Circulating insulin-like growth factor binding protein-3 and risk of gastrointestinal malignant tumors.

Abstract

BACKGROUND AND AIM:

Insulin-like growth factor-1 (IGF1) is a potent mitogen and is inhibited by IGF-binding protein-3 (IGFBP3). High serum IGF1 and low IGFBP3 are associated with increased risk of several carcinomas. Here, we assessed the relationship of these peptides with the risk of gastrointestinal malignancies, in a prospective case-control study nested in the Japan Collaborative Cohort Study.

METHODS:

The analysis involved 916 cases who had been diagnosed as gastrointestinal malignancies (C15-25) and 2306 controls. To estimate odds ratios for incidence of malignancies associated with these levels, a conditional logistic model was used.

RESULTS:

Both higher total and free IGFBP3 were associated with a decreased risk of tumor (P for trend < 0.001 and = 0.003, respectively). People in the second to fifth quintiles had lower risk compared to the first quintile (odds ratios ranged 0.532-0.650 and 0.582-0.725, respectively). After adjustment for IGF1, body mass index, drinking, and smoking, total IGFBP3 was inversely correlated with cancer risk (P for trend = 0.031). After adjustment, free IGFBP3 was inversely associated with the risk (P for trend = 0.007). Although total IGF1 was inversely correlated with tumor risk, it was not after controlling for IGFBP3 (P for trend = 0.007 and 0.589, respectively). Free IGF1 was not associated with the risk (P for trend = 0.361). Limiting subjects to those followed for over 3 years reinforced the inverted relationships of total and free IGFBP3 with risk for tumors (P for trend = 0.005 and 0.008, respectively).

CONCLUSION:

Both total and free IGFBP3 may be inversely associated with the incidence of gastrointestinal malignancies.

• Authors: Yasushi Adachi, Masanori Nojima, Mitsuru Mori, Toshiyuki Kubo, Hiro-O Yamano, Yingsong Lin, Kenji Wakai, Akiko Tamakoshi, for JACC Study
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 34 Issue 12 Pg. 2104-2111 (Dec 2019) ISSN: 1440-1746 [Electronic] Australia
• PMID: 31158304 (Publication Type: Journal Article)
• Copyright: © 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• Biomarkers, Tumor
• IGF1 protein, human
• IGFBP3 protein, human
• Insulin-Like Growth Factor Binding Protein 3
• Insulin-Like Growth Factor I

Topics

• Adult
• Aged
• Biomarkers, Tumor (blood)
• Case-Control Studies
• Female
• Follow-Up Studies
• Gastrointestinal Neoplasms (blood, epidemiology)
• Humans
• Incidence
• Insulin-Like Growth Factor Binding Protein 3 (blood)
• Insulin-Like Growth Factor I (metabolism)
• Japan (epidemiology)
• Male
• Middle Aged
• Odds Ratio
• Risk Assessment (methods)
• Risk Factors
• Sex Factors