Ma J, Giovannucci E, Pollak M, Chan J M, Gaziano J M, Willett W, Stampfer M J
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Natl Cancer Inst. 2001 Sep 5;93(17):1330-6. doi: 10.1093/jnci/93.17.1330.
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.
牛奶和膳食钙可能对结直肠癌具有抗增殖作用，但摄入牛奶也会提高血清胰岛素样生长因子-I（IGF-I）水平。IGF-I与IGF结合蛋白-3（IGFBP-3）的高比值与结直肠癌风险增加有关。
在一项嵌套于医师健康研究中的病例对照研究中，于1982年至1983年期间从14916名年龄在40 - 84岁且回答了饮食问卷的男性中采集血浆样本。在13年随访期间患结直肠癌的193名男性以及318名年龄和吸烟情况相匹配的无癌对照男性中检测IGF-I和IGFBP-3的循环水平。采用条件逻辑回归评估IGF-I/IGFBP-3三分位数和饮食因素与结直肠癌的相对风险（RRs）。统计检验为双侧检验。
总体而言，低脂牛奶或来自乳制品的钙摄入与结直肠癌风险之间存在中度但无统计学意义的负相关。在对照男性中，乳制品（尤其是低脂牛奶）的摄入也与血浆IGF-I、IGFBP-3和IGF-I/IGFBP-3水平呈中度正相关。我们观察到低脂牛奶摄入与IGF-I/IGFBP-3之间在结直肠癌风险方面存在统计学显著的交互作用（P(交互作用)=.03）。IGF-I/IGFBP-3处于最高三分位数的不饮用者比IGF-I/IGFBP-3处于最低三分位数的不饮用者患癌风险高3倍（RR = 3.05；95%置信区间[CI]=1.29至7.24），但在频繁饮用低脂牛奶者中未观察到这种增加（RR = 1.05；95% CI = 0.41至2.69）。相反，在IGF-I/IGFBP-3水平高的男性中，频繁饮用低脂牛奶者的风险比不饮用者低60%（95% CI = 0.17至0.87；P(趋势)=.02）。
乳制品摄入与循环IGF-I水平适度升高有关，但低脂牛奶摄入与结直肠癌风险降低有关，尤其是在IGF-I/IGFBP-3水平高的个体中。这个结直肠癌风险增加的亚组可能从特定饮食干预中获益最大。
