Gender difference in the association of insulin and the insulin-like growth factor axis with colorectal neoplasia

Abstract

Objective: Accumulating evidence has implicated insulin and the insulin-like growth factor (IGF) axis in colorectal carcinogenesis. Of interest, adiposity is likely to impose a greater risk on men than on women, which indicates that the association of insulin and the IGF axis with colorectal neoplasia may differ by gender. However, epidemiological evidence for this possible gender difference is limited to date. Methods: We measured plasma concentrations of C-peptide, IGF-I and IGF-binding proteins (IGFBPs) 1 and 3 in 1520 healthy volunteer examinees who underwent total colonoscopy between February 2004 and February 2005, and cross-sectionally investigated the association of these biomarkers with colorectal adenoma by gender. An unconditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for colorectal adenoma after adjustment for potential confounders. Results: We observed a positive association of C-peptide and IGF-I (P trend o0.001 and 0.02, respectively) and an inverse association of IGFBP-1 (P trend ¼ 0.002) with colorectal adenoma in men. Adjusted ORs of colorectal adenoma for the highest compared with the lowest quartile were also statistically significant for C-peptide (OR: 2.62, 95% CI: 1.71-4.01), IGF-I (OR: 1.63, 95% CI: 1.08-2.46) and IGFBP-1 (OR: 0.49, 95% CI: 0.32-0.75). In contrast, no measurable association was seen in women. Corresponding ORs for C-peptide, IGF-I and IGFBP-1 were 0.98 (95% CI: 0.56-1.71), 0.79 (95% CI: 0.44-1.43) and 1.05 (95% CI: 0.60-1.86), respectively. The gender difference was statistically significant for C-peptide (P interaction ¼ 0.03) and marginally significant for IGF-I and IGFBP-1 (P interaction ¼ 0.14 and 0.12, respectively). Conclusion: Our observations suggest that insulin and the IGF axis act differently by gender in colorectal carcinogenesis, at least in its early stage. The findings of this study further our understanding of the complexities of the gender difference in the association between adiposity and colorectal neoplasia.

Metabolically-healthy obesity is associated with higher prevalence of colorectal adenoma

“…Several genetic and epigenetic factors have been suggested to explain sex-specific differences in CRC risk [38]. Insulin and insulin-like growth factor axis may act differently by sex in CRC carcinogenesis [39]. Our findings suggest that adiposity may impose a different risk on CRC by sex, which warrants further investigation.…”

Obesity and colorectal adenomatous polyps: A cross-sectional study in Korean adults

“…Estrogen may exert a protective effect through the insulin/IGF axis by reducing serum IGF levels (21) and alter the bile acid pool, which is believed to play an important role in colon carcinogenesis (35). Additionally, Yamaji et al (36) identified that the insulin/insulin-like growth factor-1(IGF) axis acts differently by gender in colorectal carcinogenesis, at least in its early stage. Besides, several studies reported that the association between obesity and CRC risk among women would differ according to the levels of their estrogen status (premenopausal vs. postmenopausal) (15,26,27).…”

A prospective evaluation of C-peptide levels and colorectal adenoma incidence

“…For colorectal adenomas, however, the relationship with C-peptide levels is less certain. The majority of previous studies investigating the circulating C-peptide-colorectal adenoma relationship have been case-control studies, which have usually reported positive relationships [13][14][15]. These studies are vulnerable to reverse causality as serum samples were collected from cases after adenoma diagnosis.…”

“…The relationship between insulin levels or C-peptide levels and colorectal adenoma has rarely Cancer Epidemiology xxx (2015) xxx-xxx been investigated prospectively. Case-control studies have usually reported positive associations between circulating levels of Cpeptide or insulin and colorectal adenomas risk [13][14][15], but the two previous prospective investigations have reported contrasting findings, with one reporting a positive relationship [16] and the other a null result [17].…”