Association of Serum Retinol and Carotenoids with Insulin-like Growth Factors and Insulin-like Growth Factor Binding Protein-3 among Control Subjects of a Nested Case-control Study in the JACC Study

Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival,and thus are thought to be important for tumor development. Carotenoids and retinol have been linked to theprevention of several cancers. We here evaluated associations of serum levels of carotenoids and retinol withIGF-I, IGF-II, and IGFBP-3 within the context of the JACC Study. The study subjects were 924 controls (578men and 346 women) of a nested case-control study of lung and colorectal cancer risk . Using frozen-stored sera,serum levels of α-carotene, β-carotene, lycopene, β-cryptoxanthin, zeaxanthin/lutein, and retinol were separatelydetermined using high-performance liquid chromatography. Serum levels of IGF-I, IGF-II, and IGFBP-3 weremeasured by immuno-radiometric assay. Confounding factors-adjusted least squares mean levels of serum IGFI,IGF-II, and IGFBP-3 for each quartile of serum levels of carotenoids and retinol were estimated. Serum IGFI,IGF-II, and IGFBP-3 levels increased with increasing serum retinol levels. Moreover, serum IGF-I levels weresignificantly higher in highest quartile of serum provitamin A, such as α-carotene, β-carotene, and β-cryptoxanthin, among women. Serum IGFBP-3 levels decreased with increasing serum lycopene levels in womenand with increasing serum zeaxanthin/lutein levels in men. The current study indicates that positive associationsexist for serum retinol levels with serum levels of IGF-I, IGF-II, and IGFBP-3 independent of age, BMI, smokinghabits, drinking habits, and intake of energy and protein among Japanese healthy men and women.