Manol Jovani1,2,3,4, Elizabeth E Liu5, Samantha M Paniagua5, Emily S Lau6,7,8, Shawn X Li8, Katherine S Takvorian8, Bernard E Kreger9,10, Greta Lee Splansky10, Rudolf A de Boer11, Amit D Joshi1,2,3, Shih Jen Hwang10,12, Chen Yao10,12, Tianxiao Huan10,12, Paul Courchesne10,12, Martin G Larson10,13, Daniel Levy10,12, Andrew T Chan1,2,3, Jennifer E Ho2,3,5,6,7,8. 1. Division of Gastroenterology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. 2. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. 3. Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA. 4. Division of Gastroenterology, University of Kentucky Albert B. Chandler Hospital, 800 Rose Street, Lexington, KY 40536, USA. 5. Cardiovascular Research Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. 6. Corrigan Minehan Heart Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. 7. Cardiology Division, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. 8. Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. 9. General Internal Medicine, Department of Medicine, Boston University School of Medicine, 72 E Concord Street, Boston, MA 02118, USA. 10. The Framingham Heart Study, 73 Mt Wayte Avenue, Framingham, MA 01702, USA. 11. Department of Cardiology, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. 12. Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. 13. Department of Biostatistics, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA.
Abstract
AIMS: Recent studies suggest an association between cardiovascular disease (CVD) and cancer incidence/mortality, but the pathophysiological mechanisms underlying these associations are unclear. We aimed to examine biomarkers previously associated with CVD and study their association with incident cancer and cancer-related death in a prospective cohort study. METHODS AND RESULTS: We used a proteomic platform to measure 71 cardiovascular biomarkers among 5032 participants in the Framingham Heart Study who were free of cancer at baseline. We used multivariable-adjusted Cox models to examine the association of circulating protein biomarkers with risk of cancer incidence and mortality. To account for multiple testing, we set a 2-sided false discovery rate <0.05. Growth differentiation factor-15 (also known as macrophage inhibitory cytokine-1) was associated with increased risk of incident cancer [hazards ratio (HR) per 1 standard deviation increment 1.31, 95% CI 1.17-1.47], incident gastrointestinal cancer (HR 1.85, 95% CI 1.37-2.50), incident colorectal cancer (HR 1.94, 95% CI 1.29-2.91), and cancer-related death (HR 2.15, 95% CI 1.72-2.70). Stromal cell-derived factor-1 showed an inverse association with cancer-related death (HR 0.75, 95% CI 0.65-0.86). Fibroblast growth factor-23 showed an association with colorectal cancer (HR 1.55, 95% CI 1.20-2.00), and granulin was associated with haematologic cancer (HR 1.61, 95% CI 1.30-1.99). Other circulating biomarkers of inflammation, immune activation, metabolism, and fibrosis showed suggestive associations with future cancer diagnosis. CONCLUSION: We observed several significant associations between circulating CVD biomarkers and cancer, supporting the idea that shared biological pathways underlie both diseases. Further investigations of specific mechanisms that lead to both CVD and cancer are warranted. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Recent studies suggest an association between cardiovascular disease (CVD) and cancer incidence/mortality, but the pathophysiological mechanisms underlying these associations are unclear. We aimed to examine biomarkers previously associated with CVD and study their association with incident cancer and cancer-related death in a prospective cohort study. METHODS AND RESULTS: We used a proteomic platform to measure 71 cardiovascular biomarkers among 5032 participants in the Framingham Heart Study who were free of cancer at baseline. We used multivariable-adjusted Cox models to examine the association of circulating protein biomarkers with risk of cancer incidence and mortality. To account for multiple testing, we set a 2-sided false discovery rate <0.05. Growth differentiation factor-15 (also known as macrophage inhibitory cytokine-1) was associated with increased risk of incident cancer [hazards ratio (HR) per 1 standard deviation increment 1.31, 95% CI 1.17-1.47], incident gastrointestinal cancer (HR 1.85, 95% CI 1.37-2.50), incident colorectal cancer (HR 1.94, 95% CI 1.29-2.91), and cancer-related death (HR 2.15, 95% CI 1.72-2.70). Stromal cell-derived factor-1 showed an inverse association with cancer-related death (HR 0.75, 95% CI 0.65-0.86). Fibroblast growth factor-23 showed an association with colorectal cancer (HR 1.55, 95% CI 1.20-2.00), and granulin was associated with haematologic cancer (HR 1.61, 95% CI 1.30-1.99). Other circulating biomarkers of inflammation, immune activation, metabolism, and fibrosis showed suggestive associations with future cancer diagnosis. CONCLUSION: We observed several significant associations between circulating CVD biomarkers and cancer, supporting the idea that shared biological pathways underlie both diseases. Further investigations of specific mechanisms that lead to both CVD and cancer are warranted. Published on behalf of the European Society of Cardiology. All rights reserved.
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