Milk intake, circulating levels of insulin-like growth factor-I, and risk of colorectal cancer in men

Background: Milk and dietary calcium may have antiproliferative effects against colorectal cancer, but milk intake also raises serum levels of insulinlike growth factor-I (IGF-I). A high ratio of IGF-I to IGF-binding protein-3 (IGFBP-3) has been linked to an increased risk of colorectal cancer. Methods: In a case-control study nested in the Physicians' Health Study, plasma samples were collected from the period 1982 through 1983 from 14 916 men, aged 40-84 years, who also answered dietary questionnaires. Circulating levels of IGF-I and IGFBP-3 were assayed among 193 men who developed colorectal cancer during 13 years of follow-up and 318 age- and smoking-matched cancer-free control men. Conditional logistic regression was used to assess relative risks (RRs) of colorectal cancer for tertiles of IGF-I/IGFBP-3 and dietary factors. Statistical tests were two-sided. Results: Overall, there was a moderate but statistically nonsignificant inverse association between intake of low-fat milk or calcium from dairy food and colorectal cancer risk. Intake of dairy food (especially low-fat milk) was also positively and moderately associated with plasma levels of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 among control men. We observed a statistically significant interaction between low-fat milk intake and IGF-I/IGFBP-3 in association with risk of colorectal cancer (P-interaction = .03). Nondrinkers with IGF-I/IGFBP-3 in the highest tertile had a threefold higher risk than nondrinkers with IGF-I/IGFBP-3 in the lowest tertile (RR = 3.05; 95% confidence interval [CI] = 1.29 to 7.24), but no such increase was seen among frequent low-fat milk drinkers (RR = 1.05; 95% CI = 0.41 to 2.69). Conversely, among men with high IGF-I/IGFBP-3, frequent low-fat milk drinkers had a 60% lower risk (95% CI = 0.17 to 0.87; P-trend = .02) than nondrinkers. Conclusion: Intake of dairy products was associated with a modest increase in circulating IGF-I levels, but intake of low-fat milk was associated with lower risk of colorectal cancer, particularly among individuals with high IGF-I/IGFBP-3. This subpopulation, which is at increased risk of colorectal cancer, might benefit the most from specific dietary intervention.