Is Diabetes a Risk Factor for Colorectal Cancer?

Abstract

Throughout the world, adoption of a Western life style has paralleled an increase in the incidence of both type 2 diabetes mellitus and colorectal cancer. This is perhaps not surprising, as the major environmental determinants for type 2 diabetes, including body mass index (BMI), central obesity, physical inactivity, and Western dietary patterns are remarkably consistent with the constellation of risk factors that have been identified for colorectal cancer. Perhaps what has been less clear is whether diabetes, independent of these other risk factors, influences the risk of colorectal cancer. If so, such a finding would have potential implications for more vigorous lifestyle modification or cancer screening of individuals with type 2 diabetes. Moreover, understanding the mechanistic basis for such an association may provide fresh insights into the pathogenesis of both conditions.A number of early studies reported a higher risk of colon cancer among individuals with diabetes. These studies were limited by small sample size, reliance on death certificates and autopsies for endpoint ascertainment, and inability to control for important confounders including BMI and physical inactivity [1][2][3][4]. As such, it was difficult to determine if the association between diabetes and colorectal cancer was merely a reflection of the greater prevalence of known lifestyle risk factors for cancer among those with diabetes. However, more recent high quality prospective studies have shown a significant, albeit more modest association between diabetes and risk of colorectal cancer even after accounting for shared risk factors for both diseases. One of these large, prospective studies, the Cancer Prevention Study, included 866,793 individuals, 15,847 of whom had diabetes [5]. Over 13 years of follow-up, an increased risk of colorectal cancer, even after accounting for BMI and physical inactivity, was noted in men with diabetes (RR = 1.30; 95 % CI 1.03-1.65) and a modest non-significant elevation was seen in women with diabetes (RR = 1.16; 95 % CI 0.87-1.53). In the Nurses' Health Study, diabetes was similarly associated with an increase in the risk of colon cancer after adjustment for BMI and physical activity (multivariate-adjusted RR = 1.49; 95 % CI 1.09-2.06) [6]. By 2005, several case-control and cohort studies had examined this relationship, which was systematically reviewed by Larsson et al. [7]. In their metaanalysis of 6 case-control and 9 cohort studies encompassing more than 2 million participants, a history of diabetes was associated with an increased risk of colorectal cancer (summary RR = 1.30, 95 % CI 1.20-1.40). The results did not vary according to study design, geographic origin (United States vs. Europe), sex, or cancer site.However, not all subsequent studies have been consistent. In the Cancer Prevention Study II Nutrition Cohort, Campbell et al. [8] found a moderate increase in risk of colorectal cancer among men with diabetes (pooled RR = 1.24; 95 % CI 1.08-1.44), but no such association among women. Inoue et ...

HbA1c showed a positive association with carcinoembryonic antigen (CEA) level in only diabetes, not prediabetic or normal individuals

“…Surrogate markers of hyperinsulinemia, such as postprandial C‐peptide and nonfasting insulin, are more strongly associated with colorectal cancer. Increased circulating insulin might stimulate the growth of aberrant crypt foci and increase the number and size of tumors . Other gastrointestinal tumor markers, such as CA 19‐9, have also been reported to be elevated in diabetic patients and to have a positive correlation with HbA1c .…”

“…21 Increased circulating insulin might stimulate the growth of aberrant crypt foci and increase the number and size of tumors. 22 Other gastrointestinal tumor markers, such as CA 19-9, have also been reported to be elevated in diabetic patients and to have a positive correlation with HbA1c. 23 Although the mechanism underlying the positive correlation between CA 19-9 levels and HbA1c in diabetic patients remains unclear, the authors claimed that CA 19-9 might be released by exocrine pancreatic ductal cells damaged from glucose toxicity in poorly controlled diabetic patients.…”

Poly(3-hydroxybutyrate-CO-3-hydroxyvalerate) PHBHV biocompatible nanocarriers for 5-FU delivery targeting colorectal cancer

“…Worldwide, an increasing risk for developing colorectal cancer is determined by aggravating factors such as, primarily, the occurrence of inflammatory bowel disease as well as the incidence of obesity and type 2 diabetes, all associated with additional consumption of heavily calorie-laden and highly processed food accompanied by the widely spread lack of exercise (Meyerhardt et al., 2003; Jemal et al., 2008; Khalili & Chan, 2012; Khalili et al., 2015).…”

Management of colorectal cancer and diabetes

“…14 Elevated levels of both circulating postprandial insulin and C-peptide have also been associated with an increase colorectal cancer risk in three large studies. 15,16 The role of exogenous insulin in colorectal cancers is controversial as there are several studies that support the theory that exogenous insulin increases colorectal cancer 2,3 but others that refute this claim. 17 A recent systematic review concludes that while diabetes mellitus increases the risk of colorectal cancer, the use of insulin therapy may also increase this risk.…”