| Colorectal epithelial cell proliferation has been used in many human intervention studies as an intermediate biomarker for colon cancer. Soy isoflavones are phytoestrogens that, based on their biologic activity, may protect against colon cancer. Insulin-like growth factor-I (IGF-I), a circulating hormone and paracrine growth factor, is essential for normal growth in humans, but may be associated with colorectal cancer. IGF-I stimulates proliferation throughout the body, including colonic epithelium.; To test the hypothesis that long-term soy isoflavone supplementation decreases circulating IGF-I concentrations and colon cell proliferation, we conducted a controlled, parallel-arm, double-blinded intervention study with 150 participants (85% men), 50–80 yrs of age. Participants were randomly assigned to consume soy protein daily for 12 months, containing 83 mg isoflavones in the active treatment group (+ISO) and 3 mg isoflavones in the comparison group (−ISO). Colon cell proliferation for the first 91 participants was measured in the cecum, sigmoid colon, and rectum. Mean change in serum IGF-I concentrations was similar in the two groups, indicating no effect of the isoflavone intervention. Soy isoflavone intervention did not reduce cell proliferation or distribution of average height of proliferating cells in any of the three colorectal sites, and, opposite to our hypothesis, increased proliferation count in the sigmoid colon. We conclude that a dietary isoflavone intervention does not reduce colon cell proliferation. We conducted a variance components analysis to isolate sources of variability in Ki-67 measurements of colon cell proliferation. A large proportion of variability was within individuals, indicating a weak measurement signal. Even accounting for multiple measurements per participant, a substantial amount of irreducible within-person variability over time remained. In the cecum, proliferation distribution was higher in older participants. In the sigmoid colon, proliferation count was lower in older participants, and higher in those who reported more exercise. Proliferation distribution in the sigmoid colon was lower in older subjects, and higher in those with higher BMI and energy intake. In the rectum, proliferation distribution count was higher in subjects who reported higher levels of exercise. Overall we found colon cell proliferation and colon cancer to have a limited number of shared risk factors. |
