INTRODUCTION: The obesogenic milieu is a pro-tumorigenic environment that promotes tumor initiation, angiogenesis and metastasis. In this prospective cohort, we examined the association between pre-diagnostic metabolic biomarkers, plasma adiponectin, resistin, leptin and lipoprotein (a), and the risk of cancer mortality.

METHODS: Prospective data was obtained from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of Blacks and Whites followed from 2003 through 2012 for cancer mortality. We determined the association between metabolism biomarkers (log-transformed and tertiles) and risk of cancer mortality using Cox Proportional Hazards models with robust sandwich estimators to calculate the 95% confidence intervals (CIs), and adjusted for baseline covariates, including age, gender, income, education, physical activity, BMI, smoking status, alcohol use, and comorbidity score.

RESULTS: Among 1764 participants with available biomarker data, each SD higher log-leptin was associated with a 54% reduced risk of total cancer mortality (HR: 0.46, 95% CI: 0.23 - 0.92) and obesity-related cancer mortality (HR: 0.55, 95% CI: 0.39-0.79). Among Blacks only, each SD higher log-resistin was associated with a nearly 7-fold increased risk of cancer mortality (adjusted HR: 6.68, 95% CI: 2.10 - 21.21). There were no significant associations of adiponectin or Lp(a) and cancer mortality.

CONCLUSIONS: Leptin is involved in long-term regulation of energy balance, while resistin is involved in chronic inflammation and LDL production. These findings highlight the biological mechanisms linking metabolic dysregulation with cancer mortality, and the influence of resistin on cancer mortality only among Blacks suggests that this hormone may be a useful biomarker of racial differences in cancer mortality that deserves further study.

IMPACT: Our observed increased risk of cancer mortality associated with higher serum resistin levels among Blacks suggests that if validated in larger cohorts, clinical strategies focused on resistin control may be a promising cancer prevention strategy.

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Published in Oncotarget, v. 9, no. 22, p. 16099-16109.

Copyright: Akinyemiju et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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The REGARDS study was supported by cooperative agreement U01-NS041588 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Service. This analysis was supported by award R01-NR012726 from the National Institute for Nursing Research, UL1-RR025777 from the National Center for Research Resources, K08HL096841 and R01HL080477 from the National Heart, Lung, and Blood Institute, as well as by grants from the Center for Clinical and Translational Science and the Lister Hill Center for Health Policy of the University of Alabama at Birmingham. Dr. Akinyemiju was supported by grants U54 CA118948 and K01 TW010271-01A1 from the NIH. Dr. Moore was supported by grants R25 CA47888 and T32190194 from the National Cancer Institute, by the foundation for Barnes Jewish Hospital, and by the Siteman Cancer Center.

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