Hang Dong, He Xiaosheng, Kværner Ane Sørlie, Chan Andrew T, Wu Kana, Ogino Shuji, Hu Zhibin, Shen Hongbing, Pollak Michael N, Giovannucci Edward L, Song Mingyang
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
JNCI Cancer Spectr. 2019 Aug 1;3(3):pkz056. doi: 10.1093/jncics/pkz056. eCollection 2019 Sep.
Hyperinsulinemia, high insulin-like growth factor 1 (IGF1) levels, and low IGF binding protein 1 (IGFBP1) levels have been implicated in the relationship between obesity and increased risk of colorectal cancer (CRC). However, it remains inconclusive whether circulating biomarkers of insulin and the IGF axis are associated with conventional adenoma and serrated polyp, the two distinct groups of CRC precursors.
We prospectively examined the associations of plasma C-peptide, IGF1, IGFBP1, IGFBP3, and IGF1 to IGFBP3 ratio with conventional adenoma and serrated polyp among 11 072 women from the Nurses' Health Studies. Multivariable logistic regression was used to calculate the odds ratio (OR) per 1-SD increase in each biomarker for overall risk of conventional adenoma and serrated polyp and according to polyp feature.
During 20 years of follow-up, we documented 1234 conventional adenomas and 914 serrated polyps. After adjusting for various lifestyle factors (including body mass index), higher concentrations of IGFBP1 were associated with lower risk of serrated polyp (OR = 0.84, 95% confidence interval = 0.75 to 0.95, =.005). The association was particularly strong for large serrated polyp (≥10 mm) located in the distal colon and rectum (OR = 0.59, 95% confidence interval = 0.39 to 0.87, =.01). In contrast, we did not find any statistically significant association between the biomarkers and conventional adenoma.
A higher plasma level of IGFBP1 was associated with lower risk of serrated polyp. Our findings support a potential role of IGFBP1 in the serrated pathway of CRC in women.
高胰岛素血症、高胰岛素样生长因子1（IGF1）水平以及低胰岛素样生长因子结合蛋白1（IGFBP1）水平与肥胖及结直肠癌（CRC）风险增加之间的关系已得到证实。然而，胰岛素和IGF轴的循环生物标志物是否与传统腺瘤和锯齿状息肉（CRC的两种不同前体类型）相关仍无定论。
我们前瞻性地研究了护士健康研究中11072名女性的血浆C肽、IGF1、IGFBP1、IGFBP3以及IGF1与IGFBP3比值和传统腺瘤及锯齿状息肉之间的关联。采用多变量逻辑回归计算每种生物标志物每增加1个标准差时传统腺瘤和锯齿状息肉总体风险以及根据息肉特征的比值比（OR）。
在20年的随访期间，我们记录了1234例传统腺瘤和914例锯齿状息肉。在调整了各种生活方式因素（包括体重指数）后，较高的IGFBP1浓度与较低的锯齿状息肉风险相关（OR = 0.84，95%置信区间 = 0.75至0.95，P = 0.005）。对于位于结肠远端和直肠的大锯齿状息肉（≥10毫米），这种关联尤为强烈（OR = 0.59，95%置信区间 = 0.39至0.87，P = 0.01）。相比之下，我们未发现这些生物标志物与传统腺瘤之间存在任何具有统计学意义的关联。
较高的血浆IGFBP1水平与较低的锯齿状息肉风险相关。我们的研究结果支持IGFBP1在女性CRC锯齿状途径中的潜在作用。
