Division of Cancer Epidemiology and Genetics, NCI, Rockville, Maryland.
Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
Cancer Epidemiol Biomarkers Prev. 2019 Apr;28(4):829-832. doi: 10.1158/1055-9965.EPI-18-1157. Epub 2019 Mar 15.
Circulating inflammation proteins may be important mediators or markers of carcinogenic mechanisms. There have been few studies with limited numbers of analytes in patients with upper gastrointestinal (GI) tract tumors. We therefore evaluated risk associations of gastric and esophageal cancers with prediagnostic levels of a wide range of these molecules.
We performed a case-cohort analysis within the Japan Public Health Center-Based Prospective Study Cohort II, including incident cases of gastric ( = 446) and esophageal ( = 68) cancers and a random subcohort ( = 774). A total of 64 biomarkers were measured in baseline plasma using Luminex bead-based assays. The median time between blood collection and diagnosis was 8.1 years for gastric cancer and 9.4 years for esophageal cancer. HRs for association with each marker were adjusted for potential confounders using Cox regression.
In separate models, sEGFR and TSLP were nominally associated with gastric cancer risk, and CRP, CXCL11/ITAC, and CCL15/MIP1D were associated with esophageal cancer. However, no association satisfied statistical significance after FDR correction. Associations did not differ by time from blood collection to cancer (<5 vs. ≥5 years).
Our study failed to identify associations of circulating inflammation markers with risk of upper GI tract tumors.
To date, this is the largest assessment of inflammation-related proteins with gastric and esophageal cancer risks. However, the evaluated molecules may not fully represent the complex inflammation processes preceding malignant transformation. Further investigation of other markers in prospective studies is warranted, as demonstration of associations may have important implications for prevention and treatment of these cancers.
循环炎症蛋白可能是致癌机制的重要介质或标志物。针对上消化道（GI）肿瘤患者的此类分析物数量有限的研究较少。因此，我们评估了广泛的此类分子在预测胃和食管癌风险中的作用。
我们在日本公共卫生中心前瞻性研究 II 队列中进行了病例 - 队列分析，包括胃（=446）和食管（=68）癌症的病例和随机亚队列（=774）。使用 Luminex 珠基检测法在基线血浆中测量了 64 种生物标志物。从采血到诊断的中位时间为胃癌 8.1 年，食管癌 9.4 年。使用 Cox 回归调整潜在混杂因素后，每个标志物的 HR 与关联。
在单独的模型中，sEGFR 和 TSLP 与胃癌风险呈名义相关，而 CRP、CXCL11/ITAC 和 CCL15/MIP1D 与食管癌相关。然而，在 FDR 校正后，没有关联具有统计学意义。关联在采血到癌症的时间上没有差异（<5 年与≥5 年）。
我们的研究未能确定循环炎症标志物与上消化道肿瘤风险之间的关联。
迄今为止，这是最大规模的与胃癌和食管癌风险相关的炎症相关蛋白评估。然而，评估的分子可能无法完全代表恶性转化前复杂的炎症过程。需要在前瞻性研究中进一步研究其他标志物，因为证明关联可能对这些癌症的预防和治疗具有重要意义。
