Abstract
Abstract
Background: Excess body weight throughout adult life has been consistently associated with an increased risk of multiple myeloma (MM). This association may be due in part to reduced expression of adiponectin, as circulating levels of this anti-inflammatory hormone are typically lower in obese individuals compared with those of normal body weight. Studies conducted in vitro and in animal models have found that adiponectin induces myeloma cell apoptosis. Furthermore, in a recent prospective study in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, we observed a lower risk of MM among those with higher pre-diagnosis circulating levels of adiponectin. To follow up on our findings from PLCO and increase our statistical power for analyses stratified by sex, follow-up time, and other factors, we conducted a pooled investigation of circulating adiponectin levels and MM risk using the NCI Cohort Consortium.
Methods: Our study included pre-diagnosis peripheral blood samples from 450 MM cases and 898 individually-matched controls from the following 6 cohorts: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study; the Cancer Prevention Study II; the Health Professionals Follow-up Study; the Melbourne Collaborative Cohort Study; the Nurses’ Health Study; and the Women's Health Initiative. We performed additional analyses incorporating data from our original investigation in PLCO for a total of 624 MM cases and 1,246 controls. Circulating levels of total adiponectin were measured in duplicate using standard enzyme-linked immunosorbent assay (ELISA) methods. We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for risk of MM in relation to quartiles of cohort- and sex-adjusted adiponectin levels based on the distribution among controls.
Results: Higher circulating levels of adiponectin were associated with a reduced risk of MM in the independent replication set (highest quartile vs. lowest: OR 0.68, 95% CI 0.48-0.96; P-trend = 0.02) and in the combined set including PLCO (OR 0.64, 95% CI 0.47-0.85; P-trend = 0.001). This association was also present in analyses restricted to cases diagnosed 6 or more years after blood collection (OR 0.60, 95% CI 0.40-0.90; P-trend = 0.004). The observed associations were similar in magnitude for men and women (ORs of 0.59 and 0.66, respectively), and results were unchanged after adjustment for body mass index.
Conclusions: The findings of this pooled investigation provide the strongest epidemiologic evidence to date that adiponectin may protect against development of MM. Further research is needed to characterize the role of this metabolic hormone in progression from the MM precursor monoclonal gammopathy of undetermined significance to clinically manifest disease, and to evaluate the clinical implications of our findings for risk reduction and therapy for MM and associated bone disease.
Citation Format: Jonathan N. Hofmann, Brenda M. Birmann, Lauren R. Teras, Ye Wang, Demetrius Albanes, Dalsu Baris, Graham A. Colditz, Anneclaire J. De Roos, Graham G. Giles, Lindsay M. Morton, H. Dean Hosgood, Qing Lan, Ola Landgren, Linda M. Liao, Ruth M. Pfeiffer, Nathaniel Rothman, Stephanie J. Weinstein, Michael N. Pollak, Marian L. Neuhouser, Mark P. Purdue. A pooled investigation of circulating adiponectin levels and risk of multiple myeloma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 934. doi:10.1158/1538-7445.AM2015-934
