Impact of pepsinogen C polymorphism on individual susceptibility to gastric cancer and its precancerous conditions in a Northeast Chinese population

Abstract

Purpose: 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.

Fig. 1

Genotype of the PGC gene polymorphism. a PGC gene polymorphisms determined by PCR and agarose gel electrophoresis. M DNA molecular weight marker, subject 1 310 bp/310 bp genotype, subject 2 and 6 450 bp/450 bp genotype, subjects 3, 4 and 7 310 bp/450 bp genotype, subjects 5 480 bp/480 bp genotype. b PGC gene polymorphisms determined by DNA sequencing