Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesAll multiple myeloma (MM) cases are preceded by the premalignant state monoclonal gammopathy of undetermined significance (MGUS). Results from previous studies show a positive association between obesity and MM; however, the association between obesity and MGUS is controversial. The aims were to determine (1) if obesity is associated with an increased risk of MGUS and light-chain MGUS (LC-MGUS) and (2) whether obesity is associated with a higher risk of progression to MM and other lymphoproliferative (LP) diseases. Data from the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (N = 5764) were used. We performed serum protein electrophoresis and serum free light-chain assay on all subjects to identify MGUS and LC-MGUS cases. We included 11 different measures on current and previous obesity in our analysis. Logistic regression and Cox proportional-hazard regression were used to analyze the associations. A total of 300 (5.2%) MGUS and 275 (4.8%) LC-MGUS cases were identified. During a median follow-up of 8 years, 18 had progressed to MM and 11 to other LP diseases. We found no association between the 11 obesity markers and MGUS or LC-MGUS (odds ratios 0.81 to 1.15 for all 11 variables in both conditions). Interestingly, we found that high midlife body mass index increased risk of progression to MM and other LP diseases (hazard ratio, 2.66; 95% confidence interval, 1.17-6.05). To conclude, obesity was not associated with MGUS. However, we found overweight/obesity to be a risk factor for progression from MGUS to MM and other LP diseases, suggesting that obesity plays a role in the transformation of MGUS to MM.National Institutes of Health, National Institute on Aging National Institute on Aging Intramural Research Program, a National Eye Institute Intramural Research Program Award National Institute on Deafness and Other Communication Disorders, Division of Scientific Programs Hjartavernd (the Icelandic Heart Association) Althingi (the Icelandic Parliament) University of Iceland Research Fund Icelandic Centre for Research (RANNIS) Landspitali University Hospital Research Fund Karolinska Instituted Foundations Marie Curie CIG National Cancer Institute, National Institutes of Healt

Bone disease in monoclonal gammopathy of undetermined significance: results from a screened population-based study

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesPrevious studies have shown that individuals with monoclonal gammopathy of undetermined significance (MGUS) have an increased risk of fractures, although the underlying mechanisms remain unknown. Our aim was to analyze bone mineral density (BMD), bone volume, and risk of fractures among individuals with MGUS. We performed a screening using the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study cohort, consisting of 5764 elderly individuals, identifying 300 individuals with MGUS, and 275 with light-chain MGUS. Quantitative computerized tomography was performed in the lumbar spine and hip to evaluate BMD and bone geometry. Analysis of variance and the Tukey honest significance test were used to compare the groups. Hospital records were used to record fractures, with a mean follow-up of 6.9 years. Cox proportional hazard was used to compare fracture risk. No difference was found in BMD between subjects with MGUS and others in the spine (P = .34) or in total hip (P = .30). Individuals with MGUS had a significant increase in bone volume compared with others in the spine (P < .001) and total hip (P < .001). Overall, the risk of fractures was not significantly increased in individuals with MGUS (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.94-1.50). Men with MGUS had a significantly increased fracture risk, compared with other men (HR, 1.46; 95% CI, 1.03-2.08). Our results show that although individuals with MGUS do not have decreased BMD, bone volume is increased, and MGUS men have a 50% increased fracture risk. These results indicate that bone disease and fractures in MGUS differ from processes known from osteoporosis.University of Iceland Research Fund Icelandic Centre for Research (RANNIS) Landspitali University Hospital Research Fund Karolinska Institutet Foundations Marie Curie Career Integration Grants (CIG) National Institutes of Health, National Institute on Aging (NIA) NIA Intramural Research Program National Eye Institute National Institute on Deafness and Other Communication Disorders Division of Scientific Programs, Hjartavernd Althingi (the Icelandic Parliament) National Cancer Institute Memorial Sloan Kettering Cancer Center Icelandic National Bioethics Committe

Dietary intake is associated with risk of multiple myeloma and its precursor disease

