Body Mass Index and Physical Activity at Different Ages and Risk of Multiple Myeloma in the NIH-AARP Diet and Health Study
Several studies have reported an increased risk of multiple myeloma associated with excess body weight. We investigated the risk of multiple myeloma in relation to separate measures of adiposity and energy balance at different ages in the National Institutes of Health-AARP Diet and Health Study, a large prospective cohort study in the United States. Participants completed a baseline questionnaire (1995-1996; n = 485,049), and a subset of participants completed a second questionnaire (1996-1997; n = 305,618) in which we solicited more detailed exposure information. Hazard ratios and 95% confidence intervals were estimated for the risk of multiple myeloma (overall, n = 813; subset, n = 489) in relation to several measures of obesity and leisure time physical activity. Multiple myeloma risk was associated with increasing body mass index (BMI) at cohort entry (per 5-kg/m(2) increase, hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.00, 1.22); similar associations were observed for BMI at age 50 years (HR = 1.14, 95% CI: 1.02, 1.28), age 35 years (HR = 1.20, 95% CI: 1.05, 1.36), and age 18 years (HR = 1.13, 95% CI: 0.98, 1.32) without adjustment for baseline BMI. Risk of multiple myeloma was not associated with physical activity level at any age. These findings support the hypothesis that excess body weight, both in early adulthood and later in life, is a risk factor for multiple myeloma and suggest that maintaining a healthy body weight throughout life may reduce multiple myeloma risk.
Available from: Sai-Ching Yeung
- "These signalling pathways are also activated by insulin and insulin-like growth factors in obesity and insulin-resistant conditions , including type 2 diabetes mellitus (Reseland et al, 2009). Although obesity (Wallin and Larsson, 2011; Hofmann et al, 2013) and diabetes (Boffetta et al, 1989; Fortuny et al, 2005) are associated with an increased MM incidence, the impact of diabetes on the clinical outcome of MM after diagnosis (i.e., prognosis) has only been investigated in a Taiwanese study (Chou et al, 2012), which found that pre-existing diabetes was associated with advanced stage and poor overall survival (OS). The potential impacts of steroid-induced diabetes (SID) and anti-diabetic medications on MM have not been reviewed in clinical cohorts. "
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Insulin/insulin-like growth factor-1 signalling may underlie the promoting effect of type 2 diabetes on cancer. This study examined the association of diabetes, including steroid-induced diabetes (SID), and the impact of anti-diabetic medication on clinical outcomes of multiple myeloma (MM).
A retrospective review was conducted of 1240 MM patients. Overall survival (OS) and MM disease status prior to death were analysed.
Diabetic patients had a significantly shorter OS than non-diabetic patients (median: 65.4 vs 98.7 months). In multivariate analysis, SID was a significant predictor of decreased OS, along with age, comorbidity, MM stage, and cytogenetic abnormalities. Analyzing only the diabetic MM patients, Cox regression showed that metformin predicted an increased OS, whereas use of insulin/analogues predicted a decreased OS. Competing risk analysis showed that DM was associated with increased cumulative incidence of death with progressive MM. Among the diabetics, multivariate regression showed that insulin/analogues were associated with increased, but metformin with decreased death with progressive MM. Potential immortal time bias was evaluated by landmark analyses.
DM, SID in particular, is associated with poor clinical outcomes in MM. Insulin/analogues are associated with poor outcomes, whereas metformin is associated with improved outcomes. No conclusion about causal relationships can be made at this time. Managing hyperglycaemia with non-insulin regimens should be investigated in randomised trials.
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ABSTRACT: Background: Despite the existence of numerous biologic pathways potentially linking increased physical activity to decreased risk of hematologic cancers, the associations between physical activity and subtype-specific hematologic cancers have not been comprehensively quantified. Methods: We conducted a systematic review and meta-analysis of physical activity in relation to subtype-specific hematologic cancers. We summarized the data from 23 eligible studies (15 cohort and 8 case-control studies) and estimated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects models. Results: When comparing high versus low physical activity levels, the RR for non-Hodgkin lymphoma was 0.91 (95% CI=0.82-1.00), for Hodgkin lymphoma it was 0.86 (95% CI=0.58-1.26), for leukemia it was 0.97 (95% CI=0.84-1.13), and for multiple myeloma it was 0.86 (95% CI=0.68-1.09). When focusing on subtypes of non-Hodgkin lymphoma, the RR for diffuse large B-cell lymphoma was 0.95 (95% CI=0.80-1.14) and for follicular lymphoma it was 1.01 (95% CI=0.83-1.22). In an exploratory analysis combining all hematologic cancers, high versus low physical activity levels yielded a statistically significant RR of 0.93 (95% CI=0.88-0.99) Conclusions: Physical activity showed statistically non-significant associations with risks of non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, and leukemia. These findings may not represent a true lack of associations given the variation in high versus low physical activity definitions, the quality of physical activity assessments, and the variability in hematologic cancer classification schemes in individual studies. Impact: Physical activity is unrelated to risks of subtype-specific hematologic cancers.
Available from: Cari M Kitahara
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ABSTRACT: 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.
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