Ma Jing, Giovannucci Edward, Pollak Michael, Leavitt Azita, Tao Yuzhen, Gaziano J Michael, Stampfer Meir J
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Natl Cancer Inst. 2004 Apr 7;96(7):546-53. doi: 10.1093/jnci/djh082.
Colorectal cancer and type 2 diabetes share many risk factors, and hyperinsulinemia appears to be associated with an increased risk of colorectal cancer. We used the concentration of plasma C-peptide (an indicator of insulin production) to determine whether insulin and insulin resistance are associated with the risk of developing colorectal cancer.
We conducted a nested case-control study in the Physicians' Health Study. Plasma samples were collected from 14 916 cancer-free men from August 1982 through December 1984. Plasma C-peptide concentration, measured with an enzyme-linked immunosorbent assay, was available for 176 case patients who developed incident colorectal cancer through December 31, 1995, and 294 age- and smoking status-matched control subjects. Information on four other insulin resistance-related factors at baseline was obtained. We used conditional logistic regression models to investigate associations. All statistical tests were two-sided.
Plasma C-peptide concentration was positively associated with age, body mass index (BMI), and number of insulin resistance-related factors, and it was inversely associated with fasting time before the blood draw, alcohol consumption, and vigorous exercise. An increased concentration of plasma C-peptide was statistically significantly associated with an increased risk of colorectal cancer (relative risk [RR] for the highest versus lowest quintile of plasma C-peptide = 2.7, 95% confidence interval [CI] = 1.2 to 6.2; P(trend) =.047), after adjusting for age, smoking status, fasting, BMI, alcohol consumption, vigorous exercise, and aspirin assignment in the Physicians' Health Study. The association became even stronger when the analysis was further adjusted for factors related to insulin resistance other than insulin levels (RR for the highest versus lowest quintile = 3.4, 95% CI = 1.4 to 8.3; P(trend) =.02) or when data from case patients who were diagnosed during the first 5 years of follow-up were excluded (RR for the highest versus the lowest quintile = 3.4, 95% CI = 1.3 to 8.8; P(trend) =.03). Adjusting for plasma levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) did not materially change the results. There was no apparent modification of risk by BMI, insulin resistance-related factors, or vigorous exercise.
Elevated insulin production, as reflected by elevated concentrations of plasma C-peptide, may predict the risk of developing colorectal cancer, independently of BMI, factors related to insulin resistance, or levels of IGF-I and IGFBP-3.
结直肠癌和2型糖尿病有许多共同的风险因素，高胰岛素血症似乎与结直肠癌风险增加有关。我们利用血浆C肽浓度（胰岛素产生的一个指标）来确定胰岛素和胰岛素抵抗是否与结直肠癌发生风险相关。
我们在医生健康研究中进行了一项巢式病例对照研究。从1982年8月至1984年12月收集了14916名无癌男性的血浆样本。通过酶联免疫吸附测定法测量的血浆C肽浓度，可用于1995年12月31日前发生结直肠癌的176例病例患者以及294名年龄和吸烟状况匹配的对照受试者。获取了基线时其他四个与胰岛素抵抗相关因素的信息。我们使用条件逻辑回归模型来研究相关性。所有统计检验均为双侧检验。
血浆C肽浓度与年龄、体重指数（BMI）以及胰岛素抵抗相关因素的数量呈正相关，与采血前的禁食时间、饮酒量和剧烈运动呈负相关。在对医生健康研究中的年龄、吸烟状况、禁食、BMI、饮酒量、剧烈运动和阿司匹林分配情况进行调整后，血浆C肽浓度升高与结直肠癌风险增加在统计学上显著相关（血浆C肽最高五分位数与最低五分位数的相对风险[RR]=2.7，95%置信区间[CI]=1.2至6.2；P（趋势）=0.047）。当进一步对除胰岛素水平外的与胰岛素抵抗相关因素进行分析调整时（最高五分位数与最低五分位数的RR=3.4，95%CI=1.4至8.3；P（趋势）=0.02），或者排除随访前5年内确诊的病例患者的数据时（最高五分位数与最低五分位数的RR=3.4，95%CI=1.3至8.8；P（趋势）=0.03），这种关联变得更强。对胰岛素样生长因子I（IGF-I）及其结合蛋白3（IGFBP-3）的血浆水平进行调整并没有实质性改变结果。BMI、胰岛素抵抗相关因素或剧烈运动对风险没有明显的修饰作用。
血浆C肽浓度升高所反映的胰岛素产生增加，可能独立于BMI、与胰岛素抵抗相关的因素或IGF-I和IGFBP-3水平，预测结直肠癌发生风险。