Publisher's version (útgefin grein)The etiology of monoclonal gammopathy of undetermined significance (MGUS), the precursor state of multiple myeloma (MM), is mostly unknown and no studies have been conducted on the effect of diet on MGUS or progression from MGUS to MM. We aimed to explore the association between common foods and MGUS and progression to MM. Data from the population-based AGES Study (N = 5,764) were utilized. Food frequency questionnaire was used to assess dietary intake during adolescence, midlife, and late life. Serum protein electrophoresis and serum free light-chain assay was performed to identify MGUS (n = 300) and LC-MGUS cases (n = 275). We cross linked our data with the Icelandic Cancer Registry to find cases of MM in the study group. We found that intake of fruit at least three times per week during adolescence was associated with lower risk of MGUS when compared to lower fruit consumption (OR = 0.62, 95% CI 0.41–0.95). We additionally found that intake of fruit at least three times per week during the late life period was associated with decreased risk of progressing from MGUS to MM (HR = 0.34, 95% CI 0.13–0.89) when compared to lower intake. Adolescent intake of fruit may reduce risk of MGUS, whereas fruit intake after MGUS onset may reduce risk of progressing to MM. Our findings suggest that diet might alter the risk of developing MGUS and progression to MM.The AGES-Reykjavik Study was funded by NIH contract N01-AG-012100, the Intramural Research Program of the National Institute on Aging, by the Icelandic Heart Association, and the Icelandic Parliament. This work was supported by the Icelandic Centre for Research, RANNIS (S.Y. Kristinsson), the Landspitali University Hospital Research Fund (S.Y. Kristinsson), the Karolinska Instituted Foundations (S.Y. Kristinsson), the Marie Curie CIG (S.Y. Kristinsson), and the Memorial Sloan Kettering Core Grant (P30 CA008748) from the National Cancer Institute (O.Landgren). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer Reviewe

Molecular benchmarks of a SARS-CoV-2 epidemic.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadA pressing concern in the SARS-CoV-2 epidemic and other viral outbreaks, is the extent to which the containment measures are halting the viral spread. A straightforward way to assess this is to tally the active cases and the recovered ones throughout the epidemic. Here, we show how epidemic control can be assessed with molecular information during a well characterized epidemic in Iceland. We demonstrate how the viral concentration decreased in those newly diagnosed as the epidemic transitioned from exponential growth phase to containment phase. The viral concentration in the cases identified in population screening decreased faster than in those symptomatic and considered at high risk and that were targeted by the healthcare system. The viral concentration persists in recovering individuals as we found that half of the cases are still positive after two weeks. We demonstrate that accumulation of mutations in SARS-CoV-2 genome can be exploited to track the rate of new viral generations throughout the different phases of the epidemic, where the accumulation of mutations decreases as the transmission rate decreases in the containment phase. Overall, the molecular signatures of SARS-CoV-2 infections contain valuable epidemiological information that can be used to assess the effectiveness of containment measures

Dietary patterns in adolescence and risk of colorectal cancer: a population-based study.

To access publisher's full text version of this article click on the hyperlink belowPurpose: To study whether dietary patterns in adolescence are associated with risk of colorectal cancer (CRC). Methods: Food frequency data were obtained from the AGES-Reykjavik study, conducted between 2002 and 2006, which included 5,078 (58% women) participants with mean age of 77 (± 5.8) years. Principal component analysis was used to identify dietary patterns. Participants were followed through linkage to the Icelandic Cancer Registry. Multivariable Cox models were used to calculate hazard ratios (HR) of CRC and 95% confidence interval (CI) by dietary patterns. Results: During the follow-up period (mean 8.2 years), 136 participants (75 women and 61 men) were diagnosed with CRC. The main dietary pattern in adolescence was characterized by high intake of traditional food items consumed in the earlier half of the twentieth century, namely, salted or smoked meat and fish, milk, offal, rye bread, and oatmeal. Compared to the lowest tertile, the middle tertile of this pattern was associated with increased risk of CRC (HR 1.63, 95% CI 1.04-2.57), while the highest tertile was not statistically associated with CRC (HR 1.48, 95% CI 0.93-2.37), except among women (HR 2.06, 95% CI 1.11-3.84). Conclusion: These data suggest that strong adherence to a traditional Icelandic diet in adolescence might increase the risk of CRC, particularly among women. More research is need on the association between food items and dietary patterns of relevance to CRC at different points in the life cycle. Keywords: Adolescent; Colorectal cancer; Dietary pattern; Epidemiology; Factor analysis.United States Department of Health & Human Services National Institutes of Health (NIH) - USA Appeared in source as:NIH United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Aging (NIA) Appeared in source as:Intramural Research Program of the National Institute on Aging United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Eye Institute (NEI) Icelandic Heart Association Icelandic Parliament University of Iceland Research Fund United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Aging (NIA

