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Background: Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Use of electronic health records may facilitate large-scale epidemiologic research to elucidate risk factors for the progression of MGUS to MM or other lymphoid malignancies., Aims: We evaluated the accuracy of an electronic health records-based approach for identifying clinically diagnosed MGUS cases for inclusion in studies of patient outcomes/ progression risk., Methods and Results: Data were retrieved from Kaiser Permanente Southern California's comprehensive electronic health records, which contain documentation of all outpatient and inpatient visits, laboratory tests, diagnosis codes and a cancer registry. We ascertained potential MGUS cases diagnosed between 2008 and 2014 using the presence of an MGUS ICD-9 diagnosis code (273.1). We initially excluded those diagnosed with MM within 6 months after MGUS diagnosis, then subsequently those with any lymphoid malignancy diagnosis from 2007 to 2014. We reviewed medical charts for 100 randomly selected potential cases for evidence of a physician diagnosis of MGUS, which served as our gold standard for case confirmation. To assess sensitivity, we also investigated the presence of the ICD-9 code in the records of 40 randomly selected and chart review-confirmed MGUS cases among patients with a laboratory report of elevated circulating monoclonal (M-) protein (a key test for MGUS diagnosis) and no subsequent lymphoid malignancy (as described above). The positive predictive value (PPV) for the ICD-9 code was 98%. All MGUS cases confirmed by chart review also had confirmatory laboratory test results. Of the confirmed cases first identified via M-protein test results, 88% also had the ICD-9 diagnosis code., Conclusion: The diagnosis code-based approach has excellent PPV and likely high sensitivity for detecting clinically diagnosed MGUS. The generalizability of this approach outside an integrated healthcare system warrants further evaluation., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: 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 well studied., Methods: 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., Results: Each 5 kg/m 2 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/m 2 : 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)., Conclusions: These findings highlight the importance of avoidance of overweight/obesity and excess adiposity throughout adulthood as a potential MM risk-reduction strategy., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Cadmium and lead are persistent environmental toxins that are known or probable carcinogens, based on evidence for causality for nonhematologic cancers. Associations of these metals with risk of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are unknown but biologically plausible. To examine the associations of circulating levels of lead and cadmium exposure with risk of B-cell NHL (B-NHL) and multiple myeloma, we conducted a nested case-control study among 299 incident B-cell NHLs and 76 MM cases within the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC). Each case was incidence-density matched to two eligible controls on age, race, sex and blood draw date. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) for lymphoid malignancies overall and stratified by subtype. We observed a significant positive association between high erythrocyte lead concentration and risk of lymphoid malignancies overall (RR = 1.16, 95% CI: 1.02-1.33 per 17.6 μg/L (1 standard deviation [SD])) and follicular lymphoma in particular (RR = 1.80, 95% CI: 1.15-2.80 per SD). In contrast, there was no association between erythrocyte cadmium and risk of B-NHL (RR = 0.89, 95% CI: 0.75-1.06 per 0.37 μg/L [1 SD]), or any B-NHL subtypes; but a strong inverse association with MM risk (RR = 0.59, 95% CI: 0.38-0.89, per SD). Results from our study suggest a positive association between erythrocyte lead level and risk of lymphoid malignancies and a possible inverse association between cadmium and myeloma. Additional research is needed to confirm and further explore these findings., (© 2020 UICC.)

Background: Resistin is a polypeptide hormone secreted by adipose tissue. A prior hospital-based case-control study reported serum resistin levels to be inversely associated with risk of multiple myeloma (MM). To date, this association has not been investigated prospectively., Methods: We measured resistin concentrations for pre-diagnosis peripheral blood samples from 178 MM cases and 358 individually matched controls from three cohorts participating in the MM cohort consortium., Results: In overall analyses, higher resistin levels were weakly associated with reduced MM risk. For men, we observed a statistically significant inverse association between resistin levels and MM (odds ratio, 0.44; 95% confidence interval (CI) 0.24-0.83 and 0.54; 95% CI 0.29-0.99, for the third and fourth quartiles, respectively, vs the lowest quartile; P trend =0.03). No association was observed for women., Conclusions: This study provides the first prospective evidence that low circulating resistin levels may be associated with an increased risk of MM, particularly for men.

