A Prospective Study of Circulating Adipokine Levels and Risk of Multiple Myeloma

Abstract

Abstract Purpose: Obesity is associated with an increased risk of multiple myeloma (MM), although the biologic mechanisms underlying this association are unclear. We conducted a nested case-control study in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial to evaluate the hypothesis that altered circulating levels of adipokines, polypeptide hormones with pro- and anti-inflammatory properties secreted by adipose tissue, may partly explain the association between obesity and MM. Methods: We investigated whether circulating levels of leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin are associated with MM among 174 cases and 348 controls in PLCO. Two controls were matched to each case on age at baseline, sex, race, date of phlebotomy, time of day of phlebotomy, and study year of specimen collection. Plasma adipokine concentrations were measured by enzyme-linked immunosorbent assay; overall coefficients of variation were ≤8.5%. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: Inverse associations with MM were observed for total adiponectin (highest quartile vs. lowest: OR = 0.49, 95% CI = 0.26–0.93, P-trend = 0.03) and HMW adiponectin (OR = 0.44, 95% CI = 0.23–0.85, P-trend = 0.01). These associations remained after adjusting for body mass index (BMI), stratifying by sex, and restricting to cases diagnosed approximately eight years or more after blood collection. We observed a modest association between BMI and MM (OR per 5 kg/m2 increase = 1.14, 95% CI = 0.94–1.39), which was attenuated by approximately 40% after adjusting for adiponectin. Leptin levels were not associated with MM. Conclusions: These results suggest that higher circulating levels of adiponectin are protective against MM, and that adiponectin may play an important role in obesity-related myelomagenesis. This study is, to our knowledge, the first prospective investigation of circulating adipokines and MM. Our findings are particularly intriguing in light of recent evidence that host-derived adiponectin is tumor-suppressive and a potential novel therapeutic target for MM and associated bone disease.