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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ando T, Goto Y, Ishiguro K et al (2007) The interaction of host genetic factors and Helicobacter pylori infection. Inflammopharmacology 15:10–14. doi:10.1007/s10787-006-1556-y
Azuma T, Teramae N, Hayakumo T et al (1993) Pepsinogen C gene polymorphisms associated with gastric body ulcer. Gut 34:450–455. doi:10.1136/gut.34.4.450
Bowcock AM, Azuma T, Barnes RI et al (1992) Detection of a polymorphism within pepsinogen C gene with PCR: construction of a linkage map around PGC from 6p11–6p21.3. Genomics 14:398–402. doi:10.1016/S0888-7543(05)80232-0
Correa P (1992) Human gastric carcinogenesis. A multistep and multifactorial process—first American Cancer Society Award Lecture on cancer epidemiology and prevention. Cancer Res 52:6735–6740
Correa P, Schneider BG (2005) Etiology of gastric cancer: what is new? Cancer Epidemiol Biomarkers Prev 14:1865–1868. doi:10.1158/1055-9965.EPI-05-0029
Dixon MF, Genta RM, Yardley JH et al (1996) Classification and grading of gastritis. The Updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 20:1161–1181
El-Omar EM, Carrington M, Chow WH et al (2000) Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404:398–402. doi:10.1038/35006081
Fernandez R, Vizoso F, Rodriguez JC et al (2000) Expression and prognostic significance of pepsinogen C in gastric carcinoma. Ann Surg Oncol 7:508–514. doi:10.1007/s10434-000-0508-9
González CA, Sala N, Capellá G (2002) Genetic susceptibility and gastric cancer risk. Int J Cancer 100:249–260. doi:10.1002/ijc.10466
Hohenberger P, Gretschel S (2003) Gastric cancer. Lancet 362:305–315. doi:10.1016/S0140-6736(03)13975-X
International Agency for Research on Cancer (1994) Schistosomes liver flukes and Helicobacter pylori IARC monographs on the evaluation of carcinogenic risks to humans, vol 61. IARC, Lyon, pp 177–240
Kishi K, Kinoshita Y, Matsushima Y et al (1997) Pepsinogen gene product is a possible growth factor during gastric mucosa healing. Biochem Biophys Res Commun 238:17–20. doi:10.1006/bbrc.1997.7231
Lin SR, Yu ZL, Hu PJ et al (2000) Consensus on chronic gastritis formulated at the national symposium. Zhonghua Xiaohua Zazhi 20:199–201
Liu HJ, Guo XL, Dong M et al (2003) Association between pepsinogen C gene polymorphism and genetic predisposition to gastric cancer. World J Gastroenterol 9:50–53
Li Z, Chen D, Zhang C et al (2005) HLA polymorphisms are associated with Helicobacter pylori infected gastric cancer in a high risk population, China. Immunogenetics 56:781–787. doi:10.1007/s00251-004-0723-9
Lorente S, Doiz O, Trinidad Serrano M et al (2002) Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells. Gut 50:13–18. doi:10.1136/gut.50.1.13
Melle C, Ernst G, Schimmel B et al (2005) Characterization of pepsinogen C as a potential biomarker for gastric cancer using a histo-proteomic approach. J Proteome Res 4:1799–1804. doi:10.1021/pr050123o
Mukoubayashi C, Yanaoka K, Ohata H et al (2007) Serum pepsinogen and gastric cancer screening. Intern Med 46:261–266. doi:10.2169/internalmedicine.46.6181
Ohtaka Y, Azuma T, Konishi J et al (1997) Association between genetic polymorphism of the pepsinogen C gene and gastric body ulcer: The genetic predisposition is not associated with Helicobacter pylori infection. Gut 41:469–474
Pals G, Azuma T, Mohandas TK et al (1989) Human pepsinogen C (progastricsin) polymorphism: evidence for a single locus located at 6p21.1-pter. Genomics 4:137–148. doi:10.1016/0888-7543(89)90292-9
Peek RM, Blaser MJ (2002) Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer 2:28–37. doi:10.1038/nrc703
Pinto-Correia AL, Sousa H, Fragoso M et al (2006) Gastric cancer in a Caucasian population: role of pepsinogen C genetic variants. World J Gastroenterol 12:5033–5036
Pinto-Santini D, Salama NR (2005) The biology of Helicobacter pylori infection, a major risk factor for gastric adenocarcinoma. Cancer Epidemiol Biomarkers Prev 14:1853–1858. doi:10.1158/1055-9965.EPI-04-0784
Samloff IM (1982) Pepsinogen I and II: purification from gastric mucosa and radioimmunoassay in serum. Gastroenterology 82:26–33
Starzynska T, Ferenc K, Wex T, Kahne T et al (2006) The association between the interleukin-1 polymorphisms and gastric cancer risk depends on the family history of gastric carcinoma in the study population. Am J Gastroenterol 101:248–254. doi:10.1111/j.1572-0241.2006.00422.x
Taguchi A, Ohmiya N, Shirai K et al (2005) Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan. Cancer Epidemiol Biomarkers Prev 14:2487–2493. doi:10.1158/1055-9965.EPI-05-0326
Uemura N, Okamoto S, Yamamoto S et al (2001) Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 345:784–789. doi:10.1056/NEJMoa001999
Yuan Y, Dong M, He AG et al (1996) Primary study on pepsinogen C polymorphism and screening population in high risk of gastric cancer. Zhonghua Yixue Zazhi 76:69–70
Acknowledgments
This work was supported by the National Natural Science Foundation of China, Grant 30572131 and 30700989.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sun, LP., Guo, XL., Zhang, Y. et al. Impact of pepsinogen C polymorphism on individual susceptibility to gastric cancer and its precancerous conditions in a Northeast Chinese population. J Cancer Res Clin Oncol 135, 1033–1039 (2009). https://doi.org/10.1007/s00432-008-0539-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-008-0539-3