Main Article Content
Introduction: Genetic factors play an important role in the development of gastric cancer (GC), a prevalent malignancy in Central Asia. Recent studies have shown that single-nucleotide polymorphisms (SNPs) in several genes are associated with increased GC risk, indicating that genetic variation contributes to gastric carcinogenesis. Located on chromosome 8q24.2, the prostate stem cell antigen (PSCA) gene encodes a 123-amino acid glycoprotein related to the cell-proliferation inhibition and cell-death induction activity. SNPs in PSCA gene have been found to be associated with gastric cancer risk in a genome-wide association study, but results were not conclusive. This study aimed to investigate the association between two polymorphic variants of PSCA gene (rs2294008 and rs9297976) and the susceptibility to gastric cancer in Uzbekistan.
Methods: Two hundred sixty eight patients with gastric cancer and a control group of 248 healthy individuals were included in this study. DNA samples isolated from these groups were genotyped using PCR-RFLP method. Comparative analysis of resulting genotypes showed a statistically significant association between CT genotype and gastric cancer (p=0.03, additive model of inheritance, Cochran-Armitage trend test).
Results: Comparative analysis of the distribution of genotypes of rs2976392 polymorphism did not show a statistically significant difference; however, analysis of the distribution of the rs2976392 genotypes in a subgroup of young women revealed a statistically significant (p = 0.04, additive model of inheritance, Cochran-Armitage trend test) increase in the incidence of AA (38%) and AG (56%) genotypes in patients with GC, compared to the controls (20% and 40%).
Conclusion: Our findings support that PSCA rs2294008 and rs9297976 polymorphism may contribute to the susceptibility to gastric cancer. Genotyping of these polymorphisms can potentially be recommended as one of the criteria for identification of high risk groups for gastric cancer development in Uzbekistan.
Authors who publish with this journal agree to the following terms:
- The Author retains copyright in the Work, where the term “Work” shall include all digital objects that may result in subsequent electronic publication or distribution.
- Upon acceptance of the Work, the author shall grant to the Publisher the right of first publication of the Work.
- The Author shall grant to the Publisher and its agents the nonexclusive perpetual right and license to publish, archive, and make accessible the Work in whole or in part in all forms of media now or hereafter known under a Creative Commons Attribution 4.0 International License or its equivalent, which, for the avoidance of doubt, allows others to copy, distribute, and transmit the Work under the following conditions:
- Attribution—other users must attribute the Work in the manner specified by the author as indicated on the journal Web site;
- The Author is able to enter into separate, additional contractual arrangements for the nonexclusive distribution of the journal's published version of the Work (e.g., post it to an institutional repository or publish it in a book), as long as there is provided in the document an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post online a prepublication manuscript (but not the Publisher’s final formatted PDF version of the Work) in institutional repositories or on their Websites prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. Any such posting made before acceptance and publication of the Work shall be updated upon publication to include a reference to the Publisher-assigned DOI (Digital Object Identifier) and a link to the online abstract for the final published Work in the Journal.
- Upon Publisher’s request, the Author agrees to furnish promptly to Publisher, at the Author’s own expense, written evidence of the permissions, licenses, and consents for use of third-party material included within the Work, except as determined by Publisher to be covered by the principles of Fair Use.
- The Author represents and warrants that:
- the Work is the Author’s original work;
- the Author has not transferred, and will not transfer, exclusive rights in the Work to any third party;
- the Work is not pending review or under consideration by another publisher;
- the Work has not previously been published;
- the Work contains no misrepresentation or infringement of the Work or property of other authors or third parties; and
- the Work contains no libel, invasion of privacy, or other unlawful matter.
- The Author agrees to indemnify and hold Publisher harmless from Author’s breach of the representations and warranties contained in Paragraph 6 above, as well as any claim or proceeding relating to Publisher’s use and publication of any content contained in the Work, including third-party content.
Revised 7/16/2018. Revision Description: Removed outdated link.
World Cancer Research Fund Internaltional Stomach Cancer Statistics. 2012; http://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/stomach-cancer-statistics. Accessed June 9, 2016.
Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12(3):354-362.
Machii R, Saika K. Burden of cancer in Asia extrapolated from the WHO mortality database. Jpn J Clin Oncol. 2013;43(2):218.
Fock KM, Ang TL. Epidemiology of Helicobacter pylori infection and gastric cancer in Asia. J Gastroenterol Hepatol. 2010;25(3):479-486.
Yu Y, Assesorva, V, Kireev, G. The role of several nutritional factors in causing gastric cancer in city-dwellers of Uzbekistan. Oncosurgery. 2012;4(1):76-79.
