Risk Factor For Multiple Myeloma Research Articles

Risk Factors and the Effect of Antiviral Prophylaxis for Herpes Zoster in Multiple Myeloma Patients

To study the incidence and risk factors of herpes zoster in patients with multiple myeloma and to evaluate the preventive effect of antiviral therapy. The clinical features of multiple myeloma patients with herpes zoster were retrospectively analyzed, the risk factors of herpes zoster and the effect of antiviral prophylaxis were analyzed. Among 180 patients with multiple myeloma, 23 cases developed herpes zoster (12.8%). The incidence of herpes zoster was 19.1% in patients with renal dysfunction and 23.5% after autologous hematopoietic stem cell transplantation (ASCT). The incidence of herpes zoster was higher in patients receiving bortezomib-containing regimens (21/137, 15.3%) than that in those without bortezomib (2/43, 4.7%), but there was no statistical difference (P =0.067). Antiviral prophylaxis was associated with fewer zoster infections, 8/111(7.2%) developed herpes zoster in patients who received antiviral prophylaxis, and 15/69 (21.7%) in those receiving no prophylaxis(P =0.005). 65.2% of patients with herpes zoster did not receive antiviral prophylaxis. Multivariate analysis showed that bortezomib treatment, AHSCT and renal dysfunction were independent risk factors for multiple myeloma with herpes zoster, while antiviral prophylaxis was independently associated with reducing the risk of herpes zoster. Herpes zoster had no effect on OS in patients with multiple myeloma. The risk of herpes zoster in multiple myeloma patients was increased. Antiviral prophylaxis can reduce the risk of herpes zoster in patients on bortezomib-based therapy.

Pulmonary hemorrhage as a presentation of AL amyloidosis secondary to multiple myeloma: a case report

Abstract Background The convergence of pulmonary hemorrhage, pulmonary amyloidosis, and multiple myeloma is uncommon. Amyloidosis can affect the pulmonary parenchyma in a diffuse, tracheobronchial, or parenchymal pattern and may rarely be associated with pulmonary hemorrhage. Additionally, pulmonary amyloidosis is not a frequent manifestation of multiple myeloma. We present a case of a male patient with pulmonary hemorrhage as the initial manifestation of AL pulmonary amyloidosis, and ultimately, confirmation of multiple myeloma through bone marrow biopsy. Case presentation The clinical case involves a 60-year-old male with no significant medical history, who was admitted presenting a clinical picture evolving over 6 months characterized by hemoptoic cough, accompanied by dyspnea, a decrease in functional capacity, and constitutional symptoms. Thoracic CT images revealed multilobar ground-glass opacities with suspected alveolar hemorrhage. In response to this clinical presentation, bronchoalveolar lavage with cytology was performed, revealing the presence of hemosiderin-laden macrophages. Given the complexity of the case, further investigation included a wedge biopsy of the lung. The pathological report indicated an atypical lymphoplasmacytoid proliferation with deposits of eosinophilic amorphous material, suggestive of amyloidosis. Congo red staining confirmed the presence of amyloid material. Elevated Kappa light chains were detected in both serum and urine, with an increased K/L ratio. Immunoglobulins G and M were found to be decreased. As part of the comprehensive assessment, a bone marrow biopsy was conducted, confirming the diagnosis of multiple myeloma with 10% atypical plasma cells. In light of this diagnosis, appropriate treatment has been initiated to address this intricate medical condition effectively. Conclusion The present case report provides an illustrative perspective on an uncommon presentation of pulmonary amyloidosis secondary to multiple myeloma, with the initial manifestation being pulmonary hemorrhage. The findings from both the physical examination and laboratory tests were consistent with pulmonary amyloidosis, and definitive confirmation of the multiple myeloma diagnosis was achieved through bone marrow biopsy. This case highlights the significance of considering pulmonary amyloidosis as a potential cause of hemoptysis, especially in patients with associated risk factors for multiple myeloma. Early recognition of this clinical association is pivotal for precise diagnosis and prompt therapeutic intervention. The complexity of this case underscores the importance of a comprehensive diagnostic approach in unraveling intricate medical conditions.

Body size and risk of multiple myeloma in the Black Women's Health Study.

