COX-2-765 G > C (rs20417) Gene Polymorphism and the Risk of Gastric Cancer: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 TANHui ¹ , CUIJing ¹ , JIANGLei ² , YUANWen-zhen ² ,  GUANQuan-lin ²

1. First Clinical Medical College of Lanzhou University, Lanzhou 730000, China;
2. Department of Oncological Surgery, First Hospital of Lanzhou University, Lanzhou 730000, China;

Corresponding author：

GUANQuan-lin, Email: guanquanlinwy@163.com

Keywords：

Gastric Cancer; Polymorphism; Cyclooxygenase-2 (COX-2); Risk; Meta-analysis

DOI：

10.7507/1672-2531.20160193

Video：

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Objective To systematically review the association between -765 G > C (rs20417) polymorphism of cyclooxygenase-2 (COX-2) gene and the risk of gastric cancer (GC). Methods Such databases as PubMed, EMbase, The Cochrane Library (Issue 10, 2015), CBM, CNKI, VIP and WanFang Data were searched from inception to October 2015 to collect case-control studies about the correlation between -765 G > C (rs20417) polymorphism of COX-2 gene and GC. Two reviewers independently screened literature, extracted data and evaluated the quality of included studies. Meta-analysis was performed using Stata 12.0 software. Results A total of 15 case-control studies were included in this meta-analysis, including 2 891 cases and 4 967 controls. Meta-analysis showed that the -765 G > C (rs20417) polymorphism was significantly associated with the risk of GC (OR=1.70, 95%CI 1.21 to 2.38, P=0.002). Subgroup analysis showed there was a significant association between the -765 G > C (rs20417) polymorphism and GC in Asians (OR=2.24, 95%CI 1.70 to 2.96, P=0.000); However, no association was found in the Caucasians and Americans. In the subgroup analysis by Helicobacter pylori (H. pylori) status, there were statistical significances between helicobacter pylori (+) and helicobacter pylori (-) with the risk of GC in COX-2 polymorphism of CC/CG vs. GG (OR=2.11, 95%CI 1.41 to 3.14, P < 0.001). Conclusion The COX-2-765 G > C (rs20417) polymorphism may be significantly associated with an increased risk of GC, especially among Asians.

Citation： TANHui, CUIJing, JIANGLei, YUANWen-zhen, GUANQuan-lin. COX-2-765 G > C (rs20417) Gene Polymorphism and the Risk of Gastric Cancer: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2016, 16(11): 1270-1275. doi: 10.7507/1672-2531.20160193 Copy

