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First page of Associations between serum insulin-like growth factor-related molecules and colorectal cancer risk by tumor location: a nested case-control study

Introduction, The activity of the mitogen insulin-like growth factor (IGF) is controlled by IGF-binding protein (IGFBP). Colorectal cancers (CRCs) are heterogeneous, with left- and right-sided CRC showing different clinical and molecular characteristics. This case-control study, nested in the Japan Collaborative Cohort study, assessed associations between serum levels of IGF-related molecules and incidences of CRC by location. Methods, A baseline survey obtained serum samples from 39,242 participants. Subjects diagnosed with CRC during follow-up were regarded as cases. Conditional logistic regression modeling was used to calculate odds ratios (ORs) for cancer incidence associated with IGF-related molecules. Results, This analysis included 176 cases and 524 controls. No IGF-related molecules appeared associated with risks of overall or left-sided CRC. Both total IGFBP3 and free IGFBP3 (estimated as IGFBP3-(IGF1+IGF2)) were associated with incidence of right-sided CRC (P-for-trends=0.027 and 0.003, respectively), with the third tertile of total and free IGFBP3 showing the highest risk (OR=6.25 and 7.96, respectively). Free IGF, estimated as (IGF1+IGF2)/IGFBP3, was inversely associated with incidence of right-sided CRC (P-for-trends=0.014), with the third tertile showing the lowest risk (OR=0.18). Among subjects followed for over 3 years, association of IGF-related molecules with overall CRC was similar. Free IGFBP3 was associated with incidence of right-sided CRC (P-for-trends=0.004). Free IGF was inversely associated with incidence of right-sided CRC (P-for-trends=0.002). However, free IGFs were associated with risk of left-sided CRC (P-for-trends=0.041), with the third tertile showing the highest risk (OR=3.10). Conclusions, Serum IGF-related molecules are associated with risk of CRC. These associations might differ by tumor location.

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S. Karger AG, Basel
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2025
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