CONTEXT: Insulin-like growth factor peptides play important roles in regulating cell growth, cell differentiation, and apoptosis, and have been demonstrated to promote the development of colorectal cancer (CRC). OBJECTIVE: To examine the association of insulin-related biomarkers including insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and C-peptide with CRC risk and assess their relevance in predictive models. MATERIALS AND METHODS: The odds ratios of colorectal cancer for serum levels of IGF-1, IGFBP-3 and C-peptide were estimated using unconditional logistic regression models in 100 colorectal cancer cases and 100 control subjects. Areas under the receiving curve (AUC) and integrated discrimination improvement (IDI) statistics were used to assess the discriminatory potential of the models. RESULTS: Serum levels of IGF-1 and IGFBP-3 were negatively associated with colorectal cancer risk (OR=0.07, 95%CI: 0.03-0.16, P for trend <.01, OR=0.06, 95%CI: 0.03-0.15, P for trend <.01 respectively) and serum C-peptide was positively associated with risk of colorectal cancer (OR=4.38, 95%CI: 2.13-9.06, P for trend <.01). Compared to the risk model, prediction for the risk of colorectal cancer had substantially improved when all selected biomarkers IGF-1, IGFBP-3 and inverse value of C-peptide were simultaneously included inthe reference model [P for AUC improvement was 0.02 and the combined IDI reached 0.166% (95 % CI; 0.114-0.219)]. CONCLUSIONS: The results provide evidence for an association of insulin-related biomarkers with colorectal cancer risk and point to consideration as candidate predictor markers.
CONTEXT: Insulin-like growth factor peptides play important roles in regulating cell growth, cell differentiation, and apoptosis, and have been demonstrated to promote the development of colorectal cancer (CRC). OBJECTIVE: To examine the association of insulin-related biomarkers including insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and C-peptide with CRC risk and assess their relevance in predictive models. MATERIALS AND METHODS: The odds ratios of colorectal cancer for serum levels of IGF-1, IGFBP-3 and C-peptide were estimated using unconditional logistic regression models in 100 colorectal cancer cases and 100 control subjects. Areas under the receiving curve (AUC) and integrated discrimination improvement (IDI) statistics were used to assess the discriminatory potential of the models. RESULTS: Serum levels of IGF-1 and IGFBP-3 were negatively associated with colorectal cancer risk (OR=0.07, 95%CI: 0.03-0.16, P for trend <.01, OR=0.06, 95%CI: 0.03-0.15, P for trend <.01 respectively) and serum C-peptide was positively associated with risk of colorectal cancer (OR=4.38, 95%CI: 2.13-9.06, P for trend <.01). Compared to the risk model, prediction for the risk of colorectal cancer had substantially improved when all selected biomarkers IGF-1, IGFBP-3 and inverse value of C-peptide were simultaneously included inthe reference model [P for AUC improvement was 0.02 and the combined IDI reached 0.166% (95 % CI; 0.114-0.219)]. CONCLUSIONS: The results provide evidence for an association of insulin-related biomarkers with colorectal cancer risk and point to consideration as candidate predictor markers.
Authors: Brendan J Guercio; Sui Zhang; Fang-Shu Ou; Alan P Venook; Donna Niedzwiecki; Heinz-Josef Lenz; Federico Innocenti; Michael N Pollak; Andrew B Nixon; Brian C Mullen; Bert H O'Neil; James E Shaw; Blase N Polite; Al Bowen Benson; James N Atkins; Richard M Goldberg; Justin C Brown; Eileen M O'Reilly; Robert J Mayer; Charles D Blanke; Charles S Fuchs; Jeffrey A Meyerhardt Journal: JNCI Cancer Spectr Date: 2020-08-27