Obesity is an established risk factor for multiple myeloma (MM). Relatively few prior studies, however, have evaluated associations in Black populations. Among 55,276 participants in the Black Women's Health Study, a prospective U.S. cohort established in 1995, we confirmed 292 incident diagnoses of MM over 26 years of follow-up. Multivariable Cox proportional hazard models, adjusted for age and putative MM risk factors, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of usual body mass index (BMI), BMI at age 18, height, and waist-to-hip ratio with MM. Compared to women with a usual adult BMI < 25 kg/m2, the HR associated with a usual adult BMI ≥ 35 kg/m2 was 1.38 (95% CI: 0.96, 1.98). For early adult BMI, the HR comparing women with BMI ≥ 25 vs. <25 kg/m2 was 1.57 (95% CI: 1.08, 2.28). Women who were heavy in both early and later life had the highest risk compared to those who were lean at both time points (HR: 1.60; 95% CI: 1.02, 2.52). Height was also associated with the risk of MM; the HR per 10 cm was 1.21 (95% CI: 1.02, 1.43). These results indicate that high early adult BMI is associated with a 57% increased risk of MM in Black women and potentially highlight the importance of weight control as a preventive measure.

A study to identify novel biomarkers associated with multiple myeloma

Background. multiple myeloma (mm) is a plasma cell cancer that affects white blood cells. plasma cells from the bone marrow grow abnormally, as a consequence of which patients have high amounts of monoclonal immunoglobulin in their blood and urine, poor renal function, and recurring infections due to this condition. osteolytic bone lesions and immunodeficiency also impact multiple myeloma patients’ longevity and quality of life. The disease accounts for 13 % of all hematological malignancies worldwide, making it the second most common blood cancer.Material and Methods. The studies investigating mm biomarkers from 2000 to 2021 are collected from various databases. “multiple myeloma”, “biomarkers”, “genetic markers”, “prognostic markers”, “epidemiology of multiple myeloma”, and “risk factors for multiple myeloma” are the key phrases utilized to gather the articles.Results. The scientific and medical research progressed into mm, and the number of cases increased over time and continues to rise, prompting researchers and clinicians to discover new consequences of the disease and new markers for prognosis, diagnosis, detection, and treatment of cancer in the earliest stages. Prognostic and predictive signs for illness recurrence and response to medication may be detected adequately by innovative potential biomarkers, which are more accurate than current approaches.Conclusion. treatment for multiple myeloma includes a variety of chemotherapeutic medicines, including immune modulators and proteasome inhibitors; however, most patients still experience recurrence after completing treatment. There have been numerous novel techniques for managing multiple myeloma, and this review summarises the most commonly used and the new ones that have appeared in the previously published articles.

The obesity paradox in multiple myeloma: A report from Multiple Myeloma Research Foundation (MMRF) dataset.

Obesity is a risk factor for multiple myeloma (MM). However, we still lack knowledge on the clinical course of obese MM patients in a broad view. Here, we reviewed 568 MM patients recorded in the Multiple Myeloma Research Foundation (MMRF) coMMpass dataset. Patients were divided into the normal and obese groups according body mass index (BMI) at diagnosis, and then the baseline characteristics, cytogenetic abnormalities, treatment variability, and survival outcomes were evaluated in the obese cohort. We found no differences in the characteristics when comparing normal and obese MM patients other than more male in the obese part (50.4% vs. 59.9%, p = 0.024). Compared with the normal BMI patients, median overall survival (OS) was shorter for obese MM patients but without significant meaning (82.3 vs. 95.3 months, p = 0.25). However, in the subgroup analysis, obese MM patients younger than 65 years had significantly inferior OS than that in the normal category (p = 0.047). We also found obese MM patients had a higher overall response rate (ORR) compared with normal BMI patients (92.7% vs. 88.6%, p = 0.037). Additionally, obese patients seemed to achieve faster best response during first-line therapy. Obesity assumes a paradoxical function in the clinical trajectory of myeloma.

