title: Helicobacter pylori-related host gene polymorphisms associated with susceptibility of gastric carcinogenesis: a two-stage case-control study in Chinese.
abstract: 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.
authors: Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, Key Laboratory of Tumor Etiology and Prevention in Liaoning Province, Shenyang 110001, China.
authors: Caiyun
authors: C
authors: He
authors: Huakang
authors: H
authors: Tu
authors: Liping
authors: L
authors: Sun
authors: Qian
authors: Q
authors: Xu
authors: Ping
authors: P
authors: Li
authors: Yuehua
authors: Y
authors: Gong
authors: Nannan
authors: N
authors: Dong
authors: Yuan
authors: Y
authors: Yuan
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005757:Gastritis, Atrophic / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020115:Pepsinogen C / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D020115:Pepsinogen C; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11