Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, México City, Mexico.
J Gastroenterol Hepatol. 2019 May;34(5):852-856. doi: 10.1111/jgh.14518. Epub 2018 Nov 18.
Chronic Helicobacter pylori infection causes gastric mucosal inflammation as an important antecedent of gastric cancer. We aimed to evaluate associations of blood markers of inflammation with gastric intestinal metaplasia and dysplasia in H. pylori-infected individuals.
We compared pre-treatment serum levels of immune-related and inflammation-related markers between 99 individuals with intestinal metaplasia or dysplasia and 75 control individuals with non-atrophic gastritis within an H. pylori eradication trial in Mexico. Serum levels of 28 markers measured with Luminex bead-based assays were categorized in tertiles as low (T1), middle (T2), and high (T3). Logistic regression models were used to calculate age-adjusted and sex-adjusted odds ratios and 95% confidence intervals. All statistical tests were two-sided, and significance values were adjusted for multiple comparisons using false discovery rate methods.
Five markers were nominally associated (P < 0.05) with the presence of advanced premalignant gastric lesions. Adjusted odds ratios (95% confidence interval) of T2 and T3 versus T1 were 4.09 (1.65-10.17) and 3.08 (1.23-7.68) for CCL3/MIP1A, 3.21 (1.33-7.75) and 2.69 (1.10-6.57) for CCL20/MIP3A levels, 1.79 (0.77-4.18) and 2.39 (1.02-5.60) for IL-1β, 1.34 (0.56-3.19) and 3.02 (1.29-7.12) for IL-4, and 1.07 (0.44-2.59) and 3.07 (1.32-7.14) for IL-5, respectively. Two (IL-4 and IL-5) of the five markers had false discovery rate adjusted P < 0.2.
Our results suggest that certain Th2 and other cytokines may have a role in promoting carcinogenesis in the setting of H. pylori infection. Additional research is needed to replicate these findings, extend to pre-diagnostic samples, and elucidate the underlying mechanisms.
慢性幽门螺杆菌感染会引起胃黏膜炎症，这是胃癌的重要前驱病变。本研究旨在评估炎症血液标志物与幽门螺杆菌感染者胃肠化生和异型增生之间的关系。
我们比较了墨西哥一项幽门螺杆菌根除试验中 99 例肠化生或异型增生患者和 75 例非萎缩性胃炎患者的治疗前血清中免疫相关和炎症相关标志物的水平。采用基于 Luminex 珠的检测方法测定 28 种标志物的血清水平，并分为低 (T1)、中 (T2) 和高 (T3) 三个三分位组。采用 logistic 回归模型计算年龄和性别校正后的比值比和 95%置信区间。所有统计检验均为双侧检验，使用错误发现率方法对多重比较进行校正。
有 5 种标志物与进展期癌前胃病变的存在呈名义相关 (P < 0.05)。与 T1 相比，T2 和 T3 的调整比值比 (95%置信区间) 分别为 CCL3/MIP1A 的 4.09 (1.65-10.17) 和 3.08 (1.23-7.68)、CCL20/MIP3A 水平的 3.21 (1.33-7.75) 和 2.69 (1.10-6.57)、IL-1β 的 1.79 (0.77-4.18) 和 2.39 (1.02-5.60)、IL-4 的 1.34 (0.56-3.19) 和 3.02 (1.29-7.12)、IL-5 的 1.07 (0.44-2.59) 和 3.07 (1.32-7.14)。在这 5 种标志物中，有 2 种（IL-4 和 IL-5）的错误发现率校正后 P < 0.2。
我们的结果表明，某些 Th2 细胞和其他细胞因子可能在幽门螺杆菌感染的情况下在促进癌变中发挥作用。需要进一步的研究来复制这些发现，扩展到诊断前样本，并阐明潜在的机制。
