Visceral Fat Area and Markers of Insulin Resistance in Relation to Colorectal Neoplasia

OBJECTIVE

Although abdominal obesity and related metabolic abnormalities are hypothesized to promote colorectal carcinogenesis, direct confirmation of this effect is required. Here, we examined the relation of early-stage colorectal neoplasia to visceral fat area and markers of insulin resistance.

RESEARCH DESIGN AND METHODS

Subjects were participants in a comprehensive health screening conducted at the Hitachi Health Care Center, Ibaraki, Japan. During a 3-year period (2004–2007), a total of 108 patients with early-stage colorectal neoplasia, including 22 with early cancer, were identified among individuals who received both colorectal cancer screening and abdominal computed tomography scanning. Three control subjects matched to each case subject were randomly selected from those whose screening results were negative. Conditional logistic regression analysis was used to examine the association of measures of obesity and markers of insulin resistance with colorectal neoplasia, with adjustment for smoking and alcohol drinking.

RESULTS

Visceral fat area, but not subcutaneous fat area, was significantly positively associated with colorectal cancer, with odds ratios (95% CI) for the lowest to highest tertile of visceral fat area of 1 (reference), 2.17 (0.45–10.46), and 5.92 (1.22–28.65), respectively (P^trend = 0.02). Markers of insulin resistance, particularly fasting glucose, were also positively associated with colorectal cancer risk. In contrast, no associations were observed for colorectal adenomas.

CONCLUSIONS

These results suggest that visceral adipose tissue accumulation and insulin resistance may promote the development of early-stage cancer but not adenoma in the colorectum.Although the role of obesity as a strong predictor of various chronic diseases, including type 2 diabetes and cardiovascular disease, has been established, accumulating evidence also indicates the importance of obesity and its related metabolic disorders in the development of cancer (1). In Japan, the incidence of colorectal cancer has sharply increased over the last several decades and is now among the highest in the world (2). This time trend, as well as findings from migrant studies (3), suggests the involvement of environmental factors in colorectal carcinogenesis. Epidemiological studies (4,5) have shown that colorectal cancer risk is more strongly associated with waist circumference than with BMI, indicating the etiological importance of abdominal or visceral fat disposition, rather than overall adiposity. However, given that waist circumference is only a surrogate of visceral fat mass, more direct evidence is required before the link between visceral adiposity and cancer risk can be considered conclusive.Several studies have assessed the association between visceral fat area, as measured using computed tomography (CT) scanning, and colorectal neoplasia (6–10), but results have been mixed. For example, a Japanese study (7) demonstrated an increased prevalence of colorectal adenomas among individuals with higher visceral fat area, whereas a larger, more recent study (8) did not. Given that adenomatous polyps are common but only a minority progress to cancer (11), the association with cancer should also be explored, but evidence to date is sparse. In a Turkish study (10), patients with colorectal cancer tended to have a smaller rather than larger visceral fat area than that in control subjects. This unexpected finding may have been due to weight loss in the course of cancer development, however, a possibility that highlights the importance of assessing visceral fat before the diagnosis of cancer or development of symptoms.An insulin hypothesis has been proposed to explain the observed association between obesity or abdominal obesity and colorectal neoplasia (12,13). Accumulation of visceral fat is a strong determinant of insulin resistance and hyperinsulinemia (14) and, as experimental data show (15), insulin promotes colorectal carcinogenesis. Compatible with the insulin hypothesis, epidemiological data appear consistent in showing a positive association between colorectal neoplasia and markers of hyperinsulinemia or insulin resistance (rev. in 16). These findings notwithstanding, however, a role for insulin resistance in promoting the development of adenoma, cancer, or both in the colorectum has yet to be confirmed. To further explore these issues, we examined the relation of visceral fat mass assessed by CT and measures of insulin resistance to adenoma and cancer in the colorectum among asymptomatic individuals who underwent screening.