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Published on: March 14, 2019
Associations between Serum Insulin-Like Growth Factor-Related Molecules and Colorectal Cancer Risk by Tumor Location:
Yasushi Adachi, Masanori Nojima1,2, Yingsong Lin3
1Division of Gastroenterology, Department of Internal Medicine, Sapporo Shirakaba-dai Hospital, Sapporo, Japan.
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 CRCs, 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, the association of IGF-related molecules with overall CRC was similar. Free IGFBP3 was associated with the incidence of right-sided CRC (p for trends = 0.004). Free IGF was inversely associated with the incidence of right-sided CRC (p for trends = 0.002). However, free IGFs were associated with a 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 the risk of CRC. These associations might differ by tumor location.