Using a Brief Mental Imagery Competing Task to Reduce the Number of Intrusive Memories : Exploratory Case Series With Trauma-Exposed Women

Background: Novel interventions should be developed for people who have undergone psychological trauma. In a previous case study, we found that the number of intrusive memories of trauma could be reduced with a novel intervention. The intervention included a brief memory reminder, a visuospatial task and mental rotation, and targeted trauma memory hotspots one at a time in separate sessions. Objective: This case series (N=3) extended the first case study with 3 new cases to determine whether a similar pattern of beneficial results is observed. We explored whether the brief intervention would result in reduced numbers of intrusive memories and whether it would impact symptoms of posttraumatic stress, depression and anxiety, and general functioning. Acceptability of the intervention was also explored. Methods: A total of 3 women completed the study: 2 with posttraumatic stress disorder and other comorbidities and 1 with subthreshold posttraumatic stress disorder. The primary outcome was the change in the number of intrusive memories from the baseline phase to the intervention phase and at the 1-month follow-up, with an assessment of the intrusion frequency at 3 months. Participants monitored the number of intrusive memories in a daily diary for 1 week at baseline, for maximum of 6 weeks during the intervention phase and for 1 week at the 1-month and 3-month follow-ups. The intervention was delivered in person or digitally, with guidance from a clinical psychologist. A repeated AB design was used (A was a preintervention baseline phase and B intervention phase). Intrusions were targeted individually, creating repetitions of an AB design. Results: The total number of intrusive memories was reduced from the baseline to the intervention phase for all participants. The total number for participant 3 (P3) reduced from 38.8 per week during the baseline phase to 18.0 per week in the intervention phase. It was 13 at the 3-month follow-up. The total number for P4 reduced from 10.8 per week at baseline to 4.7 per week in the intervention phase. It was 0 at the 3-month follow-up. The total number for P5 was reduced from 33.7 at baseline to 20.7 per week in the intervention phase. It was 8 at the 3-month follow-up. All participants reported reduction in posttraumatic stress symptoms in the postintervention phase. Depression and anxiety symptoms reduced in 2 of the 3 participants in the postintervention phase. Acceptability was favorable. Conclusions: We observed good compliance with the intervention and intrusive memory diary in all 3 cases. The number of intrusive memories was reduced for all participants during the intervention phase and at the 1-month follow-up, with some improvement in other symptoms and functioning. Further research should explore the remote delivery of the intervention and whether nonspecialists can deliver the intervention effectively

Correction: Dietary habits in adolescence and midlife and risk of breast cancer in older women.

[This corrects the article DOI: 10.1371/journal.pone.0198017.]

Obesity and Risk of Monoclonal Gammopathy of Undetermined Significance: A Population-Based Study