Exposure to Fine Particulate Matter (PM2.5) Is Associated with Worse Multiple Myeloma Outcomes in a Large, Urban, Multi-Ethnic Cohort

Introduction Outdoor air pollution (OAP) is a complex mixture, primarily consisting of black carbon (BC), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter with an aerodynamic diameter of less than 2.5 microns (PM2.5). OAP is typically generated by the combustion process from motor vehicles, fossil fuel burning and industrial waste. The potential impact of air pollutants on cancer outcomes has not been systematically studied in communities of color. Multiple Myeloma (MM) is a hematologic malignancy defined by the clonal expansion of plasma cells leading to subsequent monoclonal protein expression resulting in multiple complications including anemia, renal disease, significant bone pain and increased fracture risk. MM is the second most common hematologic malignancy. The US Surveillance, Epidemiology, and End Results (SEER) registry estimates 34,000 new cases diagnosed and 13,000 deaths annually from MM. Risk factors for multiple myeloma include race, BMI, and occasionally genetic predisposition. Blacks and Hispanics were shown to have a higher incidence of MM that of non-Hispanic whites (Kaur G et al Clin Lymphoma Myeloma Leuk. 2021). There is recent evidence to suggest that environmental exposures, OAP in particular, may play a role in propagating disease progression in multiple myeloma (Landgren O JAMA Oncol 2015). A recent study demonstrated that first responders to the World Trade Center disaster had a higher rate of developing myeloma precursor disease (MGUS) and an earlier age of developing multiple myeloma (Landgren O JAMA Oncol. 2018). Our study seeks to further characterize patterns of exposure to OAP in patients with MM. Methods A retrospective cohort was developed of patients diagnosed with Multiple Myeloma at Montefiore Health System (Bronx, NY) between 1997-2018 (n=1608), using the Montefiore Electronic Data Warehouse. Of those patients, 1525 were identified as having 1 st cancer diagnosis of MM. Patient addresses (n=1514) were then used to geospatially overlay with OAP and Organic Matter from 2000-2018 using land use regression models. Ground-level PM2.5 was estimated by combining Aerosol Optical Depth (AOD) retrievals from the NASA MODIS, MISR, and SeaWIFS instruments with the GEOS-Chem chemical transport model, and subsequently calibrated to regional ground-based observations of both total and compositional mass using Geographically Weighted Regression (Hammer M.S et al Environ. Sci. Technol. 2020). This initial analysis focuses specifically on PM2.5, which was summarized as the number of years each patient was exposed to levels higher than the EPA standard of 12ug/m 3 and if the patient experienced an average PM2.5 &amp;gt;12ug/m 3 across their entire follow-up in the cohort. Additional information regarding demographics, dates of diagnosis and certain clinical parameters (Hgb, Cr, albumin, etc) were extracted. Differences in PM2.5 exposures, and clinical parameters, were compared by race and ethnicity using t-tests and chi-squared tests. Cox proportional hazards regression estimated the risk of death during follow-up associated with PM2.5 exposure, adjusting for confounders. Results Our patient population was highly diverse. Patients were 21% White, 50% Black with 27% having Race classified as Other. Thirty percent were Hispanic. Age at mean diagnosis was 66.24 years. On average, Bronx MM patients had higher exposure to PM2.5 than the EPA safe standard of 12 µg/m 3 from years 2000-2007 and the WHO safe standard of 5 µg/m 3 in all years of follow-up. Improved overall survival among our Multiple Myeloma patients was associated with fewer number of years exposed to PM2.5 &amp;gt;12 µg/m 3 (Hazard Ratio (HR)=1.12, 95% Confidence Interval (CI)=0.99- 1.27), when adjusting for sex and race. Further adjustment for smoking status yielded similar results (HR = 1.13, 95%CI = 0.98-1.30). Conclusion In this large urban, multi-ethnic cohort of MM patients, many patients experienced annual exposures to PM2.5 that were higher than the EPA and WHO safe standards of 12 µg/m 3 and 5 µg/m 3. Overall survival in MM patients was associated with fewer years of exposure to PM2.5, suggesting that reducing exposure to environmental pollutants, particularly OAP for our patients may lead to better outcomes. Additional analyses are needed to better understand the impact of treatment and clinical factors, as well as the other air pollutants in this patient population.

Non-Toxicological Role of Aryl Hydrocarbon Receptor in Obesity-Associated Multiple Myeloma Cell Growth and Survival.

