幽门螺杆菌感染的慢性胃炎、肠型胃癌和家族性胃癌患者的突变。
Mutations in Helicobacter pylori infected patients with chronic gastritis, intestinal type of gastric cancer and familial gastric cancer.
作者信息
Hnatyszyn Andrzej, Szalata Marlena, Zielińska Aleksandra, Wielgus Karolina, Danielewski Mikołaj, Hnatyszyn Piotr Tomasz, Pławski Andrzej, Walkowiak Jarosław, Słomski Ryszard
机构信息
Independent Public Health Care Centre in Nowa Sol, Multispecialty Hospital, Chalubinskiego 7, Nowa Sol, 67-100, Poland.
Department of Biochemistry and Biotechnology, Poznań University of Life Sciences, Dojazd 11, Poznań, 60-632, Poland.
出版信息
Hered Cancer Clin Pract. 2024 Jun 12;22(1):9. doi: 10.1186/s13053-024-00282-8.
BACKGROUND
Development of sequential changes of mucous leading to gastric cancer and familial cases of gastric cancer of intestinal type is widely connected with Helicobacter pylori infections. In this study we analysed variants of genes involved in cancerogenesis and inflammatory processes of intestines in patients infected with H.pylori. Our goal was to test whether mutations in these genes predestinate to development of gastric cancer, and whether there is a genetic factor that makes it more likely for infections with H.pylori to cause gastric cancer. As infections with H. pylori are relatively common, discovering such genetic predispositions could be used for establishing risk-groups and for planning treatments.
METHODS
Our studies cover analysis of variants in genes involved in cancerogenesis: TP53 (rs11540652, rs587782329, COSM10771), MSH2 (rs193922376), MLH1 (rs63750217), and inflammatory processes of intestine: NOD2 (rs2066847, rs2066842), IL1A (rs1800587) and IL1B (rs1143634) from H.pylori-infected patients.
RESULTS
Mutations were more common in the group of patients with gastric cancer of intestinal type and familial cases of gastric cancer in comparison with patients with chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer (p-value = 0.00824), with the prevalence of p53 mutations in patients with familial gastric cancer vs. patients with other changes of mucosa (p-value = 0.000049). Additionally, gastric cancer patients have mainly genotype TT or CT of the rs2066842 variant of the NOD2 gene.
CONCLUSIONS
The lack of statistically significant changes of other interleukin genes involved in inflammatory processes may suggest the presence of H.pylori infection as a potential trigger for the development of the inflammatory process of the mucosa, leading through microbiota dysbiosis to the development of enteric gastric cancer. Mutations in analysed genes correlated with more severe mucosal changes, with a much more frequent presence of TP53 gene mutations, with a limited presence of other mutations in the familial history of gastric cancer.
背景
导致胃癌及家族性肠型胃癌的黏液序贯性变化的发展与幽门螺杆菌感染密切相关。在本研究中，我们分析了幽门螺杆菌感染患者中参与肠道癌变和炎症过程的基因变体。我们的目标是测试这些基因中的突变是否预示着胃癌的发生，以及是否存在一种遗传因素使幽门螺杆菌感染更易引发胃癌。由于幽门螺杆菌感染相对常见，发现此类遗传易感性可用于确定风险群体和规划治疗方案。
方法
我们的研究涵盖了对参与癌变的基因变体的分析：TP53（rs11540652、rs587782329、COSM10771）、MSH2（rs193922376）、MLH1（rs63750217），以及参与肠道炎症过程的基因变体：NOD2（rs2066847、rs2066842）、IL1A（rs1800587）和IL1B（rs1143634），这些基因来自幽门螺杆菌感染患者。
结果
与慢性胃炎、慢性萎缩性胃炎、肠化生、发育异常或胃癌患者相比，肠型胃癌患者组和家族性胃癌患者组中的突变更为常见（p值 = 0.00824），家族性胃癌患者中p53突变的患病率与其他黏膜变化患者相比（p值 = 0.000049）。此外，胃癌患者主要具有NOD2基因rs2066842变体的TT或CT基因型。
结论
参与炎症过程的其他白细胞介素基因缺乏具有统计学意义的变化，这可能表明幽门螺杆菌感染是黏膜炎症过程发展的潜在触发因素，通过微生物群失调导致肠型胃癌的发生。分析基因中的突变与更严重的黏膜变化相关，TP53基因突变更为频繁，而在胃癌家族史中其他突变的存在有限。
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