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J Natl Cancer Inst. 2001 Sep 5;93(17):1330-6.

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

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Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.



Milk and dietary calcium may have antiproliferative effects against colorectal cancer, but milk intake also raises serum levels of insulin-like 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.


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.


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.


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.

[Indexed for MEDLINE]

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