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2.	Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2):87-108.
3.	陈万青, 郑荣寿, 张思维, 等. 2012年中国恶性肿瘤发病和死亡分析.中国肿瘤, 2016, (1):1-8.
4.	Gonzalez CA, Sala N, Rokkas T. Gastric cancer:epidemiologic aspects. Helicobacter, 2013, 18 Suppl 1:34-38.
5.	Guggenheim DE, Shah MA. Gastric cancer epidemiology and risk factors. J Surg Oncol, 2013, 107(3):230-236.
6.	Gao F, Lu L, Qin J, et al. Single Nucleotide Polymorphism in COX-2 Gene are Associated with Risk of Non-cardia Gastric Cancer. Cancer Res Pre Treat, 2015, 42(5):470-473.
7.	Lu XR, Chen FY, Liu XW, et al. Detection and Clinical Significance of COX-2 Gene SNPs in Gastric Cancer. Cell Biochem and Biophys, 2015, 72(3):657-660.
8.	Bakhle YS. COX-2 and cancer:a new approach to an old problem. Br J Pharmacol, 2001, 134(6):1137-1150.
9.	Sun WH, Sun YL, Fang RN, et al. Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis. Jpn J Clin Oncol, 2005, 35(12):707-713.
10.	Misra S, Sharma K. COX-2 signaling and cancer:new players in old arena. Curr Drug Targets, 2014, 15(3):347-359.
11.	Kim NK, Park JK, Shin E, et al. The combination of nuclear factor kappa B, cyclo-oxygenase-2 and vascular endothelial growth factor expression predicts poor prognosis in stage II and III colorectal cancer. Anticancer Res, 2014, 34(11):6451-6457.
12.	Yu J, Leung WK, Chen J, et al. Expression of peroxisome proliferator-activated receptor delta in human gastric cancer and its response to specific COX-2 inhibitor. Cancer Lett, 2005, 223(1):11-17.
13.	Dixon DA. Regulation of COX-2 expression in human cancers. Prog Exp Tumor Res, 2003, 37:52-71.
14.	Sonoda R, Naomoto Y, Shirakawa Y, et al. Preferential up-regulation of heparanase and cyclooxygenase-2 in carcinogenesis of Barrett's oesophagus and intestinal-type gastric carcinoma. Histopathology, 2010, 57(1):90-100.
15.	Hou L, Grillo P, Zhu ZZ, et al. COX1 and COX2 polymorphisms and gastric cancer risk in a Polish population. Anticancer Res, 2007, 27(6C):4243-4247.
16.	Zhang XM, Zhong R, Liu L, et al. Smoking and COX-2 functional polymorphisms interact to increase the risk of gastric cardia adenocarcinoma in Chinese population. PLoS One, 2011, 6(7):e21894.
17.	Cook DA, Reed DA. Appraising the quality of medical education research methods:the Medical Education Research Study Quality Instrument and the Newcastle-Ottawa Scale-Education. Acad Med, 2015, 90(8):1067-1076.
18.	王丹, 翟俊霞, 牟振云, 等. Meta分析中的异质性及其处理方法.中国循证医学杂志, 2009, 9(10):1115-1118.
19.	Liu F, Pan K, Zhang X, et al. Genetic variants in cyclooxygenase-2:Expression and risk of gastric cancer and its precursors in a Chinese population. Gastroenterology, 2006, 130(7):1975-1984.
20.	张雪梅, 缪小平, 谭文, 等.环氧化酶2启动子区遗传变异及其与胃癌发病风险的关系.中国医学科学院学报, 2006, 28(2):119-123.
21.	Saxena A, Prasad KN, Ghoshal UC, et al. Polymorphism of -765G>C COX-2 is a risk factor for gastric adenocarcinoma and peptic ulcer disease in addition to H pylori infection:a study from northern India. World J Gastroenterol, 2008, 14(10):1498-1503.
22.	唐小凡, 李玉民, 李世雄, 等.环氧化酶-2基因多态性与回族人群胃癌易感性的关联.世界华人消化杂志, 2009, 17(17):1772-1776.
23.	张丹.胃癌高低发区COX-2、PARP-1基因多态性与胃癌相关性的研究.兰州:兰州大学, 2009.
24.	Zhang X, Zhong R, Zhang Z, et al. Interaction of cyclooxygenase-2 promoter polymorphisms with Helicobacter pylori infection and risk of gastric cancer. Mol Carcinog, 2011, 50(11):876-883.
25.	Shin WG, Kim HJ, Cho SJ, et al. The COX-2-1195AA Genotype Is Associated with Diffuse-Type Gastric Cancer in Korea. Gut Liver, 2012, 6(3):321-327.
26.	Li Y, Dai L, Zhang J, et al. Cyclooxygenase-2 polymorphisms and the risk of gastric cancer in various degrees of relationship in the Chinese Han population. Oncol Lett, 2012, 3(1):107-112.
27.	He WT, Liu T, Tang XF, et al. The COX-2-765 G>C polymorphism is associated with increased risk of gastric carcinogenesis in the Chinese Hui ethnic population. Asian Pac J Cancer Prev, 2014, 15(9):4067-4070.
28.	陶梅, 张玲霞, 宋瑛, 等.陕西地区环氧化酶-2基因的多态性、螺杆菌感染与胃癌易感性的关系.山西医科大学学报, 2015, 46(1):17-21.
29.	Pereira C, Sousa H, Ferreira P, et al.-765G>C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia. World J Gastroenterol, 2006, 12(34):5473-5478.
30.	Sitarz R, Leguit RJ, de Leng WW, et al. The COX-2 promoter polymorphism-765 G>C is associated with early-onset, conventional and stump gastric cancers. Mod Pathol, 2008, 21(6):685-690.
31.	Campanholo VM, Felipe AV, de Lima JM, et al.-765 g>c polymorphism of the cox-2 gene and gastric cancer risk in Brazilian population. Arq Gastroenterol, 2014, 51(2):79-83.
32.	Wang XF, Huang MZ, Zhang XW, et al. COX-2-765G>C polymorphism increases the risk of cancer:a meta-analysis. PLoS One, 2013, 8(9):e73213.
33.	Lu X, Chen F, Liu X, et al. Detection and Clinical Significance of COX-2 Gene SNPs in Gastric Cancer. Cell Biochem and Biophys, 2015, 73(3):657-660.
34.	Su HJ, Zhang Y, Zhang L, et al. Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population. BMC Cancer, 2015, 979(15):1-8.
35.	Kotnis A, Sarin R, Mulherkar R. Genotype, phenotype and cancer:role of low penetrance genes and environment in tumour susceptibility. J Biosci, 2005, 30(1):93-102.
36.	Malysheva V, Mendoza-Parra MA, Saleem MA, et al. Reconstruction of gene regulatory networks reveals chromatin remodelers and key transcription factors in tumorigenesis. Genome Med, 2016, 8(1):PMC4872343.