Obesity is not only a risk factor for multiple myeloma (MM) incidence, but it is also associated with an increased risk of progression from myeloma precursors-monoclonal gammopathy of undetermined significance-and smoldering myeloma. Adipocytes in the bone marrow (BMAs) microenvironment have been shown to facilitate MM cell growth via secreted factors, but the nature of these secreted factors and their mechanism of action have not been fully elucidated. The elevated expression of aryl hydrocarbon receptor (AhR) is associated with a variety of different cancers, including MM; however, the role of AhR activity in obesity-associated MM cell growth and survival has not been explored. Indeed, this is of particular interest as it has been recently shown that bone marrow adipocytes are a source of endogenous AhR ligands. Using multiple in vitro models of tumor-adipocyte crosstalk to mimic the bone microenvironment, we identified a novel, non-toxicological role of the adipocyte-secreted factors in the suppression of AhR activity in MM cells. A panel of six MM cell lines were cultured in the presence of bone marrow adipocytes in (1) a direct co-culture, (2) a transwell co-culture, or (3) an adipocyte-conditioned media to interrogate the effects of the secreted factors on MM cell AhR activity. Nuclear localization and the transcriptional activity of the AhR, as measured by CYP1A1 and CYP1B1 gene induction, were suppressed by exposure to BMA-derived factors. Additionally, decreased AhR target gene expression was associated with worse clinical outcomes. The knockdown of AhR resulted in reduced CYP1B1 expression and increased cellular growth. This tumor-suppressing role of CYP1A1 and CYP1B1 was supported by patient data which demonstrated an association between reduced target gene expression and worse overall survival. These data demonstrated a novel mechanism by which bone marrow adipocytes promote MM progression.

Unlocking Drug Resistance in Multiple Myeloma: Adipocytes as Modulators of Treatment Response.

Multiple myeloma (MM) is an incurable hematological malignancy characterized by the clonal proliferation of malignant plasma cells. Despite the development of a diverse array of targeted drug therapies over the last decade, patients often relapse and develop refractory disease due to multidrug resistance. Obesity is a growing public health threat and a risk factor for multiple myeloma, although the mechanisms by which obesity contributes to MM growth and progression have not been fully elucidated. In the present study, we evaluated whether crosstalk between adipocytes and MM cells promoted drug resistance and whether this was amplified by obesity. Human adipose-derived stem cells (ASCs) from nineteen normal (BMI = 20-25 kg/m2), overweight (25-30 kg/m2), or obese (30-35 kg/m2) patients undergoing elective liposuction were utilized. Cells were differentiated into adipocytes, co-cultured with RPMI 8226 or U266B1 multiple myeloma cell lines, and treated with standard MM therapies, including bortezomib or a triple combination of bortezomib, dexamethasone, and lenalidomide. We found that adipocytes from overweight and obese individuals increased cell adhesion-mediated drug resistance (CAM-DR) survival signals in MM cells, and P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) drug transporter expression. Further, co-culture enhanced in vitro angiogenesis, MMP-2 activity, and protected MM cells from drug-induced decreases in viability. In summary, we provide an underlying mechanism by which obesity can impair the drug response to MM and allow for recurrence and/or disease progression.

Obesity as a risk factor for multiple myeloma: insight on the role of adipokines.

Multiple myeloma (MM) is a hematologic disorder characterized by the accumulation of malignant plasma cells in the bone marrow. Genetic and environmental factors are contributed to the etiology of MM. Notably, studies have shown that obesity increases the risk of MM and worsens outcomes for MM patients. Adipokines play an important role in mediating the close association between MM and metabolic derangements. In this review, we summarize the epidemiologic studies to show that the risk of MM is increased in obese. Accumulating clinical evidence suggests that adipokines could display a correlation with MM. In vitro and in vivo studies have shown that adipokines are linked to MM, including roles in the biological behavior of MM cells, cancer-associated bone loss, the progression of MM, and drug resistance. Current and potential therapeutic strategies targeted to adipokines are discussed, proposing that adipokines can guide early patient diagnosis and treatment.

The Association between Body Mass Index Trajectory and the Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma

