Serum IGFs--Effects of a Soy Intervention in Humans

Fred Hutchinson Cancer Research Center, Seattle WA

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Abstract

DESCRIPTION (provided by applicant): Insulin-like growth factors (IGFs) regulate cell proliferation in the body. IGF-I circulates in blood and acts to promote growth in tissues. Its carrier protein, IGFBP-3, binds IGF-I in circulation. This reduces IGF-I activity, but also increases its half-life in blood. In observational studies, high serum IGF-I, low serum IGFBP-3, or a high molar ratio of IGF-I relative to IGFBP-3 are associated with increased risk of breast, prostate, lung, and colon cancers, as well as larger colon polyps. This suggests that it may be beneficial to modify levels of circulating IGFs. Intervention studies in humans have shown that it is possible to alter levels of circulating IGFs; several classes of drugs and calorie or protein restriction all decrease serum IGF-I, increase IGFBP3, or both. Studies in animals and one report in humans suggest that isoflavones, bioactive agents in soybeans, can also alter IGF levels in directions that may protect against cancer. Our specific aim is to determine whether a 12-month soy isoflavone intervention alters serum IGF-I and IGFBP-3. Secondly, we seek to determine whether serum IGF concentrations are associated with colonic epithelial cell proliferation indices in individuals with adenomatous polyps. We propose to measure IGFs in serum that has been collected from 140 participants in the Soy Isoflavone Prevention Study (SIP; NC1 U0l CA7203501). SIP is a double-blinded, randomized, controlled trial in men and women, ages 50-80 years, with adenomatous polyps. SIP is a two-arm intervention. Participants consume a soy beverage that either contains isoflavones (intervention) or has had isoflavones removed (control). SIP is collecting and storing serum samples at 0,4, 8, and 12 months and colon biopsies at 0 and 12 months. We will measure serum IGF-I and IGFBP-3 in samples collected from the 4 time points, examine the effect of isoflavone intervention on IGF concentrations, and determine the relationship between IGFs and colon cell proliferation (Ki67-labeling). We will use data on cell proliferation and serum isoflavone concentrations from the SIP study. Thus, our proposed study makes efficient use of stored serum and other materials and data from the existing intervention. To date, SIP is the largest soy-isoflavone intervention in a study population at increased risk of colon cancer. It provides an ideal design to evaluate the effects of isoflavones on the IGF system and to explore relationships between IGFs and colonic epithelial cell proliferation in humans.