Metabolic syndrome and risk of death from cancers of the digestive system

Abstract

We tested the hypothesis that risk of early mortality from cancers of the digestive system will be greater in men with, compared with men without, the metabolic syndrome (MetS). Participants were 33 230 men who were seen at the Cooper Clinic in Dallas, TX, and followed for 14.4 (SD = 7.0) years. Metabolic syndrome was defined as having at least 3 of the following risk factors: abdominal obesity, fasting hypertriglyceridemia, low high-density lipoprotein cholesterol, high blood pressure, or high fasting glucose level or diabetes. Metabolic syndrome was associated with higher mortality (hazard ratio [HR] = 1.90 [95% confidence interval = 1.42-2.55]), and there was a graded positive association for the addition of more syndrome components (P < .01). Adjustment for cardiorespiratory fitness attenuated the risk estimates by 20% to 30%, but they remained significant after this adjustment. Evaluation of the independent contribution of each of the syndrome components revealed that both abdominal obesity (HR = 1.89 [1.36-2.62]) and high glucose (HR = 1.38 [1.02-1.87]) were independently associated with cancer mortality. Our results support the hypothesis that metabolic syndrome is positively associated with mortality from cancers of the digestive system. Interventions that reduce abnormalities associated with the syndrome could reduce risk of premature death from these cancers.

Introduction

Cancers of the digestive system will result in more than 270 000 deaths in the United States in 2007, and this represents nearly 25% of all deaths from cancer in this period [1]. Cancers of the digestive system include those of the alimentary canal below the neck (eg, esophagus, stomach, small and large intestines) and key digestive organs (ie, pancreas, liver, gallbladder). Whereas the 5-year survival rates are nearly 90% or greater for breast and prostate cancer, the survival rate for digestive cancers as a group is only 45% [2]. Therefore, identification of modifiable risk factors for these more lethal cancers may provide important opportunities for reducing overall cancer mortality.

The metabolic syndrome (MetS) is a condition that has been defined as a clustering of at least 3 of 5 cardiovascular and diabetes risk factors, including: abdominal obesity, elevated fasting blood glucose, elevated blood pressure, hypertriglyceridemia, and low levels of high density lipoprotein (HDL) [3]. The prevalence of MetS in the United States is approximately 24% for all adults but is greater than 40% for those older than 60 years [4], the age group in which the majority of cancers develop. The prevalence of MetS for those with diabetes is greater than 60% [5].

Metabolic syndrome represents the development of central adiposity and abnormalities in carbohydrate and lipid metabolism as a consequence of genetic predisposition coupled with sedentary lifestyles and poor dietary habits [3], [6]. Hallmark features associated with MetS are hyperinsulinemia and low-level, chronic inflammation [6], both of which are believed to play an important role in the development and growth of invasive cancers [7]. Indeed, recent investigations have indicated a positive association between clusters of the MetS components and adenomatous polyps [8], and incident [9], [10], [11] and fatal colon cancer outcomes [12], [13]. In addition, positive associations between pancreatic cancer and elements of the syndrome, including abdominal obesity [14], [15], hyperinsulinemia [16], and elevated glucose [16], [17], also have been reported.

There is substantial evidence that clusters of the MetS components are positively associated with risk for early mortality [18], [19], cardiovascular disease [18], [20], [21], [22], and diabetes [21], [23]. However, fewer studies have estimated the risk associated with cancer outcomes using standardized definitions of MetS that are now frequently used in clinical practice. For this reason, our current understanding of the degree to which MetS is associated with the risk of cancer outcomes remains incomplete.

Accordingly, the purpose of this investigation was to (1) test the hypothesis that risk of early mortality from cancers of the digestive system will be greater in those with, compared with those without, MetS and (2) to estimate the risk associated with a higher number of MetS components on mortality from these cancers. Results from this study provide important translational insight into risk for cancer mortality relative to commonly measured clinical metabolic risk factors.