Background: Obesity is a known risk factor for multiple myeloma (MM), as prior studies have shown that body mass index (BMI) greater than 25 kg/m2 (at a fixed time point) increases the risk for MM and its premalignant condition, monoclonal gammopathy of undetermined significance (MGUS). However, to date, no studies have evaluated whether changes in BMI over time affect the progression of MGUS to MM. We aimed to assess the association between changes in BMI following a diagnosis of MGUS and the progression of MGUS. Methods: Patients with MGUS from 1999-2021 in the Veterans Health Administration were identified. We used a natural language processing (NLP) based algorithm to confirm MGUS diagnosis and progression, including smoldering MM and MM. Only patients with IgG, IgA, or light chain MGUS and black and white patients were included in the analyses. Patients with Diabetes Mellitus (DM) were excluded from analysis due to potential confounding bias. Patients who progressed within 5 years of MGUS diagnosis were also excluded. Excess BMI was defined as BMI over 25 kg/m2. To capture the trajectory of excess BMI, the area under the curve (AUC) of excess BMI during the 5 years following MGUS diagnosis was calculated. A multivariable time-to-competing-event analysis was performed to estimate the multivariable-adjusted association of AUC of excess BMI with progression with death as the competing event. The covariates included BMI at MGUS diagnosis, M-protein level (>= 1.5g/dL), age at MGUS diagnosis, sex, race, MGUS heavy chain subtype, light-chain MGUS. Results: After applying our inclusion and exclusion criteria, our analytic cohort included 7,739 MGUS patients. Our multivariable time-to-competing-event analysis revealed a positive association between excess BMI trajectory and MM progression (multivariable-adjusted hazard ratio, aHR, 1.02, 95% confidence interval, CI, 1.01-1.03) - a 2% increase in risk of progression per 1 kg/m2 increase in excess BMI per year following MGUS diagnosis. Conclusion: In patients diagnosed with MGUS, increases in excess BMI by 1 kg/m2 per year were associated with 2% increased risk of progression to MM. This finding suggests that maintaining a healthy weight in patients with MGUS may reduce the risk of progression. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Anthropometric traits and risk of multiple myeloma: a pooled prospective analysis.

Obesity is a risk factor for multiple myeloma (MM), yet results of prior studies have been mixed regarding the importance of early and/or later adult obesity; other measures of body composition have been less wellstudied. We evaluated associations of early adult (ages 18-21) and usual adult body mass index (BMI), waist circumference, and predicted fat mass with MM by pooling data from six U.S. prospective cohort studies comprising 544,016 individuals and 2756 incident diagnoses over 20-37 years of follow-up. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations, adjusted for age and other risk factors. Each 5 kg/m2 increase in usual adult BMI was associated with a 10% increased risk of MM (HR: 1.10; 95% CI: 1.05-1.15). Positive associations were also noted for early adult BMI (HR per 5 kg/m2: 1.14; 95% CI: 1.04-1.25), height (HR per 10 cm: 1.28; 95% CI: 1.20-1.37), waist circumference (HR per 15 cm: 1.09; 95% CI: 1.00-1.19), and predicted fat mass (HR per 5 kg: 1.06; 95% CI: 1.01-1.11). These findings highlight the importance of avoidance of overweight/obesity and excess adiposity throughout adulthood as a potential MM risk-reduction strategy.

Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria

BackgroundGut microbiome alterations are closely related to human health and linked to a variety of diseases. Although great efforts have been made to understand the risk factors for multiple myeloma (MM), little is known about the role of the gut microbiome and alterations of its metabolic functions in the development of MM.ResultsHere, in a cohort of newly diagnosed patients with MM and healthy controls (HCs), significant differences in metagenomic composition were discovered, for the first time, with higher bacterial diversity in MM. Specifically, nitrogen-recycling bacteria such as Klebsiella and Streptococcus were significantly enriched in MM. Also, the bacteria enriched in MM were significantly correlated with the host metabolome, suggesting strong metabolic interactions between microbes and the host. In addition, the MM-enriched bacteria likely result from the regulation of urea nitrogen accumulated during MM progression. Furthermore, by performing fecal microbiota transplantation (FMT) into 5TGM1 mice, we proposed a mechanistic explanation for the interaction between MM-enriched bacteria and MM progression via recycling urea nitrogen. Further experiments validated that Klebsiella pneumoniae promoted MM progression via de novo synthesis of glutamine in mice and that the mice fed with glutamine-deficient diet exhibited slower MM progression.ConclusionsOverall, our findings unveil a novel function of the altered gut microbiome in accelerating the malignant progression of MM and open new avenues for novel treatment strategies via manipulation of the intestinal microbiota of MM patients.Ef13dgTkxr8yaT6cBDYXQ2Video abstract.