1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61(2):69-90.
2. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2):87-108.
3. 陈万青, 郑荣寿, 张思维, 等. 2012年中国恶性肿瘤发病和死亡分析.中国肿瘤, 2016, (1):1-8.
4. Gonzalez CA, Sala N, Rokkas T. Gastric cancer:epidemiologic aspects. Helicobacter, 2013, 18 Suppl 1:34-38.
5. Guggenheim DE, Shah MA. Gastric cancer epidemiology and risk factors. J Surg Oncol, 2013, 107(3):230-236.
6. Gao F, Lu L, Qin J, et al. Single Nucleotide Polymorphism in COX-2 Gene are Associated with Risk of Non-cardia Gastric Cancer. Cancer Res Pre Treat, 2015, 42(5):470-473.
7. Lu XR, Chen FY, Liu XW, et al. Detection and Clinical Significance of COX-2 Gene SNPs in Gastric Cancer. Cell Biochem and Biophys, 2015, 72(3):657-660.
8. Bakhle YS. COX-2 and cancer:a new approach to an old problem. Br J Pharmacol, 2001, 134(6):1137-1150.
9. Sun WH, Sun YL, Fang RN, et al. Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis. Jpn J Clin Oncol, 2005, 35(12):707-713.
10. Misra S, Sharma K. COX-2 signaling and cancer:new players in old arena. Curr Drug Targets, 2014, 15(3):347-359.
11. Kim NK, Park JK, Shin E, et al. The combination of nuclear factor kappa B, cyclo-oxygenase-2 and vascular endothelial growth factor expression predicts poor prognosis in stage II and III colorectal cancer. Anticancer Res, 2014, 34(11):6451-6457.
12. Yu J, Leung WK, Chen J, et al. Expression of peroxisome proliferator-activated receptor delta in human gastric cancer and its response to specific COX-2 inhibitor. Cancer Lett, 2005, 223(1):11-17.
13. Dixon DA. Regulation of COX-2 expression in human cancers. Prog Exp Tumor Res, 2003, 37:52-71.
14. Sonoda R, Naomoto Y, Shirakawa Y, et al. Preferential up-regulation of heparanase and cyclooxygenase-2 in carcinogenesis of Barrett's oesophagus and intestinal-type gastric carcinoma. Histopathology, 2010, 57(1):90-100.
15. Hou L, Grillo P, Zhu ZZ, et al. COX1 and COX2 polymorphisms and gastric cancer risk in a Polish population. Anticancer Res, 2007, 27(6C):4243-4247.
16. Zhang XM, Zhong R, Liu L, et al. Smoking and COX-2 functional polymorphisms interact to increase the risk of gastric cardia adenocarcinoma in Chinese population. PLoS One, 2011, 6(7):e21894.
17. Cook DA, Reed DA. Appraising the quality of medical education research methods:the Medical Education Research Study Quality Instrument and the Newcastle-Ottawa Scale-Education. Acad Med, 2015, 90(8):1067-1076.
18. 王丹, 翟俊霞, 牟振云, 等. Meta分析中的异质性及其处理方法.中国循证医学杂志, 2009, 9(10):1115-1118.
19. Liu F, Pan K, Zhang X, et al. Genetic variants in cyclooxygenase-2:Expression and risk of gastric cancer and its precursors in a Chinese population. Gastroenterology, 2006, 130(7):1975-1984.
20. 张雪梅, 缪小平, 谭文, 等.环氧化酶2启动子区遗传变异及其与胃癌发病风险的关系.中国医学科学院学报, 2006, 28(2):119-123.
