Impact of pepsinogen C polymorphism on individual susceptibility to gastric cancer and its precancerous conditions in a Northeast Chinese population.
OBJECTIVE
Human pepsinogen C (PGC) is an aspartic protease produced specifically by the gastric mucosa, and is considered as a mature marker of gastric epithelium. This study examined the contributions of PGC polymorphisms and the Helicobacter pylori (H. pylori) infection to the risk of gastric cancer (GC), and its precancerous conditions in a Northeast Chinese population.


METHODS
The PGC insertion/deletion polymorphism was evaluated by polymerase chain reaction analysis, followed by direct DNA sequencing in 564 cases of GC, atrophic gastritis (AG), gastric ulcer (GU) and superficial gastritis (as control). All cases were frequency-matched 1:1 by gender and age (+/-5). H. pylori infection was identified by serum anti-H. pylori IgG measurement through enzyme-linked immunosorbent assay.


RESULTS
Patients with a homozygous PGC allele 1 genotype had a significant risk of AG [adjusted odds ratio (OR) 3.11; 95% confidence interval (CI) 1.44-6.71] or of GC (OR 3.00; 95% CI 1.38-6.51), and a significantly elevated risk of intestinal metaplasia (OR 1.90, 95% CI 1.11-3.27). PGC polymorphism with H. pylori infection increased risk of GU (OR 8.69; 95% CI 1.01-74.69), and AG (OR 11.12; 95% CI 1.37-90.84) or GC (OR 10.61; 95% CI 1.28-87.79) in a super-multiplicative manner. The S value was 5.40, 6.48 and 4.34; and the AP value was 72.09, 7.00 and 69.69%, respectively.


CONCLUSIONS
The PGC gene polymorphism increases an individual's susceptibility to GC and its precancerous conditions. Moreover, the PGC gene polymorphism shows a positive link to H. pylori infection in the development of GC.
Sun
Li-Ping
LP
Cancer Institute, The First Affiliated Hospital of China Medical University, 155 N. Nanjing St., Heping District, 110001 Shenyang, China.
Guo
Xiao-Lin
XL
Zhang
Ye
Y
Chen
Wei
W
Bai
Xue-Lei
XL
Liu
Jin
J
Yuan
Yuan
Y
D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D004797:Enzyme-Linked Immunosorbent Assay; D005757:Gastritis, Atrophic / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D016481:Helicobacter Infections / Q000235:genetics; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D020115:Pepsinogen C / Q000235:genetics*; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000208:ethnology / Q000235:genetics*; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics*; D013276:Stomach Ulcer / Q000235:genetics
D020115:Pepsinogen C