Multiple myeloma (MM) incidence and mortality are higher among African Americans (AAs) than among other population groups. The prevalence of obesity is also elevated among AAs, but few studies have examined risk of this cancer in relation to body size among AAs. We combined data from seven prospective cohorts tracking mortality among 239 597 AA adults and used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for death because of MM according to body mass index (BMI) at cohort entry, adjusted for age (as time-scale) and sex. Relative to those with normal BMIs (18.5-25 kg/m(2)), mortality increased monotonically as BMI increased, with hazard ratios reaching 1.43 (95% CI = 1.03 to 1.97) for BMIs of 35 kg/m(2) or greater. The findings suggest that obesity is a risk factor for MM and a contributor to the elevated rates and rising incidence trends of MM among AAs in the United States., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The association between obesity and multiple myeloma risk may be partly attributed to reduced circulating levels of adiponectin in obese individuals. To prospectively evaluate multiple myeloma risk in relation to adiponectin levels overall and stratified by body mass index and other characteristics, we conducted a pooled investigation of pre-diagnosed peripheral blood samples from 624 multiple myeloma cases and 1,246 individually matched controls from seven cohorts participating in the Multiple Myeloma Cohort Consortium. Analysis of circulating analyte levels measured by ELISA revealed that higher total adiponectin levels were associated with reduced multiple myeloma risk overall [highest quartile vs. lowest: OR, 0.64; 95% confidence interval (CI) 0.47-0.85; Ptrend = 0.001]. This association was apparent among cases diagnosed six or more years after blood collection (OR, 0.60; 95% CI, 0.40-0.90; Ptrend = 0.004) and was similar in magnitude for men and women (OR, 0.59 and 0.66, respectively). Interestingly, we observed strong associations among subjects who were overweight (OR, 0.41; 95% CI, 0.26-0.65) or obese (OR, 0.41; 95% CI, 0.17-0.98) but not among those with normal weight (OR, 1.20; 95% CI, 0.73-2.00; overweight/obese vs. normal weight, Pinteraction = 0.04). Our findings provide the strongest epidemiologic evidence to date that adiponectin protects against multiple myeloma development, particularly among overweight and obese individuals, and offer a method for risk assessment in this susceptible population of heavier patients. Cancer Res; 76(7); 1935-41. ©2016 AACR., (©2016 American Association for Cancer Research.)

Multiple myeloma (MM) is a rare but highly fatal malignancy. High body weight is associated with this cancer, but several questions remain regarding the aetiological relevance of timing and location of body weight. To address these questions, we conducted a pooled analysis of MM mortality using 1·5 million participants (including 1388 MM deaths) from 20 prospective cohorts in the National Cancer Institute Cohort Consortium. Proportional hazards regression was used to calculate pooled multivariate hazard ratios (HRs) and 95% confidence intervals (CIs). Associations with elevated MM mortality were observed for higher early-adult body mass index (BMI; HR = 1·22, 95% CI: 1·09-1·35 per 5 kg/m(2) ) and for higher cohort-entry BMI (HR 1·09, 95% CI: 1·03-1·16 per 5 kg/m(2) ) and waist circumference (HR = 1·06, 95% CI: 1·02-1·10 per 5 cm). Women who were the heaviest, both in early adulthood (BMI 25+) and at cohort entry (BMI 30+) were at greater risk compared to those with BMI 18·5 ≤ 25 at both time points (HR = 1·95, 95% CI: 1·33-2·86). Waist-to-hip ratio and height were not associated with MM mortality. These observations suggest that overall, and possibly also central, obesity influence myeloma mortality, and women have the highest risk of death from this cancer if they remain heavy throughout adulthood., (© 2014 John Wiley & Sons Ltd.)