Association between diabetes mellitus, hypertension, hyperlipidemia, chronic viral hepatitis, and the risk of multiple myeloma: a case-control study

Abstract Objective This case-control study aimed to investigate whether diabetes mellitus (DM), hypertension, hyperlipidemia, and chronic viral hepatitis are risk factors for multiple myeloma (MM). Moreover, the clinical characteristics of MM patients with or without the abovementioned exposure factors were analyzed. Methods In total, 340 MM patients and 680 patients with benign diseases who were hospitalized from January 2012 to December 2017 were classified under the case group and control group, respectively. Data about medical history of DM, hypertension, hyperlipidemia and chronic viral hepatitis were collected by reviewing medical records. Univariate and multivariate analyses were conducted to compare the history of DM, hypertension, hyperlipidemia, and viral hepatitis between the two groups. Considering DM, hypertension, hyperlipidemia, and chronic viral hepatitis as exposure factors, clinical characteristics, such as renal function and presence of fungal and other types of infections, between the exposed and non-exposed groups were analyzed. Results No significant difference was observed in the prevalence of DM, hypertension, and hyperlipidemia between the case and control groups. MM patients had a higher prevalence of chronic viral hepatitis than those with benign diseases. No significant difference was observed in the prevalence of renal dysfunction, fungal infection, and non-fungal infections in MM patients with or without DM, hypertension, and hyperlipidemia. MM patients with chronic viral hepatitis had a significantly higher prevalence of non-fungal infections during hospitalization than those without. Conclusion No significant association was noted between MM and DM, hypertension, and hyperlipidemia. Chronic viral hepatitis is correlated to a significantly higher risk of MM, and MM patients with chronic viral hepatitis were more susceptible to non-fungal infections during hospitalization. Although a non-significant trend was observed in this study, we believe that DM and hypertension might be associated with a higher risk of MM. Thus, large-scale studies must be conducted to validate the results of the current study.

Alterations of Gut Microbiome Accelerate Multiple Myeloma Progression By Increasing the Relative Abundances of Nitrogen Recycling Bacteria

Background: Gut microbiome alterations are closely related to human health and linked to a variety of diseases. Although great efforts have been made to understand the risk factors for multiple myeloma (MM), little is known about the role of the gut microbiome and alterations of its metabolic functions in the development of MM patients. Materials and Methods: From a cohort of 19 newly diagnosed patients with MM and 18 gender- and age-matched healthy controls (HCs), fresh fecal samples and fasting serum samples were collected, respectively, for metagenomic sequencing and metabolomic detection. Subsequently, the high-quality reads were used for taxonomic classification using Kraken and for functional annotation using MetaCV, and metabolic profiling was statistically analyzed using SIMCA-P. On the R platform, bacterial diversity was analyzed using vegan package and differential taxa were identified using DESeq2 package. In addition, we performed fecal microbiota transplantation (FMT) experiments in C57BL/KaLwRij mice which can be artificially induced to develop MM by injecting 5TGM1 MM cells. Results: Here, significant differences in bacterial composition between MM and HC were first discovered (PERMANOVA, P=0.001), and greater bacterial richness in MM was evaluated by Shannon index (P=0.045). Several species with significant difference between the two groups were further confirmed by using qPCR of 16S rDNA V1-V2 regions in an expend cohort. Specifically, short-chain-fatty-acid producing bacteria such as Clostridium butyrate were substantially shrunk, while nitrogen recycling bacteria such as Klebsiella sp. were significantly enriched in MM. And, the MM-enriched bacteria showed higher abundance in MM patients with ISS-Ⅲ than those of MM patients with ISS-Ⅱ. We measured much more urea in the serum of MM than those in HC (P&amp;lt;0.001). Meanwhile, the MM-enriched bacteria were significantly correlated to the differential metabolites in host serum, suggesting strong metabolic interactions between microbes and the host. The MM-enriched bacteria were also considered to cause the enhanced urease (URE, P=0.016) and glutamine synthase activities (GS, P=0.015). To investigate the function of the microbe-host interactions in MM progression, we performed FMT experiments in C57BL/KaLwRij mice with MM and HC feces suspension (three groups: FMT_MM, FMT_HC, PBS). As a result, we observed faster MM progression in FMT_MM mice and slower MM progression in FMT_HC mice than that of PBS mice. Notably, much more L-glutamine (Gln) in the bone marrow of FMT_MM mice was detected (FMT_MM=2.07±0.04 mM, FMT_HC=1.23±0.10 mM, PBS=1.33±0.09 mM, P&amp;lt;0.05). With one accord, more Gln was also measured in the serum and cecum of FMT_MM mice. Therefore, we speculated that MM-enriched bacteria efficiently hydrolyze urea to de novo synthesize Gln, which may accelerate MM development. Indeed, in the cecum contents of FMT_MM mice, more urea and higher URE and GS activities were all detected (P&amp;lt;0.05). Moreover, the accumulating urea was probably due to the declining renal function, as the experimental mice all exhibit more protein deposition of IgG2b kappa on the renal tubules than that of normal mice. Particularly, FMT_MM mice had the highest amount of IgG2b kappa, followed by FMT_HC mice and PBS mice (OD: FMT_MM=0.15±0.02, FMT_HC=0.08±0.02, PBS=0.09±0.02, Normal=0.04±0.00, P&amp;lt;0.05). Further, we performed additional experiments by gavage, and the results validated that the increase of Klebsiella pneumoniae abundance accelerated MM progression in vivo, while Clostridium butyrate had an opposite effect. Conclusions: Taken together, we showed that the gut microbiome in MM patients played an active role in malignant progression and that the microbe-host interactions were predominantly involved in nitrogen recycling and utilization in MM, which open new avenues for MM treatment via monitoring and manipulation of intestinal flora. Furthermore, these findings lead us to propose a broad mechanism, in which the increasing urea or NH4+ alters the gut bacterial composition, leading to preferential accumulation of nitrogen-recycling bacteria and suppression of the bacteria producing short-chain fatty acids. The altered gut microbiome should be conducive to nitrogen recycling and utilization by the host-microbe superorganism. Disclosures No relevant conflicts of interest to declare.