21. Saxena A, Prasad KN, Ghoshal UC, et al. Polymorphism of -765G>C COX-2 is a risk factor for gastric adenocarcinoma and peptic ulcer disease in addition to H pylori infection:a study from northern India. World J Gastroenterol, 2008, 14(10):1498-1503.
22. 唐小凡, 李玉民, 李世雄, 等.环氧化酶-2基因多态性与回族人群胃癌易感性的关联.世界华人消化杂志, 2009, 17(17):1772-1776.
23. 张丹.胃癌高低发区COX-2、PARP-1基因多态性与胃癌相关性的研究.兰州:兰州大学, 2009.
24. Zhang X, Zhong R, Zhang Z, et al. Interaction of cyclooxygenase-2 promoter polymorphisms with Helicobacter pylori infection and risk of gastric cancer. Mol Carcinog, 2011, 50(11):876-883.
25. Shin WG, Kim HJ, Cho SJ, et al. The COX-2-1195AA Genotype Is Associated with Diffuse-Type Gastric Cancer in Korea. Gut Liver, 2012, 6(3):321-327.
26. Li Y, Dai L, Zhang J, et al. Cyclooxygenase-2 polymorphisms and the risk of gastric cancer in various degrees of relationship in the Chinese Han population. Oncol Lett, 2012, 3(1):107-112.
27. He WT, Liu T, Tang XF, et al. The COX-2-765 G>C polymorphism is associated with increased risk of gastric carcinogenesis in the Chinese Hui ethnic population. Asian Pac J Cancer Prev, 2014, 15(9):4067-4070.
28. 陶梅, 张玲霞, 宋瑛, 等.陕西地区环氧化酶-2基因的多态性、螺杆菌感染与胃癌易感性的关系.山西医科大学学报, 2015, 46(1):17-21.
29. Pereira C, Sousa H, Ferreira P, et al.-765G>C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia. World J Gastroenterol, 2006, 12(34):5473-5478.
30. Sitarz R, Leguit RJ, de Leng WW, et al. The COX-2 promoter polymorphism-765 G>C is associated with early-onset, conventional and stump gastric cancers. Mod Pathol, 2008, 21(6):685-690.
31. Campanholo VM, Felipe AV, de Lima JM, et al.-765 g>c polymorphism of the cox-2 gene and gastric cancer risk in Brazilian population. Arq Gastroenterol, 2014, 51(2):79-83.
32. Wang XF, Huang MZ, Zhang XW, et al. COX-2-765G>C polymorphism increases the risk of cancer:a meta-analysis. PLoS One, 2013, 8(9):e73213.
33. Lu X, Chen F, Liu X, et al. Detection and Clinical Significance of COX-2 Gene SNPs in Gastric Cancer. Cell Biochem and Biophys, 2015, 73(3):657-660.
34. Su HJ, Zhang Y, Zhang L, et al. Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population. BMC Cancer, 2015, 979(15):1-8.
35. Kotnis A, Sarin R, Mulherkar R. Genotype, phenotype and cancer:role of low penetrance genes and environment in tumour susceptibility. J Biosci, 2005, 30(1):93-102.
36. Malysheva V, Mendoza-Parra MA, Saleem MA, et al. Reconstruction of gene regulatory networks reveals chromatin remodelers and key transcription factors in tumorigenesis. Genome Med, 2016, 8(1):PMC4872343.

Chinese Journal of Evidence-Based Medicine

COX-2-765 G > C (rs20417) Gene Polymorphism and the Risk of Gastric Cancer: A Meta-analysis

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