Kawabata Y, Aparin, V, Nagai, M, Fujii, Y, Yamada, M, Hirano, T, Onwona-Agyeman, S, Katayama, Y. Changes in water quality of Amu-Darya river and ground water in Karakalpakstan, Uzbekistan. J of Arid Land Studies. 2015;25(3):125-128.
Kim J, Cho YA, Choi WJ, Jeong SH. Gene-diet interactions in gastric cancer risk: a systematic review. World J Gastroenterol. 2014;20(28):9600-9610.
Reiter RE, Gu Z, Watabe T, et al. Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer. Proc Natl Acad Sci U S A. 1998;95(4):1735-1740.
Sakamoto H, Yoshimura K, Saeki N, et al. Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. Nat Genet. 2008;40(6):730-740.
Tran CP, Lin C, Yamashiro J, Reiter RE. Prostate stem cell antigen is a marker of late intermediate prostate epithelial cells. Mol Cancer Res. 2002;1(2):113-121.
Saeki N, Gu J, Yoshida T, Wu X. Prostate stem cell antigen: a Jekyll and Hyde molecule? Clin Cancer Res. 2010;16(14):3533-3538.
Lochhead P, Frank B, Hold GL, et al. Genetic variation in the prostate stem cell antigen gene and upper gastrointestinal cancer in white individuals. Gastroenterology. 2011;140(2):435-441.
Sala N, Munoz X, Travier N, et al. Prostate stem-cell antigen gene is associated with diffuse and intestinal gastric cancer in Caucasians: results from the EPIC-EURGAST study. Int J Cancer. 2012;130(10):2417-2427.
Song HR, Kim HN, Piao JM, et al. Association of a common genetic variant in prostate stem-cell antigen with gastric cancer susceptibility in a Korean population. Mol Carcinog. 2011;50(11):871-875.
Wang M, Bai J, Tan Y, et al. Genetic variant in PSCA predicts survival of diffuse-type gastric cancer in a Chinese population. Int J Cancer. 2011;129(5):1207-1213.
Zeng Z, Wu X, Chen F, et al. Polymorphisms in prostate stem cell antigen gene rs2294008 increase gastric cancer risk in Chinese. Mol Carcinog. 2011;50(5):353-358.
Juwon K, Yoonjung, K, Kyung AL. Ethnic differences in gastric cancer genetic susceptibility: Allele flips of interleukin gene. World J Gastroenterol. 2014;20(16):4558–4565.
Zhi W, Xue B, Wang L, et al. The MLH1 2101C>A (Q701K) variant increases the risk of gastric cancer in Chinese males. BMC Gastroenterol. 2011;11:133.
Kunisaki C, Akiyama H, Nomura M, et al. Clinicopathological features of gastric carcinoma in younger and middle-aged patients: a comparative study. J Gastrointest Surg. 2006;10(7):1023-1032.
Hsieh FJ, Wang YC, Hsu JT, Liu KH, Yeh CN. Clinicopathological features and prognostic factors of gastric cancer patients aged 40 years or younger. J Surg Oncol. 2012;105(3):304-309.
Bashar A, Khesar, HK, Zobayda, AS. Prevalence of intestinal metaplasia and dysplasia in infectious and non-infectious chronic gastritis. Int J Res Med Sci. 2015;3(9):2228-2231
IsoGen Life Science. 2016; http://www.isogen-lifescience.com. Accessed June 20, 2016.
Rothman N, Garcia-Closas M, Chatterjee N, et al. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nat Genet. 2010;42(11):978-984.
Wu X, Ye Y, Kiemeney LA, et al. Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer. Nat Genet. 2009;41(9):991-995.
Tanikawa C, Urabe Y, Matsuo K, et al. A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population. Nat Genet. 2012;44(4):430-434, S431-432.
Chandra V, Kim JJ, Gupta U, Mittal B, Rai R. Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism in Modulating Cancer Risk in Asian Population. Genes (Basel). 2016;7(2).
Gu Y, Dai QS, Hua RX, et al. PSCA s2294008 C>T and rs2976392 G>A polymorphisms contribute to cancer susceptibility: evidence from published studies. Genes Cancer. 2015;6(5-6):254-264.
Singh S, Poulsom, R, Wright, NA, Shephard, MC, Langman, MJS. Differential expression of oestrogen receptor and oestrogen inducible genes in gastric mucosa and cancer. Gut. 1997;40:516-520.
Johansson J, Thulin L, Ferno M, Andren-Sandberg A. Estrogen receptors in gastric cancer. Acta Oncol. 1991;30(7):870-872.
Merrell KW CJ, Smith RL, Sin JH, Kmetzsch KE, Merrell A, Miguel RO, Candelaria NR, Lin CY. Differential recruitment of nuclear receptor coregulators in ligand-dependent transcriptional repression by estrogen receptor-a. Oncogene. 2011;30:1608–1614.