Association between –174C/G genetic polymorphism of interleukin-6 and susceptibility to gastric cancer: a meta-analysis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Manxiang ¹ , SONG Chunfeng ² , ZHANG Baoying ¹ , JIANG Lei ³ ,  GUAN Quanlin ³

1. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of Hepatobiliary Surgery, General Hospital of Shenyang Military Command, Shenyang 110000, P. R. China;
3. Department of Oncological Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;

Corresponding author：

GUAN Quanlin, Email: guanquanlinwy@163.com

Keywords：

gastric cancer; genetic polymorphism; interleukin-6; susceptibility; meta-analysis

DOI：

10.7507/1007-9424.201705030

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Objective To investigate association between –174C/G genetic polymorphism of interleukin-6 (IL-6) and susceptibility to gastric cancer by conducting a meta-analysis. Methods Such databases as PubMed, Embase, The Cochrane Library, Web of Science, CNKI, VIP, and Wanfang Data were searched from inception to January 2017 to collect case-control studies about the correlation between the –174C/G genetic polymorphism of IL-6 and susceptibility to gastric cancer. For the population genotype distributions of both the gastric cancer group and the control group, their odds ratios (OR) and 95% confidence intervals (CI) were taken as the effect indexes were applied to conduct meta-analysis in the homozygote model (CC vs. GG), heterozygote model (GC vs. GG), dominant model (CC+CG vs. GG), recessive model (CG+GG vs. CC), and allelic genetic model (C vs. G). Two reviewers independently screened the literatures, extracted the data, and evaluated the quality of the included studies. The meta-analysis was performed using Stata 12.0 software. Results Thirteen articles were included in the final meta-analysis, covering a total of 2 062 gastric cancer cases and 3 152 controls. The results of meta-analysis showed that there was no correlation between the IL-6 –174C/G genetic polymorphism and the risk of gastric cancer〔CC vs. GG: OR=1.33, 95% CI (0.92, 1.94); GC vs. GG: OR=1.32, 95% CI (0.96, 1.82); CC+CG vs. GG: OR=1.32, 95% CI (0.97, 1.80); CG+GG vs. CC: OR=0.89, 95% CI (0.67, 1.17); C vs. G: OR=1.22, 95% CI (0.98, 1.54)〕. But the results of the subgroup analysis showed there was a significant association between the IL-6 –174 C/G genetic polymorphism and the risk of gastric cancer in Asians〔CC vs. GG: OR=1.80, 95% CI (1.29, 2.50); GC vs. GG: OR=1.51, 95% CI (1.20, 1.90); CC+CG vs. GG: OR=1.60, 95% CI (1.30, 1.96); CG+GG vs. CC: OR=0.60, 95% CI (0.44, 0.83); C vs. G: OR=1.59, 95% CI (1.24, 2.03)〕. However, no association was found in Europeans〔CC vs. GG: OR=1.11, 95% CI (0.90, 1.39); GC vs. GG: OR=1.16, 95% CI (0.98, 1.37); CC+CG vs. GG: OR=1.12, 95% CI (0.96, 1.32); CG+GG vs. CC: OR=1.07, 95% CI (0.88, 1.30); C vs. G: OR=1.04, 95% CI (0.78, 1.41)〕 . Conclusion IL-6 –174C/G genetic polymorphism is associated with susceptibility to gastric cancer in Asians, which is not associated with susceptibility to gastric cancer in Europeans.

Citation： LIU Manxiang, SONG Chunfeng, ZHANG Baoying, JIANG Lei, GUAN Quanlin. Association between –174C/G genetic polymorphism of interleukin-6 and susceptibility to gastric cancer: a meta-analysis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(10): 1234-1245. doi: 10.7507/1007-9424.201705030 Copy

