Insulin-like Growth Factor-1, Insulin-like Growth Factor Binding Protein-3 and the Incidence of Malignant Neoplasms in a Nested Case?Control Study
Insulin-like Growth Factor-1, Insulin-like Growth Factor Binding Protein-3 and the Incidence of Malignant Neoplasms in a Nested Case?Control Study
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胰岛素样生长因子-1、胰岛素样生长因子结合蛋白-3与嵌套病例中恶性肿瘤发病率对照研究
DOI：
10.1158/1940-6207.capr-19-0375
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发表时间：
2020
影响因子：
3.3
通讯作者：
Tamakoshi Akiko
中科院分区：
文献类型：
--
作者：
Adachi Yasushi;Nojima Masanori;Mori Mitsuru;Himori Ryogo;Kubo Toshiyuki;Yamano Hiro-o.;Lin Yingsong;Wakai Kenji;Tamakoshi Akiko
胰岛素样生长因子(IGF)-1是一种强有力的有丝分裂原，但IGF结合蛋白(IGFBP)-3抑制IGF1。为了阐明IGF1和IGFBP两者与肿瘤发生风险的关系，在日本合作队列研究中嵌套的前瞻性病例对照研究中，研究了IGF1和IGFBP3血清水平与恶性肿瘤发病率的关系。1988年至1990年开始了一项基线调查，共有110,585名受试者参加，35%的参与者捐献了血液样本。那些在1997年之前被诊断出患有恶性肿瘤的人被认为是病例。分析涉及1,349例病例和4,012名对照。条件Logistic回归用于估计与IGF相关分子相关的癌症发病率的OR。在控制了酒精摄入量、体重指数和吸烟后，高总IGFBP3和高游离IGFBP3的参与者(通过IGFBP3IGF1的摩尔差值估计)有患未来肿瘤的风险(−分别为0.014和0.009)，但IGF1的参与者没有。第二到第五个五分之一的人比第一个五分之一的人风险更低(OR值分别为0.676-0.736和0.657-0.870)。将受试者限制在随访3年的时间内，减弱了总IGFBP3和游离IGFBP3的负相关性，而由IGF1/IGFBP3的摩尔比估计的游离IGF1呈正相关(P趋势分别为0.004、0.002和0.013)。在控制了酒精摄入量、吸烟、体重指数和糖尿病后，结果得到了证实。这些发现表明，血清IGF1和IGFBP3与未来患恶性肿瘤的风险有关。
Insulin-like growth factor (IGF)-1 is a potent mitogen, but IGF binding protein (IGFBP)-3 inhibits IGF1. To elucidate the relationship between both IGF1 and IGFBP and the risk of tumorigenesis, the association between IGF1 and IGFBP3 serum levels and of malignant tumor incidence was investigated in a prospective case–control study nested in the Japan Collaborative Cohort Study. A baseline survey was started in 1988–1990, 110,585 subjects were enrolled, and 35% of participants donated blood samples. Those who had been diagnosed with malignant tumors by 1997 were considered cases. The analysis involved 1,349 cases and 4,012 controls. Conditional logistic regression was used to estimate ORs for cancer incidence associated with IGF-related molecules. After controlling for alcohol intake, body mass index (BMI), and smoking, participants with high total-IGFBP3 and free-IGFBP3, which is estimated by the molar difference of (IGFBP3 − IGF1), had a risk of future neoplasms (Ptrend= 0.014 and 0.009, respectively), but those with IGF1 did not. People in the second to fifth quintiles had a lower risk than those in the first quintile (ORs 0.676–0.736 and 0.657–0.870, respectively). Limiting subjects to those followed for 3 years weakened the negative associations of total- and free-IGFBP3, whereas a positive relationship of free-IGF1, which was estimated by the molar ratio of IGF1/IGFBP3, was seen (Ptrend= 0.004, 0.002, and 0.013, respectively). After controlling for alcohol intake, smoking, BMI, and diabetes mellitus, the results were confirmed. These findings suggest that serum IGF1 and IGFBP3 are related to future risk of malignant neoplasms.