Federal University of Ceará, Department of Pathology and Forensic Medicine, Coronel Nunes de Melo Street, 1315, Rodolfo Teófilo, Fortaleza, Ceará, Brazil.
Harold Juaçaba Diagnostic Center (HHJ) of the Hospital Instituto do Câncer do Ceará (ICC), Papi Júnior Street, 1222, Rodolfo Teófilo, Fortaleza, Ceará, Brazil.
Gene. 2025 Jan 15;933:148977. doi: 10.1016/j.gene.2024.148977. Epub 2024 Oct 9.
Gastric cancer (GC) is the fourth-leading cause of cancer-related mortality. The intestinal subtype of GC comes after the cascade of Correa, presenting H. pylori infection as the major etiological factor. One of the main mechanisms proposed for the progression from a more benign gastric lesion to cancer is DNA damage caused by chronic inflammation. Polymorphisms in DNA repair genes can lead to an imbalance of host DNA damage and repair, contributing to the development of GC. From there, we evaluated the risk of polymorphisms in DNA repair system genes in progressive gastric diseases and their association with the H. pylori genotype. This study included 504 patients from two public hospitals in Brazil's north and northeast regions. The samples were classified into active and inactive gastritis, metaplasia, and GC. Polymorphisms in the DNA repair genes MLH1-93G > A, APE1 2197 T > G, XRCC1 28,152 G > A, MGMT 533 A > G, and XRCC3 18,067C > T were investigated by RFLP-PCR and H. pylori genotype by PCR. Statistical analyses were conducted using EPINFO 7.0., SNPSTAT, and CART software. The XRCC1 (GA) polymorphic allele stood out because it was associated with a lower risk of more severe gastric disease progression. Haplotypes of XRCC1 (GA) associated with some genotypes of MGMT, XRCC3, MLH1, and APE1 also showed protection against the progression of gastric diseases. XRCC3 (CT) showed a decreased risk of gastric disease progression in women, while a risk 1.3x to GC was observed in the MLH1 (A) polymorphic allele. The interaction between H. pylori genes and the host showed that the H. pylori cagE gene was the most important virulence factor associated with a worse clinical outcome, even overlapping with the XRCC1 polymorphism, where the MLH1 polymorphism response varied according to vacA alleles. Our results show the relevance of XRCC1 G > A for genome integrity, sex influence, and interaction between H. pylori virulence factors and XRCC1 and MLH1 genotypes for gastric lesion outcomes in Brazilian populations.
胃癌（GC）是癌症相关死亡的第四大原因。GC 的肠型继 Correa 级联反应之后出现，幽门螺杆菌感染是主要的病因。从更良性的胃部病变发展为癌症的主要机制之一是慢性炎症引起的 DNA 损伤。DNA 修复基因的多态性可导致宿主 DNA 损伤和修复失衡，从而促进 GC 的发生。在此基础上，我们评估了 DNA 修复系统基因多态性在进行性胃部疾病中的风险及其与幽门螺杆菌基因型的关系。本研究纳入了巴西北部和东北部两家公立医院的 504 名患者。样本分为活动性和非活动性胃炎、化生和 GC。通过 RFLP-PCR 检测 MLH1-93G > A、APE1 2197 T > G、XRCC1 28,152 G > A、MGMT 533 A > G 和 XRCC3 18,067C > T 的多态性，通过 PCR 检测幽门螺杆菌基因型。使用 EPINFO 7.0、SNPSTAT 和 CART 软件进行统计分析。XRCC1（GA）多态等位基因引人注目，因为它与更严重的胃部疾病进展风险降低相关。与某些 MGMT、XRCC3、MLH1 和 APE1 基因型相关的 XRCC1（GA）单倍型也显示出对胃部疾病进展的保护作用。XRCC3（CT）在女性中降低了胃部疾病进展的风险，而 MLH1（A）多态性等位基因则使患 GC 的风险增加了 1.3 倍。幽门螺杆菌基因与宿主之间的相互作用表明，幽门螺杆菌 cagE 基因是与较差临床结局相关的最重要毒力因子，甚至与 XRCC1 多态性重叠，其中 MLH1 多态性反应根据 vacA 等位基因而变化。我们的结果表明，XRCC1 G > A 对基因组完整性、性别影响以及 XRCC1 和 MLH1 基因型与幽门螺杆菌毒力因子之间的相互作用具有重要意义，这对巴西人群的胃部病变结局具有重要意义。
