研究动态Dynamic

当前位置:首页 > 研究动态

Carcinogenesis文章:幽门螺旋菌相关的宿主基因多态性与中国人胃癌易感性的关联研究

幽门螺杆菌(Hp)感染被认为是胃癌的重要危险因素,而基因多态性决定个体之间存在着差异,基因多态性对胃癌发病的作用近年来逐渐引起重视。胃癌的发生经历从正常粘膜/浅表性胃炎,萎缩性胃炎(atrophic gastritis,GA)到胃癌(gastric cancer,GC)的过程。单独的宿主因素或联合幽门螺旋杆菌感染可能会影响胃癌发生进程。中国医科大学附属第一医院的研究者针对6个幽门螺旋菌相关的宿主基因(MUC1,TLR4,PTPN11,IL-1B,PGC,PGA3–5)的24个标签SNP(tagSNP,对包含254例GA,236例GC和552例对照采用高通量Sequenom SNP检测。根据筛选结果进一步扩大研究样本对包含907例GA,714例GC和1276例对照的群体中进行5个标签SNP(位于TLR4, PGC和PTPN11基因)进行分型。对SNP分型数据进行疾病关联分析发现PGC rs6458238, PGC rs4711690和PTPN11 rs12229892与GA和/或GC发病相关。并且, rs4711690和rs12229892与幽门螺旋菌在GA发病风险中存在显著相互作用。对胃癌样本检测发现rs6458238的GA杂合型个体的PGC基因mRNA表达量显著高于更常见的GG纯合型个体。这些发现预示幽门螺旋菌感染相关的两个关键宿主基因PGC(参与粘膜防御)和PTPN11(参与细胞信号)可以独立或与幽门螺旋菌互作,影响GC和GA发病风险和癌变进程。这些发现有待进一步的功能实验和独立大样本群体研究的进一步证实。该研究已经发表在2013年Carcinogenesis杂志上。本研究中Sequenom SNP分型检测工作由博奥生物集团有限公司完成。


原文摘要:
Helicobacter pylori-related host gene polymorphisms associated with susceptibility of gastric carcinogenesis: a two-stage case-control study in Chinese
Stomach carcinogenesis progresses stepwise from normal mucosa/superficial gastritis, atrophic gastritis (GA) to gastric cancer (GC). Host factors independent of or combined with Helicobacter pylori infection may modulate the carcinogenesis process. In this two-stage study, we selected 24 putative functional tag single-nucleotide polymorphisms (tagSNPs) for six H.pylori-related host genes, MUC1, toll-like receptor 4 (TLR4), protein tyrosine phosphatase, non-receptor type 11 (PTPN11), IL-1B, PGC and PGA3–5, and analyzed their influence and interaction with H.pylori on the GA and GC risks. Using high-throughput genotyping, the 24 tagSNPs were preliminarily assessed in a screening population of 552 controls, 254 GA and 236 GC subjects; subsequently, five candidate tagSNPs for gastric diseases risk in the TLR4, PGC and PTPN11 genes were re-evaluated in a larger population of 1276 controls, 907GA and 714 GC subjects. We observed that PGC rs6458238, PGC rs4711690 and PTPN11 rs12229892 were associated with susceptibilities to GA and/or GC. Moreover, rs4711690 and rs12229892 and H.pylori demonstrated significant interaction effects on GA risk. In gastric cancerous specimens, we observed significantly higher messenger RNA level in the subjects carrying the PGC rs6458238 GA genotype than that in subjects with the common GG genotype. These findings indicated that genetic variations of two crucial H.pylori-related host genes, H.pylori’s mucosal effecter PGC gene and H.pylori’s cellular messenger PTPN11 gene, either dependent or independent of interaction with H.pylori, were associated with the risks of GC and/or GA that precede carcinoma. Functional studies and further independent large-scale studies especially in other ethnic populations are still needed to confirm our results.
原文出处:
http://carcin.oxfordjournals.org/content/34/7/1450.abstract