title: 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)<0.001 and 0.02, respectively) and an inverse association of IGFBP-1 (P (trend)=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)=0.03) and marginally significant for IGF-I and IGFBP-1 (P (interaction)=0.14 and 0.12, respectively).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan. tyamaji@ ncc.go.jp
authors.forename: T
authors.initials: T
authors.lastname: Yamaji
authors.forename: M
authors.initials: M
authors.lastname: Iwasaki
authors.forename: S
authors.initials: S
authors.lastname: Sasazuki
authors.forename: S
authors.initials: S
authors.lastname: Tsugane
mesh_terms: D000236:Adenoma / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D000328:Adult; D000368:Aged; D044466:Asian People; D002096:C-Peptide / Q000097:blood*; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D003113:Colonoscopy / Q000706:statistics & numerical data; D015179:Colorectal Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008019:Life Style; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D016017:Odds Ratio; D012307:Risk Factors; D017678:Sex Distribution; D012737:Sex Factors; D011795:Surveys and Questionnaires
chemical_list: D002096:C-Peptide; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I