Comprehensive Investigation of White Blood Cell and Gene Expression Profiles As Risk Factors for Multiple Myeloma in African Americans

Comprehensive Investigation of White Blood Cell and Gene Expression Profiles As Risk Factors for Multiple Myeloma in African Americans

Association of BMI, Smoking, and Alcohol with Multiple Myeloma Mortality in Asians: A Pooled Analysis of More than 800,000 Participants in the Asia Cohort Consortium.

To date, few epidemiologic studies have been conducted to elucidate lifestyle-related risk factors for multiple myeloma in Asia. We investigated the association of body mass index (BMI), smoking, and alcohol intake with the risk of multiple myeloma mortality through a pooled analysis of more than 800,000 participants in the Asia Cohort Consortium. The analysis included 805,309 participants contributing 10,221,623 person-years of accumulated follow-up across Asia Cohort Consortium cohorts. HRs and 95% confidence intervals (95% CI) for the association between BMI, smoking, and alcohol at baseline and the risk of multiple myeloma mortality were assessed using a Cox proportional hazards model with shared frailty. We observed a statistically significant dose-dependent association between BMI categories and the risk of multiple myeloma mortality (<18.5 kg/m2: HR = 0.80, 95% CI: 0.52-1.24; 18.5-24.9 kg/m2: reference; 25.0-29.9 kg/m2: HR = 1.17, 95% CI: 0.94-1.47; ≥30 kg/m2: HR = 1.61, 95% CI: 0.99-2.64, P trend = 0.014). By sex, this association was more apparent in women than in men (P for heterogeneity between sexes = 0.150). We observed no significant associations between smoking or alcohol consumption and risk of multiple myeloma mortality. This study showed that excess body mass is associated with an increased risk of multiple myeloma mortality among Asian populations. In contrast, our results do not support an association between smoking or alcohol consumption and the risk of multiple myeloma mortality in Asian populations. This study provides important evidence on the association of BMI, smoking, and alcohol with the risk of multiple myeloma mortality in Asian populations.

Elucidating Under-Studied Aspects of the Link Between Obesity and Multiple Myeloma: Weight Pattern, Body Shape Trajectory, and Body Fat Distribution.

BackgroundAlthough obesity is an established modifiable risk factor for multiple myeloma (MM), several nuanced aspects of its relation to MM remain unelucidated, limiting public health and prevention messages.MethodsWe analyzed prospective data from the Nurses’ Health Study and Health Professionals Follow-Up Study to examine MM risk associated with 20-year weight patterns in adulthood, body shape trajectory from ages 5 to 60 years, and body fat distribution. For each aforementioned risk factor, we report hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MM from multivariable Cox proportional-hazards models.ResultsWe documented 582 incident MM cases during 4 280 712 person-years of follow-up. Persons who exhibited extreme weight cycling, for example, those with net weight gain and one or more episodes of intentional loss of at least 20 pounds or whose cumulative intentional weight loss exceeded net weight loss with at least one episode of intentional loss of 20 pounds or more had an increased MM risk compared with individuals who maintained their weight (HR = 1.71, 95% CI = 1.05 to 2.80); the association was statistically nonsignificant after adjustment for body mass index. We identified four body shape trajectories: lean-stable, lean-increase, medium-stable, and medium-increase. MM risk was higher in the medium-increase group than in the lean-stable group (HR = 1.62, 95% CI = 1.22 to 2.14). Additionally, MM risk increased with increasing hip circumference (HR per 1-inch increase: 1.03, 95% CI = 1.01 to 1.06) but was not associated with other body fat distribution measures.ConclusionsMaintaining a lean and stable weight throughout life may provide the strongest benefit in terms of MM prevention.

