The clustering of atherosclerotic risk factors that identify metabolic syndrome was first recognized in 1983 [1
]. In 1988, Reaven [2
] introduced the term syndrome X
, in which insulin resistance (IR) was the common denominator. In 1998, the World Health Organization recommended a unifying definition and chose the term metabolic syndrome [3
], primarily because the available data did not support IR as the cause of all of the components of this syndrome [4
Metabolic syndrome is now recognized as a cluster of metabolic abnormalities and is defined as the presence of three or more of the following factors: abdominal obesity (increased waist circumference), elevated triglycerides, low high-density lipoprotein (HDL) cholesterol, high blood pressure, and high fasting glucose [5
IR, along with its associated hyperinsulinemia and hyperglycemia, and adipocyte cytokines (adipokines) may lead to vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease (CVD) [2
The metabolic syndrome involves a proinflammatory, prothrombotic state and is associated with elevated levels of C-reactive protein [9
], interleukin (IL)-6 [12
], and plasminogen activator inhibitor (PAI)-1 [13
]. These inflammatory and prothrombotic markers are also associated with an increased risk for subsequent CVD and type 2 diabetes [11
In addition to the mechanical effects of obesity, such as an increase in intra-abdominal pressure caused by excess adipose tissue, adipose tissue secretes various adipokines, such as tumor necrosis factor (TNF), IL-6, leptin, and insulin-like growth factor-1 (IGF-1), which are considered to have pathogenic effects in relation to gastrointestinal cancer.
The classification of obesity for epidemiological purposes defines overweight as body mass index (BMI) >25
and obesity as BMI >30
]. Fat is principally deposited in two compartments—subcutaneous and central depots. It is thought that central fat (i.e., visceral fat) is more metabolically active than peripheral subcutaneous fat [15
In the Asian Cohort Consortium, the East Asian, Indian, and Bangladeshi populations with a BMI <20.1
had significantly higher mortality compared with subjects with a BMI of 22.6–25
]. Mortality was lowest among men and women with a BMI in the range of 22.6–27.5
Omental adipose tissue, also referred to as visceral adipose tissue, can exert systemic effects that are putatively involved in cancer biology [18
]. Metabolic syndrome is defined based on a cluster of abnormal clinical factors that have been associated with the development of CVD morbidity [19
] and type 2 diabetes mellitus [20
]. The definitions used in this paper are summarized in [3
Definitions of metabolic syndrome.
Overall, 14% of all cancer deaths in men and 20% of all cancer deaths in women are attributable to overweight and obesity [29
]. Obesity is associated with increased mortality arising from cancers of the prostate and stomach in men; of the breast (postmenopausal), endometrium, cervix, uterus, and ovaries in women; and of the kidney (renal cell), colon, esophagus (adenocarcinoma), pancreas, gallbladder, and liver in both sexes [29
]. However, the relationship between metabolic syndrome and the pathogenesis of cancer is less well established.
Here, we review the association between metabolic syndrome and gastrointestinal cancer, focusing on the pathogenic roles of obesity and adipokines.