Abstract Background Nearly all multiple myelomas (MM) are preceded by the premalignant state, monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic condition that needs no treatment. The etiology of MGUS and MM is to a large extent unknown. Two studies on the association between obesity and MGUS have been conducted with conflicting results, despite a reported association between obesity and MM. The aim of this study was to determine if obesity is associated with an increased risk of MGUS and light-chain MGUS (LC-MGUS) in a population-based screened cohort of individuals above the age of 65 years using extensive number of markers for current and early life obesity. Methods This study was based on participants from the Age, Gene/Environment Susceptibility – Reykjavik Study (AGES-RS), which is a continuation of the Reykjavik Study, a population-based study performed by the Icelandic Heart Association. In 1967, the Reykjavik Study began recruiting a sample of over 30,000 residents of Reykjavik from the 1907-1935 birth cohorts. In 2002, the AGES-RS began recruiting 5,764 of the surviving members. Serum protein electrophoresis (SPEP) and serum free light-chain assay were performed on all subjects. Obesity measures were performed at baseline, and participants were additionally asked about their weight at the age of 25 years. The measures at baseline included were weight (kg), body mass index (BMI) (kg/m2), percent body fat, fat (kg), and fat-free mass (kg) from bioimpedance, total body fat area (cm2), visceral and subcutaneous fat area (cm2), and waist circumference (cm). The association with MGUS and LC-MGUS was analyzed using logistic regression and adjustment was made for age and sex. Cox proportional-hazard regression was performed to test whether obesity was a risk factor for progression from MGUS to MM and lymphoproliferative diseases. Results A total of 304 (5.3%) MGUS cases and 118 participants (2.1%) with LC-MGUS were identified. No association was found between any of the obesity markers and MGUS (Table). A statistically significant positive association was found between obesity (BMI ≥ 30 kg/m2) at study baseline and LC-MGUS (Table). Weak but statistically significant association was found between LC-MGUS and BMI at baseline, weight, max weight, percent body fat, fat in kg, fat-free mass, and waist circumference (Table). No association was found on risk of MGUS using joint effect of early adulthood BMI and BMI at study entry. Analysis on the effect of the obesity markers on the progression from MGUS to MM and lymphoproliferative diseases showed no association. Conclusion In this large population-based cross-sectional study aimed at evaluating the association between obesity and MGUS and LC-MGUS, we found obesity (BMI ≥ 30 kg/m2) to be associated with 2-fold excess risk for LC-MGUS. An association was additionally found between several of the obesity markers used and LC-MGUS. Future studies are needed to clarify underlying mechanisms for this finding. However, we did not find an association between any of the obesity markers and MGUS. Taken together, we were unable to confirm the previously reported association between MGUS and obesity. Abstract 5706. Table: Obesity and risk of MGUS or light-chain MGUS (LC-MGUS) No MGUS MGUS LC-MGUS No MGUS vs. MGUS OR* (95%CI) No MGUS vs. LC MGUS OR* (95%CI) BMI (n) <25 1783 102 26 Reference Reference 25-30 2286 147 55 1.15 (0.88 - 1.50) 1.55 (0.97 - 2.49) ≥30 1176 51 34 0.85 (0.60 - 1.20) 2.12 (1.26 - 3.58) BMI 25y (n) <25 3949 220 83 Reference Reference ≥25 809 44 25 0.87 (0.62-1.22) 1.13 (0.71-1.79) BMI (kg/m2) 27.0 26.7 28.3 1.00 (0.97 - 1.02) 1.07 (1.03 - 1.12) BMI 25y (kg/m2) 22.8 22.9 22.9 0.99 (0.94 - 1.04) 0.93 (0.86 - 1.01) Weight (kg) 75.2 75.3 84.1 1.00 (0.99 - 1.01) 1.03 (1.02 - 1.04) Max weight (kg) 80.6 82.3 89.1 1.00 (0.99 - 1.01) 1.02 (1.01 - 1.03) Percent body fat (%) 28.9 26.8 27.2 0.99 (0.97 - 1.02) 1.04 (1.01 - 1.07) Fat (kg) 21.9 20.5 22.7 1.00 (0.98 - 1.02) 1.04 (1.01 - 1.07) Fat free mass (kg) 53.4 55.4 60.3 1.00 (0.98 - 1.02) 1.04 (1.01 - 1.07) Total body fat area (cm2) 493.1 481.8 543.2 1.00 (1.00 - 1.00) 1.00 (1.00 - 1.00) Visceral fat area (cm2) 171.8 174.4 209.4 1.00 (1.00 - 1.00) 1.00 (1.00 - 1.00) Subcutaneous fat area (cm2) 256.3 241.6 260.1 1.00 (1.00 - 1.00) 1.00 (1.00 - 1.00) CT waist circumference (cm) 125.7 125.7 131.1 1.00 (0.99 - 1.01) 1.03 (1.01 - 1.04) Waist circumference (cm) 100.7 100.8 105.6 1.00 (0.99 - 1.01) 1.03 (1.01 - 1.05) *Adjusted for age and sex Disclosures No relevant conflicts of interest to declare

