Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition
Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition
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DOI：
10.1002/ijc.22697
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发表时间：
2007-07-15
影响因子：
6.4
通讯作者：
Kaaks, Rudolf
中科院分区：
文献类型：
--
作者：
Jenab, Mazda;Riboli, Elio;Kaaks, Rudolf
西式饮食和生活方式与肥胖、糖尿病和胰岛素抵抗的发病率增加有关。较高的循环胰岛素水平可以通过增加 IGF-I 的生物活性并降低其一些结合蛋白的生物活性来直接或间接调节细胞增殖和凋亡。本研究的目的是确定血清 C 肽（胰腺胰岛素分泌的生物标志物）以及 IGF 结合蛋白 (IGFBP) -1 和 -2 水平升高与结直肠癌风险之间的关联，该研究属于欧洲癌症与营养前瞻性调查 (EPIC) 的一项病例对照研究，该研究涉及 10 个西欧国家。总共 1,078 例结直肠癌病例（年龄、献血日期、禁食状态、性别、研究中心）与同等数量的对照受试者进行匹配。使用条件逻辑回归模型估计相对癌症风险。最高与最低五分位数相比，血清 C 肽浓度与结直肠癌风险增加呈正相关（OR = 1.56，95% CI = 1.16-2.09，p（趋势）< 0.01），调整 BMI 和体力活动后，该风险略有减弱（OR = 1.37，95% CI = 1.00-1.88，p（趋势）= 0.10）。按解剖部位分层时，结肠（OR 1.67，95% CI = 1.14-2.46，p（趋势）< 0.01）的癌症风险高于直肠（OR 1.42，95% CI = 0.90-2.25，p（趋势）= 0.35）。癌症风险估计因性别或禁食状态而异。没有观察到 IGFBP-1 或 -2 与结直肠癌风险之间存在明确的关联。这项大型前瞻性研究证实，根据 C 肽水平确定的高胰岛素血症与结直肠癌风险增加相关。 (C) 2007 Wiley-Liss, Inc.
Western style diets and lifestyles are associated with increasing rates of obesity, diabetes and insulin resistance. Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF-I and decreasing the bioactivity of some of its binding proteins. The objective of this study was to determine the association of increasing levels of serum C-peptide, a biomarker of pancreatic insulin secretion, and IGF binding proteins (IGFBP) -1 and -2 with colorectal cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 Western European countries. A total of 1,078 colorectal cancer cases were matched (age, date of blood donation, fasting status, gender, study center) to an equal number of control subjects. Relative cancer risks were estimated using conditional logistic regression models. Serum C-peptide concentration was positively associated with an increased colorectal cancer risk for the highest versus the lowest quintile (OR = 1.56, 95% CI = 1.16-2.09, p(trend) < 0.01), which was slightly attenuated after adjustment for BMI and physical activity (OR = 1.37, 95% CI = 1.00-1.88, p(trend) = 0.10). When stratified by anatomical site, the cancer risk was stronger in the colon (OR 1.67, 95% CI = 1.14-2.46, p(trend) < 0.01) than in the rectum (OR 1.42, 95% CI = 0.90-2.25, p(trend) = 0.35). The cancer risk estimates were not heterogeneous by gender or fasting status. No clear colorectal cancer risk associations were observed for IGFBP-1 or -2. This large prospective study confirms that hyperinsulinemia, as determined by C-peptide levels, is associated with an increased colorectal cancer risk. (C) 2007 Wiley-Liss, Inc.