL.
Background: Neurolymphomatosis (NL) is a rare pathological condition of non-Hodgkin lymphoma characterized by infiltration of malignant lymphoma cells into the peripheral nervous system. Patients may ...develop NL at initial presentation, during disease progression, or as relapse. Diagnosis is often difficult as clinical symptoms of NL are nonspecific and varied. Although nerve biopsy remains the gold standard for diagnosis, it is often unfeasible due to the possible irreversible neurological deficit and its scattered distribution. Prognosis and optimal therapeutic strategy are poorly understood due to its rarity. To clarify the clinical features of NL, we retrospectively analyzed 14 cases of NL with emphasis on diagnosis and treatment. This is a largest series of NL cases as a single institutional report.
Method: We reviewed the clinical records of patients admitted to our hospital from April 1, 2006, to April 30, 2016. Diagnosis of NL required: 1) clinical symptoms and neurological findings related to the peripheral nerves; and 2) histological confirmation of malignant lymphoma cells within these nerves; or 3) CT/MRI demonstration of nerve enhancement and/or enlargement of nerve(s) that were also demonstrated by accumulation of FDG on FDG-PET/CT and/or whole-body diffusion weighted whole-body MRI (DW-WBMRI). We surveyed therapeutic contents and analyzed prognosis.
Result: Over the past 10 years, 901 patients with NHL were admitted to our hospital; 14 patients (1.6%) were diagnosed with NL (7 men, 7 women, median age: 73.0 years, range: 60 - 84 years). Twelve patients were histologically diagnosed as DLBCL and 5 of them primarily presented with intravascular lymphoma (IVL). Among the 12 DLBCL patients, 8 were positive for CD5 (75.0%). One patient was originally diagnosed as mantle cell lymphoma (MCL), and another one patient was diagnosed as peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). NL occurred as part of primary disease in 3 patients and as relapse in the remaining 11 patients. All patients were diagnosed with NL by neurological findings and imaging studies (contrast-enhanced MRI, PET/CT, and/or DW-WBMRI). All of the patients with relapsed NL showed neither prominent lymphadenopathy nor abnormal laboratory data except neurological abnormalities. In one patient, NL lesions were evaluated by both PET/CT and DW-WBMRI simultaneously. DW-WBMRI had greater sensitivity for detecting NL lesions than PET/CT. Autopsy also confirmed lymphoma infiltration in one patient. Cerebrospinal fluid cytology was positive in 10 cases (71.4%).
Twelve patients received high-dose methotrexate (HD-MTX) in addition to systemic chemotherapy. Despite initial responses, rapid disease recurrence occurred in all patients. Neurological symptoms responded promptly in 7 of 8 patients receiving involved nerve irradiation (87.5%). Eleven patients (78.6%) died due to progressive NL. Three patients are still alive 109.0, 39.0 and 3.4 months, respectively, from the diagnosis of NL. The median survival after development of NL was 9.4 months (range: 1.0 - 109.0 months). Three patients received autologous stem cell transplantation (auto-SCT), 2 patients survived for more than 7 years free of disease and the other for 1 month just received transplantation, but the remaining one patient relapsed and died 4 months after auto-SCT.
Conclusion: NL is an extremely rare pathological condition (1.6%) and can present in diverse ways, both at initial diagnosis of lymphoma and after treatment. Twelve patients (85.7%) were DLBCL, and 75% of them were CD5-positive. IVL was the most common subtype. Cerebrospinal fluid was positive in 71.4% cases at the time of NL development. Imaging techniques, including contrast-enhanced MRI and PET/CT, are useful and DW-WBMRI may be more sensitive for detecting the relevant neural involvement. Prognosis remains poor once NL has developed despite the use of HD-MTX and rituximab-containing aggressive chemotherapy with or without auto-SCT. Only involved nerve irradiation was effective for temporary relief of neurological symptoms.
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No relevant conflicts of interest to declare.
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).
Methods
We retrospectively analyzed 130 patients who received their first allo-HSCT between April 2017 and December 2020, including 26 who received PTCY-haplo.
Results
The WT1 mRNA expression level at day + 30 after allo-HSCT associated with increased risk of 1-year cumulative incidence of relapse (CIR) was ≥ 78 copies/μg RNA in the conventional group (
p
< 0.01) and ≥ 50 copies/μg RNA in the PTCY-haplo group (
p
= 0.03).
Conclusions
The appropriate cutoff level of WT1 mRNA at day + 30 after allo-HSCT for predicting prognosis in patients treated with PTCY-haplo may be < 50 copies/μg RNA.
Abstract
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. Cigarette-use data were collected at each study baseline in 1983–1994. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality were calculated using multivariable-adjusted Cox regression by CPD among current smokers and by age at cessation among former smokers, with never smokers as the referent group. Pooled HRs and CIs were computed using a random-effect model.
Results
The smoking prevalence was 54.5% in men and 7.4% in women. About 15.5% of male and 50.4% of female current smokers smoked 1–10 CPD (low-intensity). Both male and female low-intensity smokers had higher all-cause mortality risks than never smokers. Risks were further higher with increasing CPD in a dose–response manner. HRs (95% CIs) were 1.27 (0.97–1.66), 1.45 (1.33–1.59) and 1.49 (1.38–1.62) for 1–2, 3–5 and 6–10 CPD, respectively, in men; 1.28 (1.01–1.62), 1.49 (1.34–1.66) and 1.68 (1.55–1.81) for 1–2, 3–5 and 6–10 CPD, respectively, in women. Similar associations were observed for smoking-related causes of death. Among former low-intensity smokers, younger age at cessation was associated with lower mortality risk.
Conclusions
Smoking very low amounts was associated with increased mortality risks in Japan. All smokers should quit, even if they smoke very few CPD.
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. Among them, 318 relapsed after first remission (REL) and 442 were refractory to the primary therapy (PIF). The 4-year overall survival (OS) of autoHCT and alloHCT was 50 and 50% for REL patients, and 52 and 49% for PIF patients, respectively. In the multivariable analysis, alloHCT tended to be associated with better progression-free survival (PFS) in REL (hazard ratio HR 0.74; 95% confidence interval CI: 0.53-1.03), and significantly better PFS in PIF (HR 0.64; 95% CI: 0.46-0.88) compared with autoHCT. The subgroup analysis with propensity-score matching showed that alloHCT was associated with better OS for REL-sensitive and PIF-nonremission disease. This study suggested that the advantage of alloHCT for R/R PTCL-NOS or AITL is different, depending on the disease status at HCT.
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