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 η isozyme of protein kinase C (PKCη), 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% confidence interval, 1.11–5.05) relative to the GG genotype. The genotype was not associated with the risk of GC.
Conclusion
This was the first 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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ohata H, Kitauchi S, Yoshimura N, Mugitani K, Iwane M, Nakamura H, et al. Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. Int J Cancer 2004;109:138–143.
Caputo S, Mosca F, Persi A, Ettaro G, Scaringi S, Russo G, et al. Helicobacter pylori and gastric cancer. The incidence of infection in personal experience. Minerva Chir 2002;57:649–655.
Correa P, Haenszel W, Cuello C, Tannenbaum S, Archer M. A model for gastric cancer epidemiology. Lancet 1975;II:58–59.
Correa P, Piazuelo MB. Natural history of Helicobacter pylori infection. Dig Liver Dis 2008;40:490–496.
Palli D. Epidemiology of gastric cancer: an evaluation of available evidence. J Gastroenterol 2000;35:84–89.
Goto Y, Ando T, Yamamoto K, Tamakoshi A, El-Omar E, Goto H, et al. Association between serum pepsinogens and polymorphism of PTPN11 encoding SHP-2 among Helicobacter pylori seropositive Japanese. Int J Cancer 2006;118:203–208.
Goto Y, Ando T, Naito M, Goto H, Hamajima N. Inducible nitric oxide synthase polymorphism is associated with the increased risk of differentiated gastric cancer in a Japanese population. World J Gastroenterol 2006;12:6361–6365.
Goto Y, Ando T, Nishio K, Kawai S, Ishida Y, Naito M, et al. Grb2-associated binder 1 polymorphism was associated with the risk of Helicobacter pylori infection and gastric atrophy. Int J Med Sci 2006;4:–6.
Hishida A, Matsuo K, Goto Y, Mitsuda Y, Hiraki A, Naito M, et al. Toll-like receptor 4 +3725 G/C polymorphism, Helicobacter pylori seropositivity, and the risk of gastric atrophy and gastric cancer in Japanese. Helicobacter 2009;14:47–53.
Pham TN, Rahman P, Tobin YM, Khraishi MM, Hamilton SF, Alderdice C, et al. Elevated serum nitric oxide levels in patients with inflammatory arthritis associated with co-expression of inducible nitric oxide synthase and protein kinase C-eta in peripheral blood monocyte-derived macrophages. J Rheumatol 2003;30:2529–2534.
Goto T, Haruma K, Kitadai Y, Ito M, Yoshihara M, Sumii K, et al. Enhanced expression of inducible nitric oxide synthase and nitrotyrosine in gastric mucosa of gastric cancer patients. Clin Cancer Res 1999;5:1411–1415.
Pignatelli B, Bancel B, Estève J, Malaveille C, Calmels S, Correa P, et al. Inducible nitric oxide synthase, anti-oxidant enzymes and Helicobacter pylori infection in gastritis and gastric precancerous lesions in humans. Eur J Cancer Prev 1998;7:439–447.
Bagchi D, Bhattacharya G, Stohs SJ. Production of reactive oxygen species by gastric cells in association with Helicobacter pylori. Free Radic Res 1996;24:439–450.
Uht RM, Amos S, Martin PM, Riggan AE, Hussaini IM. The protein kinase C-eta isoform induces proliferation in glioblastoma cell lines through an ERK/Elk-1 pathway. Oncogene 2007;26:2885–2893.
Aeder SE, Martin PM, Soh JW, Hussaini IM. PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways. Oncogene 2004;23:9062–9069.
Takata Y, Hamada D, Miyatake K, Nakano S, Shinomiya F, Scafe CR, et al. Genetic association between the PRKCH gene encoding protein kinase Ceta isozyme and rheumatoid arthritis in the Japanese population. Arthritis Rheum 2007;56:30–42.
Kubo M, Hata J, Ninomiya T, Matsuda K, Yonemoto K, Nakano T, et al. A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nat Genet 2007;39:212–217.
Serizawa M, Nabika T, Ochiai Y, Takahashi K, Yamaguchi S, Makaya M, et al. Association between PRKCH gene polymorphisms and subcortical silent brain infarction. Atherosclerosis 2008;199:340–345.
Inoue M, Tajima K, Hirose K, Kuroishi T, Gao CM, Kitoh T. Lifestyle and subsite of gastric cancer-joint effect of smoking and drinking habits. Int J Cancer 1994;56:494–499.
Takezaki T, Hirose K, Inoue M, Hamajima N, Yatabe Y, Mitsudomi T, et al. Dietary factors and lung cancer risk in Japanese: with special reference to fish consumption and adenocarcinomas. Br J Cancer 2001;84:1199–1206.
Yang CX, Takezaki T, Hirose K, Inoue M, Huang XE, Tajima K. Fish consumption and colorectal cancer: a case-reference study in Japan. Eur J Cancer Prev 2003;12:109–115.
Nathan C. Inducible nitric oxide synthase: what difference does it make? J Clin Invest 1997;100:2417–2423.
Wink DA, Mitchell JB. Chemical biology of nitric oxide: insights into regulatory, cytotoxic and cytoprotective mechanisms of nitric oxide. Free Rad Biol Med 1998;25:434–456.
Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996;271:C1424–C1437.
Fima E, Shtutman M, Libros P, Missel A, Shahaf G, Kahana G, et al. PKCeta enhances cell cycle progression, the expression of G1 cyclins and p21 in MCF-7 cells. Oncogene 2001;20:6794–6804.
Kashiwagi M, Ohba M, Watanabe H, Ishino K, Kasahara K, Sanai Y, et al. PKCeta associates with cyclin E/cdk2/p21 complex, phosphorylates p21 and inhibits cdk2 kinase in keratinocytes. Oncogene 2000;19:6334–6341.
Asaka M, Sugiyama T, Nobuta A, Kato M, Takeda H, Graham DY. Atrophic gastritis and metaplasia in Japan: results of a large multicenter study. Helicobacter 2000;6:294–299.
Lambert JR, Lin SK, Aranda-Michel J. Helicobacter pylori. Scand J Gastroenterol 1995;208:33–46.
Freeman HJ. Disappearance of Helicobacter without antibiotics in 12 patients with gastritis. Can J Gastroenterol 1997;11:167–172.
Bair MJ, Wu MS, Chang WH, Shih SC, Wang TE, Chen CJ, et al. Spontaneous clearance of Helicobacter pylori colonization in patients with partial gastrectomy: correlates with operative procedures and duration after operation. J Formos Med Assoc 2009;108:13–19.
**a HH, Talley NJ. Natural acquisition and spontaneous elimination of Helicobacter pylori infection: clinical implications. Am J Gastroenterol 1997;92:1780–1787.
Iijima K, Koike T, Sekine H, Abe Y, Asanuma K, Ara N, et al. Sustained epithelial proliferation in a functionally irreversible fundic mucosa after Helicobacter pylori eradication. J Gastroenterol 2009;44:47–55.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Goto, Y., Hishida, A., Matsuo, K. et al. PRKCH gene polymorphism is associated with the risk of severe gastric atrophy. Gastric Cancer 13, 90–94 (2010). https://doi.org/10.1007/s10120-009-0542-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10120-009-0542-7