Pre-diagnostic biomarkers of metabolic dysregulation and cancer mortality

Tomi Akinyemiju, Justin Xavier Moore, Suzanne E. Judd, Maria Pisu, Michael Goodman, Virginia J. Howard, Leann Long, Monika Safford, Susan C. Gilchrist, Mary Cushman

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)16099-16109
Number of pages11
JournalOncotarget
Volume9
Issue number22
DOIs
StatePublished - Jan 1 2018

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Biomarkers
Resistin
Mortality
Neoplasms
Leptin
Confidence Intervals
Adiponectin
Lipoprotein(a)
Proportional Hazards Models
Comorbidity
Obesity
Smoking
Stroke
Alcohols
Hormones
Exercise
Neoplasm Metastasis
Inflammation
Education
Serum

Keywords

  • Cancer mortality
  • Metabolic biomarkers
  • Metabolism
  • Racial disparities

ASJC Scopus subject areas

  • Oncology

Cite this

Akinyemiju, T., Moore, J. X., Judd, S. E., Pisu, M., Goodman, M., Howard, V. J., ... Cushman, M. (2018). Pre-diagnostic biomarkers of metabolic dysregulation and cancer mortality. Oncotarget, 9(22), 16099-16109. https://doi.org/10.18632/oncotarget.24559

Pre-diagnostic biomarkers of metabolic dysregulation and cancer mortality. / Akinyemiju, Tomi; Moore, Justin Xavier; Judd, Suzanne E.; Pisu, Maria; Goodman, Michael; Howard, Virginia J.; Long, Leann; Safford, Monika; Gilchrist, Susan C.; Cushman, Mary.

In: Oncotarget, Vol. 9, No. 22, 01.01.2018, p. 16099-16109.

Research output: Contribution to journalArticle

Akinyemiju, T, Moore, JX, Judd, SE, Pisu, M, Goodman, M, Howard, VJ, Long, L, Safford, M, Gilchrist, SC & Cushman, M 2018, 'Pre-diagnostic biomarkers of metabolic dysregulation and cancer mortality', Oncotarget, vol. 9, no. 22, pp. 16099-16109. https://doi.org/10.18632/oncotarget.24559
Akinyemiju T, Moore JX, Judd SE, Pisu M, Goodman M, Howard VJ et al. Pre-diagnostic biomarkers of metabolic dysregulation and cancer mortality. Oncotarget. 2018 Jan 1;9(22):16099-16109. https://doi.org/10.18632/oncotarget.24559
Akinyemiju, Tomi ; Moore, Justin Xavier ; Judd, Suzanne E. ; Pisu, Maria ; Goodman, Michael ; Howard, Virginia J. ; Long, Leann ; Safford, Monika ; Gilchrist, Susan C. ; Cushman, Mary. / Pre-diagnostic biomarkers of metabolic dysregulation and cancer mortality. In: Oncotarget. 2018 ; Vol. 9, No. 22. pp. 16099-16109.
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N2 - 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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