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Investigator Names and Contact Information
Jonathan Hofmann [email@example.com ]
It has been hypothesized that the observed excess risk of multiple myeloma (MM) among obese individuals could be due to altered circulating levels of adiponectin, a polypeptide hormone with anti-inflammatory properties secreted by adipose tissue. In a recent prospective investigation of 174 MM cases and 348 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we observed inverse associations with MM for total adiponectin [highest quartile vs. lowest: odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.26-0.93, Ptrend = 0.03) and high-molecular-weight (HMW) adiponectin (OR = 0.44, 95% CI = 0.23-0.85, Ptrend = 0.01). These associations remained after restricting to MM cases diagnosed approximately eight years or more after blood collection. The results of this study, to our knowledge the first prospective investigation of circulating adipokines and MM, suggest that adiponectin may play a role in obesity-related myelomagenesis. Replication of these findings in other prospective cohorts is critical. We propose to conduct a pooled nested case-control study of MM risk in relation to total and HMW adiponectin using prospectively collected blood samples from other cohorts participating in the Multiple Myeloma Cohort Consortium. Measurements of circulating levels of total and HMW adiponectin will be performed in duplicate in the laboratory of Dr. Michael Pollak (Jewish General Hospital, Montreal, Canada); this assay requires 60 µL of serum or plasma per subject. We anticipate that approximately 200 MM cases and 400 matched controls (2:1 control-to-case ratio) will be selected from among participants in the Women's Health Initiative Clinical Trial (WHI-CT) and Observational Study (WHI-OS). With a combined total of approximately 500 cases and 1,000 controls across all participating cohorts, this study will have sufficient statistical power (≥80%) to detect a dose-response trend in MM risk if the OR comparing the highest and lowest quartiles is ≤0.66 (two-sided test, α=0.05).
Recent findings from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial suggest that circulating levels of adiponectin are inversely associated with risk of multiple myeloma. To follow up on these findings, we propose to conduct a pooled replication effort that includes participants in the Women's Health Initiative (WHI). Specifically, we will:
1. Evaluate risk of multiple myeloma in relation to total adiponectin, high-molecular-weight (HMW) adiponectin, and the ratio of HMW to total adiponectin;
2. Explore whether these associations differ by sex, race, age, body mass index (BMI), and with time from blood collection to case diagnosis; and
3. Explore through mediation analyses whether adjustment for adiponectin attenuates the association between BMI and multiple myeloma.
AS389 used the same cases and controls as AS207 [see AS207 Participant Selection Summary]