Abstract
Metabolic syndrome is associated with increased cancer risk and progression at almost all sites, including the prostate in high-stage prostate cancer. However, several reports have described an inverse relationship between metabolic syndrome and its components and low-stage incident prostate cancer. Such anomalies in cancer research hamper efforts to fight cancer. Evidence suggests that metabolic syndrome and its components have two distinct effects in prostate cancer, concealing prostate cancer in low-stage disease and promoting progression to high-stage incident, nonlocalized, and lethal prostate cancer. The concealment of prostate cancer by metabolic syndrome and its components might be related to bias mechanisms that reduce PSA level and lead to a delayed diagnosis of low-stage prostate cancer, meaning that fewer men with metabolic syndrome are diagnosed with low-stage disease. The inverse link between metabolic syndrome and its components and low-stage incident prostate cancer might simply be the result of such bias and the shortcomings of the diagnostic procedure rather than being related to prostate cancer biology itself. The evidence summarized here supports the hypothesis that the link between metabolic syndrome and its components and incident prostate cancer is a two-way and stage-dependent one, a theory that requires further research.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Zhou, J. R., Blackburn, G. L. & Walker, W. A. Symposium introduction: metabolic syndrome and the onset of cancer. Am. J. Clin. Nutr. 86, s817–s819 (2007).
Esposito, K., Chiodini, P. & Colao, A. M. Metabolic syndrome and risk of cancer. Diabetes Care 35, 2402–2411 (2012).
De Nunzio, C. W. et al. The correlation between metabolic syndrome and prostatic diseases. Eur. Urol. 61, 560–570 (2012).
Laukkanen, J. A. et al. Metabolic syndrome and the risk of prostate cancer in Finnish men: a population-based study. Cancer Epidemiol. Biomarkers Prev. 13, 1646–1650 (2004).
Lund, H. L. et al. Metabolic syndrome predicts prostate cancer in a cohort of middle-aged Norwegian men followed for 27 years. Ann. J. Epidemiol. 164, 769–764 (2006).
Beebe-Dimmer, J. L. et al. Racial differences in risk of prostate cancer associated with the metabolic syndrome. Urology 74, 185–190 (2009).
Hammarsten, J. & Peeker, R. Urological aspects of the metabolic syndrome. Nat. Rev. Urol. 8, 483–494 (2011).
Häggström, C. et al. Prospective study on metabolic factors and risk of prostate cancer. Cancer 118, 6199–6299 (2012).
Tande, A. J., Platz, E. A. & Folsom, A. R. The metabolic syndrome is associated with reduced risk of prostate cancer. Am. J. Epidemiol. 164, 1094–1102 (2006).
Stocks, T. et al. Blood pressure, body size and prostate cancer risk in the Swedish Construction Workers cohort. Int. J. Cancer 127, 1660–1668 (2010).
Fall, K. et al. Diabetes mellitus and prostate cancer risk; a nationwide case-control study within PCBaSe Sweden. Cancer Epidemiol. Biomarkers Prev. 22, 1102–1109 (2013).
Stocks, T. et al. Insulin resistance is inversely related to prostate cancer: a prospective study in Northern Sweden. Int. J. Cancer 120, 2678–2686 (2007).
Gong, Z. et al. Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer prevention trail. Cancer Epidemiol. Biomarkers Prev. 15, 1977–1983 (2006).
Albanes, D. et al. Serum 25-hydroxy vitamin D and prostate cancer risk in a large nested case-control study. Cancer Epidemiol. Biomarkers Prev. 20, 1850–1860 (2011).
Yun, S. J. et al. Elevated insulin and insulin resistance are associated with advanced pathological stage of prostate cancer in Korean population. J. Kor. Med. Sci. 27, 1079–1084 (2012).
Zuh, K. et al. History of diabetes mellitus and risk of prostate cancer in physicians. Am. J. Epidemiol. 159, 978–982 (2004).
Tsilidis, K. K. et al. Diabetes mellitus and risk of prostate cancer in the European prospective investigation into cancer and nutrition. Int. J. Cancer 136, 372–381 (2015).
Möller, H. et al. Prostate cancer incidence, clinical stage and survival in relation to obesity: a prospective cohort study in Denmark. Int. J. Cancer 136, 1940–1947 (2015).
Lai, G. Y. et al. Association between C-peptide concentration and prostate cancer incidence in the CLUE II cohort study. Cancer Prev. Res. (Phila). 3, 1334–1341 (2010).
Meyer, H. E. et al. Vitamin D, season, and risk of prostate cancer: a nested case-control study within Norwegian health studies. Am. J. Clin. Nutr. 97, 147–154 (2013).
Discacciati, A. et al. Body mass index in early and middle-late adulthood and risk of localized, advanced and fatal prostate cancer: a population-based prospective study. Br. J. Cancer 105, 1061–1068 (2011).
