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Biomarkers and Early Detection: Intervention Studies

Effects of isoflavones and lycopene on the insulin-like growth factor (IGF) system in men and women at increased colorectal cancer risk; randomized cross-over trials.

The Netherlands Cancer Institute, Amsterdam, The Netherlands; Wageningen University, Wageningen, The Netherlands; University Medical Center Utrecht, Utrecht, The Netherlands; Fred Hutchinson Cancer Research Center, Seattle, WA; Gelderse Vallei Hospital, Ede, The Netherlands

Abstract

B14

Increased serum insulin-like growth factor (IGF)-I concentrations have been related to increased colorectal cancer risk. Isoflavones and lycopene have both been associated with reduced colorectal cancer risk, and are suggested to interfere with the IGF-system. We investigated the effect of eight weeks supplementation with either isolated isoflavones (84 mg/day) or lycopene (30 mg/day) on serum concentrations of IGF-system components. We conducted randomized, placebo-controlled, double-blinded cross-over trials with an eight-week wash-out period. Our study population consisted of 143 men and postmenopausal women (isoflavone intervention, n=72; lycopene intervention, n=71) with a family history of colorectal cancer or a personal history of colorectal adenomas. Our primary endpoint was the relative difference between serum total IGF-I concentrations after supplementation and after placebo. Secondary endpoints were differences in free IGF-I, total IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3. Isoflavone supplementation in men did not significantly affect any of the IGF-system components. Interestingly, serum total IGF-I was relatively decreased in eight of the nine individuals who were able to convert isoflavones into equol, a more potent estrogenic isoflavone metabolite. For women, outcome measurements are currently being processed. Supplementation with lycopene significantly increased IGFBP-1 (relative difference 30.2%, 95%CI 2.0 - 58.5%) and IGFBP-2 (10.1%, 1.7 - 18.4%) in men and women combined. No significant effects were observed for the other IGF-system components. In conclusion, neither isolated isoflavones nor lycopene lowered serum total IGF-I in our studies. However, subgroup analyses suggest that isoflavones might have an IGF-I lowering effect in equol producers only. Lycopene may confer its effects on the IGF-system indirectly through its binding proteins, as has been previously suggested by experimental studies. Further studies are needed to ascertain the role of isoflavones and lycopene in colorectal cancer prevention.