Wei Esther K, Ma Jing, Pollak Michael N, Rifai Nader, Fuchs Charles S, Hankinson Susan E, Giovannucci Edward
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):750-5. doi: 10.1158/1055-9965.EPI-05-0820.
Determinants of insulin secretion and insulin-like growth factors (IGF) have been directly associated with risk for colorectal cancer. However, few studies have evaluated whether these factors are also associated with risk of colorectal adenoma, the main precursor lesion to colorectal cancer.
We identified 380 distal colorectal adenoma cases diagnosed between 1989 and 1998 and 380 controls among nondiabetic women from the cohort of 32,826 women, nested in the Nurses' Health Study, who provided blood samples in 1989 to 1990. Cases and controls were individually matched on year of birth, time period of and indication(s) for endoscopy, and date of blood draw.
High concentrations of C-peptide, an indicator of insulin secretion, were statistically significantly associated with risk of distal colorectal adenoma [multivariable relative risk (MVRR) top versus bottom quartile, 1.63; 95% confidence interval (95% CI), 1.01-2.66; P = 0.01], even after including body mass index and physical activity in the statistical model. Fasting IGF binding protein-1 (IGFBP-1) concentrations did not show any clear association with risk for adenoma (MVRR top versus bottom quartile, 1.08; 95% CI, 0.56-2.07). These associations did not differ significantly by size/stage of adenoma. Glycosylated hemoglobin (HbA1c) was associated with a nonstatistically significant increased risk of colorectal adenoma (MVRR top versus bottom quartile, 1.47; 95% CI, 0.89-2.44).
High HbA1c and low IGFBP-1 were not clearly associated with increased risk of distal colorectal adenoma. However, our current results and previous associations between C-peptide and colorectal cancer suggest that hyperinsulinemia may play a role throughout the development of colorectal neoplasia.
胰岛素分泌的决定因素和胰岛素样生长因子（IGF）与结直肠癌风险直接相关。然而，很少有研究评估这些因素是否也与结直肠癌的主要前驱病变——结直肠腺瘤的风险相关。
我们从护士健康研究队列中的32826名女性中，确定了1989年至1998年间诊断出的380例远端结直肠腺瘤病例和380名对照，这些女性在1989年至1990年期间提供了血液样本。病例和对照根据出生年份、内镜检查的时间段和指征以及采血日期进行个体匹配。
即使在统计模型中纳入体重指数和身体活动后，胰岛素分泌指标C肽的高浓度与远端结直肠腺瘤风险在统计学上仍显著相关[多变量相对风险（MVRR）最高四分位数与最低四分位数相比，为1.63；95%置信区间（95%CI），1.01 - 2.66；P = 0.01]。空腹IGF结合蛋白-1（IGFBP-1）浓度与腺瘤风险未显示出任何明确关联（MVRR最高四分位数与最低四分位数相比，为1.08；95%CI，0.56 - 2.07）。这些关联在腺瘤的大小/分期方面无显著差异。糖化血红蛋白（HbA1c）与结直肠腺瘤风险的增加无统计学显著关联（MVRR最高四分位数与最低四分位数相比，为1.47；95%CI，0.89 - 2.44）。
高HbA1c和低IGFBP-1与远端结直肠腺瘤风险增加无明确关联。然而，我们目前的结果以及先前C肽与结直肠癌之间的关联表明，高胰岛素血症可能在结直肠肿瘤形成的整个过程中起作用。