Coker, A. L. et al. Diabetes mellitus and prostate cancer risk among older men: population-based case control-study. Br. J. Cancer 90, 2171–2175 (2004).
Pierce, B. L. et al. Diabetes mellitus and prostate cancer risk. Prostate 68, 1126–1132 (2008).
Wright, M. E. et al. Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality. Cancer 109, 675–684 (2007).
Calton, B. A. et al. History of diabetes mellitus and subsequent prostate cancer risk in the NIH-AARP diet and health study. Cancer Causes Control 18, 493–503 (2007).
Morote, J. et al. Metabolic syndrome increases the risk of aggressive prostate cancer detection. BJU Int. 111, 1031–1036 (2012).
Turner, E. L. et al. Association of diabetes mellitus with prostate cancer: nested case control study (prostate testing for cancer and treatment study). Int. J. Cancer 128, 440–446 (2011).
Zhang, G.-M. et al. The association between metabolic syndrome and advanced prostate cancer in Chinese patients receiving radical prostatectomy. Asian J. Androl. 17, 839–844 (2015).
Hammarsten, J. & Högstedt, B. Clinical, haemodynamic, anthropometric, metabolic and insulin profile of men with high stage and high grade clinical prostate cancer. Blood Press. 13, 47–55 (2004).
Grundmark, B. et al. The metabolic syndrome and the risk of prostate cancer under competing risks of death from other causes. Cancer Epidemiol. Biomarkers Prev. 19, 2088–2096 (2010).
Hammarsten, J. et al. A higher prediagnostic insulin level is a prospective risk factor for incident prostate cancer. Cancer Epidemiol. 34, 574–579 (2010).
Albanes, D. et al. Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. J. Natl Cancer Inst. 101, 1272–1279 (2009).
Hsing, A. W. et al. Body size and prostate cancer: a population-based case-control study in China. Cancer Epidemiol. Biomarkers Prev. 9, 1335–1341 (2000).
Hsing, A. W. et al. Prostate cancer risk and serum levels of insulin and leptin: a population-based study. J. Natl Cancer Inst. 93, 783–789 (2001).
Hsing, A. W. et al. Insulin resistance and prostate cancer risk. J. Natl Cancer Inst. 95, 67–71 (2003).
Michalakis, K. et al. Serum adiponectin concentrations and tissue expression of adiponectin receptors are reduced in patients with prostate cancer. Cancer Epidemiol. Biomarkers Prev. 16, 308–313 (2007).
Kheterpal, E. et al. Effect of metabolic syndrome on pathological features of prostate cancer. Urol. Oncol. 31, 1054–1059 (2013).
Pischon, T. et al. Body size and risk of prostate cancer in the European prospective Investigation into cancer and nutrition. Cancer Epidemiol. Biomarkers Prev. 17, 3252–3261 (2008).
Giovannucci, E. et al. Risk factors for prostate cancer incidence and progression in the health professionals follow-up study. Int. J. Cancer 121, 1571–1578 (2007).
Putman, S. D. et al. Lifestyle and anthropometric risk factors for prostate cancer in a cohort of Iowa men. Ann. Epidemiol. 10, 361–369 (2000).
De Nunzio, C. et al. Metabolic syndrome is associated with advanced prostate cancer in patients treated with radical retropubic prostatectomy: results from a multicenter prospective study. BMC Cancer 16, 407 (2016).
Hammarsten, J. & Högstedt, B. Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer. Eur. J. Cancer 41, 2887–2895 (2005).
Ma, J. et al. Prediagnostic body-mass index, plasma C-peptide concentration, and prostate-specific mortality in men with prostate cancer: a long-term survival analysis Lancet Oncol. 9, 1039–1047 (2008).
Laaksonen, D. E. et al. Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur. J. Endocrinol. 149, 601–608 (2003).
Laaksonen, D. E. et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 27, 1036–1034 (2004).
Traish, A. M. Adverse health effects of testosterone deficiency (TD) in men. Steroids 88, 106–116 (2014).
Rhoden, E. L. & Morgenthaler, A. Influence of demographic factors and biochemical characteristics on the prostate specific antigen (PSA) response to testosterone replacement therapy. Int. J. Impot. Res. 18, 201–205 (2006).
Ohwaki, K., Endo, F., Muraishi, O., Hiramatsu, S. & Yano, E. Relationship between prostate-specific antigen and hematocrit: does hemodilution lead to a lower PSA concentration in men with a higher body mass index? Urology 75, 648–653 (2010).
Hammarsten, J., Högstedt, B., Holthuis, N. & Mellström, D. Components of the metabolic syndrome – risk factors for the development of benign prostatic hyperplasia. Prostate Cancer Prostate Dis. 1, 157–162 (1998).
