Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
HPV Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Carcinogenesis. 2019 Jul 6;40(6):765-770. doi: 10.1093/carcin/bgz027.
Inflammation is a driver of colorectal neoplasia; however, what particular inflammatory processes play a role in early carcinogenesis are unclear. We compared serum levels of 78 inflammation markers between 171 pathologically confirmed colorectal adenoma cases (including 48 incident cases) and 344 controls within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used weighted multivariable logistic regression to compute odds ratio (OR) and 95% confidence interval (CI). We found 14 markers associated with risk of adenoma overall; three of these were also associated with incident adenoma: CC-chemokine cysteine motif chemokine ligand 20 (CCL20) [overall adenoma fourth versus first quartile: OR 4.8, 95% CI 2.0-12, Ptrend 0.0007; incident adenoma third versus first tertile: OR 4.6, 95% CI 1.0-22, Ptrend 0.03], growth-related gene oncogene products (GRO) [OR 3.8, 95% CI 1.6-9.3, Ptrend 0.006 and OR 3.6, 95% CI 1.1-12, Ptrend 0.04, respectively] and insulin [OR 2.9, 95% CI 0.8-10, Ptrend 0.05 and OR 7.8, 95% CI 1.3-46, Ptrend 0.03, respectively]. All statistical tests were two-sided. These results provide important new evidence implicating CCL20- and GRO-related pathways in early colorectal carcinogenesis and further support a role for insulin.
炎症是结直肠肿瘤发生的驱动因素;然而,哪些特定的炎症过程在早期癌变中起作用尚不清楚。我们比较了 171 例经病理证实的结直肠腺瘤病例(包括 48 例新发病例)和前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验中的 344 例对照者的血清 78 种炎症标志物水平。我们使用加权多变量逻辑回归计算比值比(OR)和 95%置信区间(CI)。我们发现了 14 个与腺瘤总体风险相关的标志物;其中有三个标志物也与新发病例腺瘤相关:CC-趋化因子半胱氨酸基序趋化因子配体 20(CCL20)[总体腺瘤第四与第一四分位数:OR 4.8,95%CI 2.0-12,Ptrend 0.0007;新发病例腺瘤第三与第一三分位数:OR 4.6,95%CI 1.0-22,Ptrend 0.03],生长相关基因癌基因产物(GRO)[OR 3.8,95%CI 1.6-9.3,Ptrend 0.006 和 OR 3.6,95%CI 1.1-12,Ptrend 0.04]和胰岛素[OR 2.9,95%CI 0.8-10,Ptrend 0.05 和 OR 7.8,95%CI 1.3-46,Ptrend 0.03]。所有的统计检验都是双侧的。这些结果为 CCL20 和 GRO 相关途径在结直肠早期癌变中的作用提供了重要的新证据,并进一步支持了胰岛素的作用。