Metabolic Syndrome and Risk of Cancer

A Systematic Review and Meta-analysis

Katherine Esposito, MD, PHD; Paolo Chiodini, PHD; Annamaria Colao, MD; Andrea Lenzi, MD; Dario Giugliano, MD, PHD


Diabetes Care. 2012;35(11):2402-2411. 

In This Article

Abstract and Introduction


Objective—Available evidence supports the emerging hypothesis that metabolic syndrome may be associated with the risk of some common cancers. We did a systematic review and meta-analysis to assess the association between metabolic syndrome and risk of cancer at different sites.
Research Design and Methods—We conducted an electronic search for articles published through October 2011 without restrictions and by reviewing reference lists from retrieved articles. Every included study was to report risk estimates with 95% CIs for the association between metabolic syndrome and cancer.
Results—We analyzed 116 datasets from 43 articles, including 38,940 cases of cancer. In cohort studies in men, the presence of metabolic syndrome was associated with liver (relative risk 1.43, P < 0.0001), colorectal (1.25, P < 0.001), and bladder cancer (1.10, P = 0.013). In cohort studies in women, the presence of metabolic syndrome was associated with endometrial (1.61, P = 0.001), pancreatic (1.58, P < 0.0001), breast postmenopausal (1.56, P = 0.017), rectal (1.52, P = 0.005), and colorectal (1.34, P = 0.006) cancers. Associations with metabolic syndrome were stronger in women than in men for pancreatic (P = 0.01) and rectal (P = 0.01) cancers. Associations were different between ethnic groups: we recorded stronger associations in Asia populations for liver cancer (P = 0.002), in European populations for colorectal cancer in women (P = 0.004), and in U.S. populations (whites) for prostate cancer (P = 0.001).
Conclusions—Metabolic syndrome is associated with increased risk of common cancers; for some cancers, the risk differs betweens sexes, populations, and definitions of metabolic syndrome.


The metabolic syndrome is a cluster of risk factors for cardiovascular disease and type 2 diabetes and constitutes a growing problem worldwide.[1] These factors include obesity (particularly central adiposity), dysglycemia, raised blood pressure, elevated triglyceride levels, and low HDL cholesterol levels. On the basis of the most recent epidemiological analysis using the American Heart Association/National Heart, Lung, and Blood Institute 2005 guidelines, similar to those of National Cholesterol Education Program/Adult Treatment Panel III, slightly more than one-third (35%) of adults in the U.S. could be characterized as having the metabolic syndrome.[1] This translates to nearly 80 million U.S. adults affected by the syndrome (calculated from U.S. Bureau of the Census data for 2007, with an adult resident population of 228 million). A higher percentage (40.1%) of prevalence occurred with revised International Diabetes Federation 2005 criteria, which use a lower cutoff point for waist (≥94 cm in men and ≥80 cm in women).

Available evidence from epidemiologic investigations and experimental, translational, and clinical studies supports the emerging hypothesis that metabolic syndrome may be an important etiologic factor for the development and progression of certain types of cancer and also for overall cancer mortality.[2] Differences in the study populations, length of follow-up, sample sizes, frequency of events, study end points, and statistical adjustment for confounding may all have contributed to the conflicting patterns of association seen in earlier studies. Moreover, both obesity[3] and diabetes[4] have repeatedly been associated with increased incidence for some common cancers, and both conditions represent two important factors contributing to the prevalence of the metabolic syndrome. There is also some evidence that dyslipidemia (low HDL cholesterol levels and/or raised triglyceride) is associated with some cancers.[5] It therefore remains possible that some of the associations between metabolic syndrome and cancer risk may be mediated by the coexistence of obesity and overt diabetes.

A systematic and quantitative assessment of published studies is not available. Therefore, we conducted a meta-analysis to summarize all published studies to date on the incidence of cancer associated with metabolic syndrome.