Chronic intermittent hypoxia enhances disease progression in myeloma-resistant mice.

Obesity is the only known modifiable risk factor for multiple myeloma (MM), an incurable cancer of bone marrow plasma cells. The mechanism linking the two is unknown. Obesity is associated with an increased risk of sleep apnea, which results in chronic intermittent hypoxia (CIH), and drives solid tumor aggressiveness. Given the link between CIH and solid tumor progression, we tested the hypothesis that CIH drives the proliferation of MM cells in culture and their engraftment and progression in vivo. Malignant mouse 5TGM1 cells were cultured in CIH, static hypoxia, or normoxia as a control in custom, gas-permeable plates. Typically MM-resistant C57BL/6J mice were exposed to 10 h/day CIH (AHI = 12/h), static hypoxia, or normoxia for 7 days, followed by injection with 5TGM1 cells and an additional 28 days of exposure. CIH and static hypoxia slowed the growth of 5TGM1 cells in culture. CIH-exposed mice developed significantly more MM than controls (67 vs. 12%, P = 0.005), evidenced by hindlimb paralysis, gammopathy, bone lesions, and bone tumor formation. Static hypoxia was not a significant driver of MM progression and did not reduce survival (P = 0.117). Interestingly, 5TGM1 cells preferentially engrafted in the bone marrow and promoted terminal disease in CIH mice, despite a lower tumor burden, compared with the positive controls. These first experiments in the context of hematological cancer demonstrate that CIH promotes MM through mechanisms distinct from solid tumors and that sleep apnea may be a targetable risk factor in patients with or at risk for blood cancer.

Regions of homozygosity as risk factors for multiple myeloma.

Genomic regions of homozygosity (ROH), detectable in outbred populations, have been implicated as determinants of inherited risk. To examine whether ROH is associated with risk of multiple myeloma (MM), we performed whole‐genome homozygosity analysis using single‐nucleotide polymorphism genotype data from 2,282 MM cases and 5,197 controls, with replication in an additional 878 MM cases and 7,083 controls. Globally, the distribution of ROH between cases and controls was not significantly different. However, one ROH at chromosome 9q21, harboring the B‐cell transcription factor gene KLF9, showed evidence of a consistent association and may therefore warrant further investigation as a candidate risk factor for MM. Overall, our analysis provides little support for a homozygosity signature being a significant factor in MM risk.

A systematic analysis of multiple myeloma and the related risk of HBV and HCV infection

Objective This study aimed to assess the risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients with multiple myeloma (MM) by systematic analysis. Methods The literature was retrieved in 4 English databases (PubMed, Web of science, OVID, Cochrane Library) and 3 Chinese databases (CNKI, VIP, and Wanfang) as of september 2016. The key word in English/ Chinese database retrieval is MM or multiple myeloma and infection . Newcastle Ottawa Scale (NOS) was used to evaluate the article quality. The overall odds ratio (OR) and 95% confidence intervals (95% CIs) were estimated by fixed (heterogeneity test at I2<25%) or random (heterogeneity test at I2≥25%) effects model. Results A total of 9 studies were included in the Meta analysis. The study found that multiple myeloma patients had an increased risk of HBV and HCV infection, 3.17 and 4.16 times higher than the control group. HBV (OR=3.17, 95% CI: 1.17-1.96, I2=27%, P=0.002) and HCV (OR=4.16, 95% CI: 1.33-2.22, I2=0%, P<0.001) in the multiple myeloma group were significantly different from those of the control group (P<0.05). Conclusions HBV and HCV are risk factors for multiple myeloma and should be highly regarded and controlled before and after treatment. Key words: Multiple myeloma/CO; Hepatitis B/CO; Hepatitis C/CO; Meta-analysis