1.	Sasako M, Inoue M, Lin JT, et al. Gastric cancer working group report. Jpn J Clin Oncol, 2010, 40 Suppl 1: i28-i37.
2.	左婷婷, 郑荣寿, 曾红梅, 等. 中国胃癌流行病学现状. 中国肿瘤临床, 2017, 44(1): 52-58.0.
3.	Savage SA, Abnet CC, Haque K, et al. Polymorphisms in interleukin -2, -6, and -10 are not associated with gastric cardia or esophageal cancer in a high-risk Chinese population. Cancer Epidemiol Biomarkers Prev, 2004, 13(9): 1547-1549.
4.	Macarthur M, Hold GL, El-Omar EM. Inflammation and cancer II. Role of chronic inflammation and cytokine gene polymorphisms in the pathogenesis of gastrointestinal malignancy. Am J Physiol Gastrointest Liver Physiol, 2004, 286(4): G515-G520.
5.	Li K, Xia F, Zhang K, et al. Association of a tgf-b1-509c/t polymorphism with gastric cancer risk: a meta-analysis. Ann Hum Genet, 2013, 77(1): 1-8.
6.	Fishman D, Faulds G, Jeffery R, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest, 1998, 102(7): 1369-1376.
7.	El-Omar EM, Rabkin CS, Gammon MD, et al. Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology, 2003, 124(5): 1193-1201.
8.	Hwang IR, Hsu PI, Peterson LE, Gutierrez O, et al. Interleukin-6 genetic polymorphisms are not related to Helicobacter pylori-associated gastroduodenal diseases. Helicobacter, 2003, 8(2): 142-148.
9.	Gatti LL, Burbano RR, Zambaldi-Tunes M, et al. Interleukin-6 polymorphisms, Helicobacter pylori infection in adult Brazilian patients with chronic gastritis and gastric adenocarcinoma. Arch Med Res, 2007, 38(5): 551-555.
10.	Kamangar F, Abnet CC, Hutchinson AA, et al. Polymorphisms in inflammation-related genes and risk of gastric cancer (Finland). Cancer Causes Control, 2006, 17(1): 117-125.
11.	Deans C, Rose-Zerilli M, Wigmore S, et al. Host cytokine genotype is related to adverse prognosis and systemic inflammation in gastro-oesophageal cancer. Ann Surg Oncol, 2007, 14(2): 329-339.
12.	Crusius JB, Canzian F, Capellá G, et al. Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST). Ann Oncol, 2008, 19(11): 1894-1902.
13.	邢培祥, 肖东杰, 曾庆东, 等. 细胞因子基因多态性与胃腺癌发生及其临床病理特点的关系. 中国普通外科杂志, 2006, 15(9): 659-663.0.
14.	赵勇, 肖滢, 高峰, 等. 甘肃武威地区胃癌发病风险与 IL-6 基因多态性的相关性研究. 临床军医杂志, 2010, 38(1): 25-27.0.
15.	王昆龄, 陈凡, 王晓莉. 白细胞介素-6 与胃癌易感性的相关关系. 现代预防医学, 2014, 41(18): 3450-3452.0.
16.	李湘楚, 熊建光, 程正位, 等. 白细胞介素-6 与胃癌易感性的相关研究. 胃肠病学和肝病学杂志, 2014, 23(6): 708-711.0.
17.	曹春莉. IL-6 174G/C 基因多态性与胃肿瘤易感性多因素分析研究. 现代预防医学, 2014, 41(20): 3756-3758, 3783.0.
18.	Pohjanen VM, Koivurova OP, Mäkinen JM, et al. Interleukin 6 gene polymorphism -174 is associated with the diffuse type gastric carcinoma. Genes Chromosomes Cancer, 2013, 52(10): 976-982.
19.	Sampaio AM, Balseiro SC, Silva MR, et al. Association between IL-4 and IL-6 expression variants and gastric cancer among portuguese population. GE Port J Gastroenterol, 2015, 22(4): 143-152.
20.	Guggenheim DE, Shah MA. Gastric cancer epidemiology and risk factors. J Surg Oncol, 2013, 107(3): 230-236.
21.	Bonequi P, Meneses-González F, Correa P, et al. Risk factors for gastric cancer in Latin America: a meta-analysis. Cancer Causes Control, 2013, 24(2): 217-231.
22.	Testa R, Olivieri F, Bonfigli AR, et al. Interleukin-6-174 G > C polymorphism affects the association between IL-6 plasma levels and insulin resistance in type 2 diabetic patients. Diabetes Res Clin Pract, 2006, 71(3): 299-305.
23.	Mandal S, Abebe F, Chaudhary J. -174G/C polymorphism in the interleukin-6 promoter is differently associated with prostate cancer incidence depending on race. Genet Mol Res, 2014, 13(1): 139-151.
24.	Kim JM, Stewart R, Kim SY, et al. A one year longitudinal study of cytokine genes and depression in breast cancer. J Affect Disord, 2013, 148(1): 57-65.
25.	Peng WJ, He Q, Yang JX, et al. Meta-analysis of association between cytokine gene polymorphisms and lung cancer risk. Mol Biol Rep, 2012, 39(5): 5187-5194.
26.	Giannitrapani L, Soresi M, Giacalone A, et al. IL-6 -174G/C polymorphism and IL-6 serum levels in patients with liver cirrhosis and hepatocellular carcinoma. OMICS, 2011, 15(3): 183-186.