Ozden, C. et al. The correlation between metabolic syndrome and prostatic growth in patients with benign prostatic hyperplasia. Eur. Urol. 51, 199–203 (2007).
Karlsen, R. V. et al. PSA testing without clinical indication for prostate cancer in relation to socio-demographic and clinical characteristics in the Danish Diet, Cancer and Health Study. Acta Oncol. 52, 1609–1614 (2013).
Wiren, S. M. et al. Fatherhood status and risk of prostate cancer: nationwide population-based case control study. Int. J. Cancer 133, 937–943 (2013).
Perel, P. et al. Household wealth and the metabolic syndrome in the Whitehall II study. Diabetes Care 29, 2694–2700 (2006).
McLaren, L. Socioeconomic status and obesity. Epidemiol. Rev. 29, 29–48 (2007).
Agardh, E., Allebeck, P., Hallqvist, J., Moradi, T. & Sidochuk, A. Type 2 diabetes incidence and socio-economic position: a systematic review and metaanalysis. Int. J. Epidemiol. 40, 804–818 (2011).
Murtola, T. J. et al. Antidiabetic medication and prostate cancer risk: a population-based case-control study. Am. J. Epidemiol. 168, 925–931.
Nordström, T. et al. The risk for prostate cancer for men on aspirin, statin and antidiabetic medications. Eur. J. Cancer 51, 725–733 (2015).
Häggström, C. et al. Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs an risk of prostate cancer. Int. J. Cancer 140, 611–617 (2017).
Roddam, A. W. et al. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J. Natl Cancer Inst. 100, 170–183 (2008).
Reavan, G. M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37, 1595–1607 (1988).
DeFronzo, R. A. & Ferrannini, E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14, 173–194 (1991).
Haffner, S. M. et al. Prospective analysis of the insulin-resistance syndrome (Syndrome X). Diabetes 41, 715–789 (1992).
Hanahan, D. & Weinberg, R. A. Hallmarks of cancer. Cell 144, 646–674 (2011).
Golden, S. H., Robinson, K. A., Saldanha, I., Anton, B. & Ladenson, P. W. Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive study. J. Clin. Endocrinol. Metab. 94, 1853–1878 (2009).
Gacci, M. et al. Meta-analysis of metabolic syndrome and prostate cancer. Prostate Cancer Prostatic Dis. 20, 146–1552017 (2017).
Jahn, J. L., Giovannucci, E. L. & Stampfer, M. J. The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology and treatment of prostate cancer in the prostate-specific antigen era. Int. J. Cancer 137, 2795–2802 (2015).
Tuomilehto, J. et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N. Engl. J. Med. 344, 1343–1350 (2001).
Feinman, R. D. et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition 31, 1–13 (2015).
Accurso, A. et al. Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for critical appraisal. Nutr. Metab. (Lond.). 5, 9 (2008).
Mansoor, N. et al. Effects of carbohydrate diets v. low fat diets on body weight and cardiovascular risk factors: a metaanalysis of randomized controlled trials. Br. J. Nutr. 115, 466–479 (2016).
Noakes, M. et al. Comparison of isocaloric very low carbohydrate/high saturated fat and high carbohydrate/low saturated fat diets on body composition and cardiovascular risk. Nutr. Metab. (Lond.). 3, 7 (2006).
Boden, G. et al. Effect of low-carbohydrate diet on appetite, blood glucose levels and insulin resistance in obese patients with type 2 diabetes. Ann. Intern. Med. 142, 403–411 (2005).
Venkateswaran, V. et al. Association of diet-induced hyperinsulinemia with accelerated growth of prostate cancer (LNCaP) xenografts. J. Natl Cancer Inst. 99, 1793–1800 (2007).
Manheimer, E. W. et al. Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis. Am. J. Clin. Nutr. 102, 922–932 (2015).
Author information
Authors and Affiliations
Contributions
J.H. performed the research and wrote the manuscript. J.-E.D., M.H., D.M., and R.P. reviewed and edited the article before submission.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Hammarsten, J., Damber, JE., Haghsheno, M. et al. A stage-dependent link between metabolic syndrome components and incident prostate cancer. Nat Rev Urol 15, 321–333 (2018). https://doi.org/10.1038/nrurol.2018.8
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrurol.2018.8
This article is cited by
-
Metabolic syndrome and its pharmacologic treatment are associated with the time to castration-resistant prostate cancer
Prostate Cancer and Prostatic Diseases (2022)
-
Androgens, aging, and prostate health
Reviews in Endocrine and Metabolic Disorders (2022)
-
Prostate cancer management: long-term beliefs, epidemic developments in the early twenty-first century and 3PM dimensional solutions
EPMA Journal (2020)
-
Evaluation of serum fatty acid binding protein-4 (FABP-4) as a novel biomarker to predict biopsy outcomes in prostate biopsy naïve patients
International Urology and Nephrology (2020)