PRKCH gene polymorphism is associated with the risk of severe gastric atrophy

Abstract

Background. Individuals infected with Helicobacter pylori do not necessarily develop gastric atrophy (GA) and gastric cancer (GC). Several factors, including genetic polymorphism, can regulate the development of GA and GC. A G/A single nucleotide polymorphism (rs3783799) of the PRKCH gene, which encodes the ? isozyme of protein kinase C (PKC?), has been reported to be a tag single nucleotide polymorphism (SNP) of the PRKCH gene linked to a functional 1425G/A SNP in exon 9 (rs2230500). To elucidate its applicability in the development of GA and GC, this study aimed to investigate the associations of the PRKCH polymorphism with the risks of GA and GC. Methods. The subjects consisted of 583 patients (cases) from first-visit outpatients at Aichi Cancer Center Hospital, aged 27 to 80 years, who were diagnosed as having GC from 2001 to 2005, and 1742 controls, frequency-matched for age and sex. Anti-H. pylori IgG antibodies and pepsinogens (PGs) in serum were measured for 1638 controls. Results. Of the 1638 controls, 57.3% were seropositive and 33.0% had GA (PG1 ≤ 70 ng/dl and PG1/PG2 ≤ 3). When compared to the seronegative controls without GA, the AA genotype was significantly associated with severe GA (PG1 ≤ 30 ng/dl and PG1/PG2 ≤ 2); odds ratio (OR), 2.37 (95% confi dence interval, 1.11-5.05) relative to the GG genotype. The genotype was not associated with the risk of GC. Conclusion. This was the fi rst study to examine the associations of the PRKCH polymorphism with GA and GC, and suggested that the AA genotype, relative to the G/G genotype, may be a higher risk genotype for severe GA. © 2010 by International and Japanese Gastric Cancer Associations.