1. Sasako M, Inoue M, Lin JT, et al. Gastric cancer working group report. Jpn J Clin Oncol, 2010, 40 Suppl 1: i28-i37.
2. 左婷婷, 郑荣寿, 曾红梅, 等. 中国胃癌流行病学现状. 中国肿瘤临床, 2017, 44(1): 52-58.0.
3. Savage SA, Abnet CC, Haque K, et al. Polymorphisms in interleukin -2, -6, and -10 are not associated with gastric cardia or esophageal cancer in a high-risk Chinese population. Cancer Epidemiol Biomarkers Prev, 2004, 13(9): 1547-1549.
4. Macarthur M, Hold GL, El-Omar EM. Inflammation and cancer II. Role of chronic inflammation and cytokine gene polymorphisms in the pathogenesis of gastrointestinal malignancy. Am J Physiol Gastrointest Liver Physiol, 2004, 286(4): G515-G520.
5. Li K, Xia F, Zhang K, et al. Association of a tgf-b1-509c/t polymorphism with gastric cancer risk: a meta-analysis. Ann Hum Genet, 2013, 77(1): 1-8.
6. Fishman D, Faulds G, Jeffery R, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest, 1998, 102(7): 1369-1376.
7. El-Omar EM, Rabkin CS, Gammon MD, et al. Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology, 2003, 124(5): 1193-1201.
8. Hwang IR, Hsu PI, Peterson LE, Gutierrez O, et al. Interleukin-6 genetic polymorphisms are not related to Helicobacter pylori-associated gastroduodenal diseases. Helicobacter, 2003, 8(2): 142-148.
9. Gatti LL, Burbano RR, Zambaldi-Tunes M, et al. Interleukin-6 polymorphisms, Helicobacter pylori infection in adult Brazilian patients with chronic gastritis and gastric adenocarcinoma. Arch Med Res, 2007, 38(5): 551-555.
10. Kamangar F, Abnet CC, Hutchinson AA, et al. Polymorphisms in inflammation-related genes and risk of gastric cancer (Finland). Cancer Causes Control, 2006, 17(1): 117-125.
11. Deans C, Rose-Zerilli M, Wigmore S, et al. Host cytokine genotype is related to adverse prognosis and systemic inflammation in gastro-oesophageal cancer. Ann Surg Oncol, 2007, 14(2): 329-339.
12. Crusius JB, Canzian F, Capellá G, et al. Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST). Ann Oncol, 2008, 19(11): 1894-1902.
13. 邢培祥, 肖东杰, 曾庆东, 等. 细胞因子基因多态性与胃腺癌发生及其临床病理特点的关系. 中国普通外科杂志, 2006, 15(9): 659-663.0.
14. 赵勇, 肖滢, 高峰, 等. 甘肃武威地区胃癌发病风险与 IL-6 基因多态性的相关性研究. 临床军医杂志, 2010, 38(1): 25-27.0.
15. 王昆龄, 陈凡, 王晓莉. 白细胞介素-6 与胃癌易感性的相关关系. 现代预防医学, 2014, 41(18): 3450-3452.0.
16. 李湘楚, 熊建光, 程正位, 等. 白细胞介素-6 与胃癌易感性的相关研究. 胃肠病学和肝病学杂志, 2014, 23(6): 708-711.0.
17. 曹春莉. IL-6 174G/C 基因多态性与胃肿瘤易感性多因素分析研究. 现代预防医学, 2014, 41(20): 3756-3758, 3783.0.
18. Pohjanen VM, Koivurova OP, Mäkinen JM, et al. Interleukin 6 gene polymorphism -174 is associated with the diffuse type gastric carcinoma. Genes Chromosomes Cancer, 2013, 52(10): 976-982.
19. Sampaio AM, Balseiro SC, Silva MR, et al. Association between IL-4 and IL-6 expression variants and gastric cancer among portuguese population. GE Port J Gastroenterol, 2015, 22(4): 143-152.
20. Guggenheim DE, Shah MA. Gastric cancer epidemiology and risk factors. J Surg Oncol, 2013, 107(3): 230-236.
21. Bonequi P, Meneses-González F, Correa P, et al. Risk factors for gastric cancer in Latin America: a meta-analysis. Cancer Causes Control, 2013, 24(2): 217-231.
22. Testa R, Olivieri F, Bonfigli AR, et al. Interleukin-6-174 G > C polymorphism affects the association between IL-6 plasma levels and insulin resistance in type 2 diabetic patients. Diabetes Res Clin Pract, 2006, 71(3): 299-305.
23. Mandal S, Abebe F, Chaudhary J. -174G/C polymorphism in the interleukin-6 promoter is differently associated with prostate cancer incidence depending on race. Genet Mol Res, 2014, 13(1): 139-151.
24. Kim JM, Stewart R, Kim SY, et al. A one year longitudinal study of cytokine genes and depression in breast cancer. J Affect Disord, 2013, 148(1): 57-65.
25. Peng WJ, He Q, Yang JX, et al. Meta-analysis of association between cytokine gene polymorphisms and lung cancer risk. Mol Biol Rep, 2012, 39(5): 5187-5194.
26. Giannitrapani L, Soresi M, Giacalone A, et al. IL-6 -174G/C polymorphism and IL-6 serum levels in patients with liver cirrhosis and hepatocellular carcinoma. OMICS, 2011, 15(3): 183-186.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Association between –174C/G genetic polymorphism of interleukin-6 and susceptibility to gastric cancer: a meta-analysis

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