Dietary Pattern and Risk of Monoclonal Gammopathy of Undetermined Significance: A Population-Based Study

Abstract Background: All multiple myeloma (MM) cases are preceded by the premalignant state, monoclonal gammopathy of undetermined significance (MGUS). The etiology of MM and MGUS is to a large extent unknown. Few studies on the effect of diet on MM have been conducted and the results have been inconclusive. No studies have been conducted on the effect of diet on MGUS. Studying dietary patterns offers broader view of food consumption and possible effects of diet on diseases since many nutrients and other substances in foods act together. The aim of this study was to identify different dietary patterns at three time points throughout the lifespan and examine whether adherence to these patterns was associated with risk of MGUS and light chain MGUS (LC-MGUS) and progression to MM and other lymphoproliferative diseases. Methods: This study was based on participants from the AGES-Reykjavik Study (N=5,764; mean age 77 years). Participants gave information on frequency of intake of common foods from early life (14-19 years old), midlife (45-55 years old), and currently at study baseline (67 years and older). All participants were screened for MGUS and LC-MGUS by serum protein electrophoresis and serum free light-chain assay. We identified MM and other lymphoproliferative diseases by cross linking with the Icelandic Cancer Registry. Principal component analysis was used to extract dietary patterns. This method is data driven and forms new linear factors, (dietary patterns) by reducing data dimension and grouping correlated variables (food intake). For each pattern extracted a new variable is created, ranking participants on their adherence to that particular pattern. We used logistic regression to test association between adherence to the early life and midlife dietary patterns and MGUS and LC-MGUS, and Cox proportional hazard regression to test association between adherence to the late life patterns and progression to MM and other lymphoproliferative diseases. Results: A total of 300 (5.2%) MGUS cases and 52 (0.9%) LC-MGUS cases were identified. During 11 years of follow-up 18 cases had progressed to MM and 10 to other lymphoproliferative diseases. We extracted four dietary patterns from early life, four from midlife, and six from baseline. When analyzing MGUS and LC-MGUS cases combined we found that high adherence to pattern I from early life, the old traditional Icelandic diet (high intake of salted/smoked meat and fish, blood and liver sausage, rye bread, milk, oatmeal, and potatoes), decreased the risk (odds ratio (OR) = 0.89, 95% confidence interval (CI) 0.79-1.00), however no association was found when analyzing MGUS and LC-MGUS separately (Table 1). When analyzing midlife patterns we found that the estimate for pattern I, the old traditional Icelandic diet (high intake of salted/smoked meat and fish, blood and liver sausage, fish in salad or on bread, and meat meals) was similar to the findings from early life, although it did not reach a statistical significance (OR = 0.90, 95% CI 0.80 - 1.02). High adherence to pattern III (high intake of potatoes, whole wheat bread, milk, rye bread, and fish) from midlife decreased the risk of combined MGUS (OR = 0.88, 95% CI 0.79-0.98). When analyzing MGUS and LC-MGUS separately we found that high adherence to pattern III decreased the risk of LC-MGUS (OR = 0.69, 95% CI 0.53-0.90) but not MGUS. We did not find an association between the six patterns from late life and progression to MM. However when analyzing progression to MM and other lymphoproliferative diseases combined we found that high adherence to pattern VI (high intake of meat and milk, low intake of fish) increased the risk of progression (HR = 1.82, 95% CI 1.24-2.67). Further results can be seen in Table 1. Conclusion: Our findings suggest that high adherence to the old traditional Icelandic diet consumed during early and mid 19th century, including salted or smoked meat and fish, blood or liver sausage, rye bread, and potatoes decreases the risk of MGUS/LC-MGUS later in life. They additionally suggest an increased risk of progression to MM and other lymphoproliferative diseases, with high adherence to a pattern with high meat and low fish intake. The mechanisms for these findings are unknown but our study suggests that food intake can alter the risk of developing MGUS/LC-MGUS as well as the risk of progression to MM. Disclosures Korde: Medscape: Honoraria. Landgren:Medscape Myeloma Program: Honoraria; BMS: Honoraria; Takeda: Honoraria; Merck: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding