Cancer Causes & Control

, Volume 28, Issue 2, pp 127–136 | Cite as

Metabolic syndrome and total cancer mortality in the Third National Health and Nutrition Examination Survey

  • Wambui G. Gathirua-Mwangi
  • Patrick O. Monahan
  • Mwangi J. Murage
  • Jianjun Zhang
Original paper



Although metabolic syndrome incidence has substantially increased during the last few decades, it largely remains unclear whether this metabolic disorder is associated with total cancer mortality. The present study was carried out to investigate this important question.


A total of 687 cancer deaths were identified from 14,916 participants in the third National Health and Nutrition Examination Survey by linking them to the National Death Index database through December 31, 2006. Cox proportional hazards regression was performed to calculate hazard ratios (HR) and 95% confidence intervals (CI) for total cancer mortality in relation to metabolic syndrome and its individual components.


After adjustment for confounders, a diagnosis of metabolic syndrome was associated with 33% elevated total cancer mortality. Compared with individuals without metabolic syndrome, those with 3, 4 and 5 abnormal components had HRs (95% CIs) of 1.28 (1.03–1.59), 1.24 (0.96–1.60), and 1.87 (1.34–2.63), respectively (p-trend = 0.0003). Systolic blood pressure and serum glucose were associated with an increased risk of death from total cancer [HR (95% CI) for highest vs. lowest quartiles: 1.67 (1.19–2.33), p-trend = 0.002 and 1.34 (1.04–1.74), p-trend = 0.003, respectively]. Overall null results were obtained for lung cancer mortality. The effects of metabolic syndrome and its components on non-lung cancer mortality were generally similar to, but somewhat larger than, those for total cancer mortality.


Our study is among the first to reveal that metabolic syndrome is associated with increased total cancer mortality.


Metabolic syndrome Obesity Total cancer mortality Lung cancer mortality Non-lung cancer mortality, cohort study Epidemiology 



Dr. Gathirua-Mwangi is a postdoc appointee funded by a supplemental grant under R01CA196243 (PIs: Drs. Champion and Paskett). Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers 3R01CA196243-02S1, R25 CA117865-07S1 and K05CA175048.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10552_2016_843_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 KB)


  1. 1.
    Torre LA, Bray F, Sigel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:5–29. doi: 10.3322/caac.21262 CrossRefGoogle Scholar
  2. 2.
    Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65:5–29. doi: 10.3322/caac.21254 CrossRefPubMedGoogle Scholar
  3. 3.
    Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM et al (2011) National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 377:557–567. doi: 10.1016/S0140-6736(10)62037-5 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ligibel JA, Alfano CM, Courneya KS, Demark-Wahnefried W, Burger RA, Chlebowski RT, Fabian CJ et al (2014) American Society of Clinical Oncology position statement on obesity and cancer. J Clin Oncol 32:3568–3574. doi: 10.1200/JCO.2014.58.4680 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Demark-Wahnefried W, Platz EA, Ligibel JA, Blair CK, Courneya KS, Meyerhardt JA, Ganz PA et al (2012) The role of obesity in cancer survival and recurrence. Cancer Epidemiol Biomarkers Prev 21:1244–1259. doi: 10.1158/1055-9965.EPI-12-0485 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Goodwin PJ, Stambolic V (2015) Impact of the obesity epidemic on cancer. Annu Rev Med 66:281–296. doi: 10.1146/annurev-med-051613-012328 CrossRefPubMedGoogle Scholar
  7. 7.
    Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640–1645. doi: 10.1161/CIRCULATIONAHA.109.192644 CrossRefPubMedGoogle Scholar
  8. 8.
    McCullough AJ (2011) Epidemiology of the metabolic syndrome in the USA. J Dig Dis 12:333–340. doi: 10.1111/j.1751-2980.2010.00469.x CrossRefPubMedGoogle Scholar
  9. 9.
    Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB (2003) The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988–1994. Arch Intern Med 163:427–436. doi: 10.1001/archinte.163.4.427 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Rafaniello C, Panagiotakos DB et al (2013) Colorectal cancer association with metabolic syndrome and its components: a systematic review with meta-analysis. Endocr 44:634–647. doi: 10.1007/s12020-013-9939-5 CrossRefGoogle Scholar
  11. 11.
    Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Rafaniello C, Giugliano D (2013) Metabolic syndrome and postmenopausal breast cancer: systematic review and meta-analysis. Menopause 20:1301–1309. doi: 10.1097/GME.0b013e31828ce95d CrossRefPubMedGoogle Scholar
  12. 12.
    Teucher B, Rohrmann S, Kaaks R (2010) Obesity: focus on all-cause mortality and cancer. Maturitas 65:112–116. doi: 10.1016/j.maturitas.2009.11.018 CrossRefPubMedGoogle Scholar
  13. 13.
    Golabek T, Bukowczan J, Chlosta P, Powroznik J, Dobruch J, Borowka A (2014) Obesity and prostate cancer incidence and mortality: a systematic review of prospective cohort studies. Urol Int 92:7–14. doi: 10.1159/000351325 CrossRefPubMedGoogle Scholar
  14. 14.
    Dal Maso L, Zucchetto A, Talamini R, Serraino D, Stocco CF, Vercelli M, Falcini F et al (2008) Effect of obesity and other lifestyle factors on mortality in women with breast cancer. Int J Cancer 123:2188–2194. doi: 10.1002/ijc.23747 CrossRefPubMedGoogle Scholar
  15. 15.
    Adami HO, Trichopoulos D (2003) Obesity and mortality from cancer. N Engl J Med 348:1623–1624. doi: 10.1056/NEJMp030029 CrossRefPubMedGoogle Scholar
  16. 16.
    Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 348:1625–1638. doi: 10.1056/NEJMoa021423 CrossRefPubMedGoogle Scholar
  17. 17.
    Jaggers JR, Sui X, Hooker SP, LaMonte MJ, Matthews CE, Hand GA, Blair SN (2009) Metabolic syndrome and risk of cancer mortality in men. Eur J Cancer 45:1831–1838. doi: 10.1016/j.ejca.2009.01.031 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Lee JS, Cho SI, Park HS (2010) Metabolic syndrome and cancer-related mortality among Korean men and women. Ann Oncol 21:640–645. doi: 10.1093/annonc/mdp344 CrossRefPubMedGoogle Scholar
  19. 19.
    Stocks T, Van Hemelrijck M, Manjer J, Bjorge T, Ulmer H, Hallmans G, Lindkvist B et al (2012) Blood pressure and risk of cancer incidence and mortality in the Metabolic Syndrome and Cancer Project. Hypertension 59:802–810. doi: 10.1161/HYPERTENSIONAHA.111.189258 CrossRefPubMedGoogle Scholar
  20. 20.
    Seidell JC (2010) Waist circumference and waist/hip ratio in relation to all-cause mortality, cancer and sleep apnea. Eur J Clin Nutr 64:35–41. doi: 10.1038/ejcn.2009.71 CrossRefPubMedGoogle Scholar
  21. 21.
    Nago N, Ishikawa S, Goto T, Kayaba K (2011) Low cholesterol is associated with mortality from stroke, heart disease, and cancer: the Jichi Medical School Cohort Study. J Epidemiol 21:67–74. doi: 10.2188/jea.JE20100065 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Parekh N, Lin Y, Hayes RB, Albu JB, Lu-Yao GL (2010) Longitudinal associations of blood markers of insulin and glucose metabolism and cancer mortality in the third National Health and Nutrition Examination Survey. Cancer Causes Control 21:631–642. doi: 10.1007/s10552-009-9492-y CrossRefPubMedGoogle Scholar
  23. 23.
    Center for Disease Control and Prevention (2016) National health and nutrition examination survey data. Hyattsville, MD: National Centerf for Health Statistics. Accessed Jan 2016
  24. 24.
    Center for Disease Control and Prevention (1994) Plan and operation of the third national health and nutrition examination survey, 1988–94. Series 1: programs and collection procedures. Vital Health Stat 1(32):1–407Google Scholar
  25. 25.
    Bursac Z, Gauss H, Williams DK, Hosmer DW (2008) Purposeful selection of variables in logistic regression. Source Code Biol Med 2008:3. doi: 10.1186/1751-0473-3-17 Google Scholar
  26. 26.
    Beigh SH, Jain S (2012) Prevalence of metabolic syndrome and gender differences. Bioinformation 8: 613–616 doi: 10.6026/97320630008613 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Nation Center for Health Statistics (1996) Analytic and reporting guidelines: the third national health and nutrition examination survey, NHANES III (1988–94), vol 2015. Center for Disease Control and Prevention (CDC)Google Scholar
  28. 28.
    Younossi ZM, Zheng L, Stepanova M, Venkatesan C, Mir HM (2013) Moderate, excessive or heavy alcohol consumption: each is significantly associated with increased mortality in patients with chronic hepatitis C. Aliment Pharmacol Ther 37:703–709. doi: 10.1111/apt.12265 CrossRefPubMedGoogle Scholar
  29. 29.
    Grundmark B, Garmo H, Loda M, Busch C, Holmberg L, Zethelius B (2010) The metabolic syndrome and the risk of prostate cancer under competing risks of death from other causes. Cancer Epidemiol Biomarkers Prev 19:2088–2096. doi: 10.1158/1055-9965.EPI-10-0112 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Xiang YZ, Xiong H, Cui ZL, Jiang SB, Xia QH, Zhao Y, Li GB et al (2013) The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence. J Exp Clin Cancer Res 32:9. doi: 10.1186/1756-9966-32-9 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Bjorge T, Lukanova A, Jonsson H, Tretli S, Ulmer H, Manjer J, Stocks T et al (2010) Metabolic syndrome and breast cancer in the me-can (metabolic syndrome and cancer) project. Cancer Epidemiol Biomarkers Prev 19:1737–1745. doi: 10.1158/1055-9965.EPI-10-0230 CrossRefPubMedGoogle Scholar
  32. 32.
    Emaus A, Veierod MB, Tretli S, Finstad SE, Selmer R, Furberg AS, Bernstein L et al (2010) Metabolic profile, physical activity, and mortality in breast cancer patients. Breast Cancer Res Treat 121:651–660. doi: 10.1007/s10549-009-0603-y CrossRefPubMedGoogle Scholar
  33. 33.
    Lopez-Saez JB, Martinez-Rubio JA, Alvarez MM, Carrera CG, Dominguez Villar M, de Lomas Mier AG, Domenech C et al (2008) Metabolic profile of breast cancer in a population of women in southern Spain. Open Clin Cancer J 2:1–6. doi: 10.2174/1874189400802010001 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Batty GD, Shipley MJ, Marmot MG, Davey Smith G, Whitehall S (2003) Blood pressure and site-specific cancer mortality: evidence from the original Whitehall study. Br J Cancer 89:1243–1247. doi: 10.1038/sj.bjc.6601255 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Batty GD, Shipley MJ, Marmot M, Smith GD (2004) Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study. Cancer Causes Control 15:873–881. doi: 10.1007/s10552-004-1050-z CrossRefPubMedGoogle Scholar
  36. 36.
    Colangelo LA, Gapstur SM, Gann PH, Dyer AR, Liu K (2002) Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomarkers Prev 11:385–391 doi PubMedGoogle Scholar
  37. 37.
    Trevisan M, Liu J, Muti P, Misciagna G, Menotti A, Fucci F, Risk F et al (2001) Markers of insulin resistance and colorectal cancer mortality. Cancer Epidemiol Biomarkers Prev 10:937–941PubMedGoogle Scholar
  38. 38.
    Matthews CE, Sui X, LaMonte MJ, Adams SA, Hebert JR, Blair SN (2010) Metabolic syndrome and risk of death from cancers of the digestive system. Metabolism 59:1231–1239. doi: 10.1016/j.metabol.2009.11.019 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Marcus PM, Prorok PC, Miller AB, DeVoto EJ, Kramer BS (2015) Conceptualizing overdiagnosis in cancer screening. J Natl Cancer Inst 107: doi: 10.1093/jnci/djv014 PubMedPubMedCentralGoogle Scholar
  40. 40.
    Grossman E, Messerli FH, Boyko V, Goldbourt U (2002) Is there an association between hypertension and cancer mortality? Am J Med 112:479–486. doi: 10.1016/S0002-9343(02)01049-5 CrossRefPubMedGoogle Scholar
  41. 41.
    Dankner R, Shanik MH, Keinan-Boker L, Cohen C, Chetrit A (2012) Effect of elevated basal insulin on cancer incidence and mortality in cancer incident patients: the Israel GOH 29-year follow-up study. Diabetes Care 35:1538–1543. doi: 10.2337/dc11-1513 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Perseghin G, Calori G, Lattuada G, Ragogna F, Dugnani E, Garancini MP, Crosignani P et al (2012) Insulin resistance/hyperinsulinemia and cancer mortality: the Cremona study at the 15th year of follow-up. Acta Diabetol 49:421–428. doi: 10.1007/s00592-011-0361-2 CrossRefPubMedGoogle Scholar
  43. 43.
    Radisauskas R, Kuzmickiene I, Milinaviciene E, Everatt R (2016) Hypertension, serum lipids and cancer risk: a review of epidemiological evidence. Medicina (Kaunas) 52: 89–98. doi: 10.1016/j.medici.2016.03.002 CrossRefGoogle Scholar
  44. 44.
    Doyle SL, Donohoe CL, Lysaght J, Reynolds JV (2012) Visceral obesity, metabolic syndrome, insulin resistance and cancer. Proc Nutr Soc 71:181–189. doi: 10.1017/S002966511100320X CrossRefPubMedGoogle Scholar
  45. 45.
    Gallagher EJ, LeRoith D (2013) Epidemiology and molecular mechanisms tying obesity, diabetes, and the metabolic syndrome with cancer. Diabetes Care 36(Suppl 2):S233–S239. doi: 10.2337/dcS13-2001 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Suzuki R, Saji S, Toi M (2012) Impact of body mass index on breast cancer in accordance with the life-stage of women. Front. Oncol 2:123. doi: 10.3389/fonc.2012.00123 Google Scholar
  47. 47.
    Simpson E, Brown KA (2013) Obesity and breast cancer: role of inflammation and aromatase. J Mol Endocrinol. doi: 10.1530/JME-13-0217 PubMedGoogle Scholar
  48. 48.
    Hursting SD, Hursting MJ (2012) Growth signals, inflammation, and vascular perturbations: mechanistic links between obesity, metabolic syndrome, and cancer. Arterioscler Thromb Vasc Biol 32:1766–1770. doi: 10.1161/ATVBAHA.111.241927 CrossRefPubMedGoogle Scholar
  49. 49.
    Sridhar SS, Goodwin PJ (2009) Insulin-insulin-like growth factor axis and colon cancer. J Clin Oncol 27:165–167. doi: 10.1200/JCO.2008.19.8937 CrossRefPubMedGoogle Scholar
  50. 50.
    Belardi V, Gallagher EJ, Novosyadlyy R, Leroith D (2013) Insulin and IGFs in Obesity-Related Breast Cancer. J Mammary Gland Biol Neoplasia. doi: 10.1007/s10911-013-9303-7 PubMedGoogle Scholar
  51. 51.
    Klil-Drori AJ, Azoulay L, Pollak MN (2016) Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing? Nat Rev Clin Oncol. doi: 10.1038/nrclinonc.2016.120 PubMedGoogle Scholar
  52. 52.
    Hua F, Yu JJ, Hu ZW (2016) Diabetes and cancer, common threads and missing links. Cancer Lett 374:54–61. doi: 10.1016/j.canlet.2016.02.006 CrossRefPubMedGoogle Scholar
  53. 53.
    Hoenerhoff MJ (2015) Inflammation and cancer: Partners in crime. Vet J 206:1–2. doi: 10.1016/j.tvjl.2015.07.007 CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Department of Epidemiology, Richard M. Fairbanks School of Public HealthIndiana UniversityIndianapolisUSA
  2. 2.Indiana University Melvin and Bren Simon Cancer CenterIndianapolisUSA
  3. 3.Department of BiostatisticsIndiana University School of MedicineIndianapolisUSA

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