Association between MTHFR C677T polymorphism and gastric cancer in Chinese population: a meta-analysis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Jiankai ¹ , CAI Hongyi ¹ , MOU Guoying ¹ , ZHANG Lijuan ¹ , MA Wen ¹ , HU Yongguo ¹ , FENG Shifang ¹ ,  WANG Wenjuan ²

1. Department of Radiotherapy, Gansu Provincial People’s Hospital, Lanzhou 730000, P.R.China;
2. Medical Examination Center, The Third People’s Hospital of Gansu Province, Lanzhou 730000, P.R.China;

Corresponding author：

WANG Wenjuan, Email: 15339866618@163.com

Keywords：

gastric cancer; MTHFR; genetic polymorphism; meta-analysis

DOI：

10.7507/1007-9424.201611012

Video：

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Objective To assess the association between MTHFR C677T polymorphism and gastric cancer in Chinese population. Methods Relevant literatures were searched from PubMed, EMBASE, Web of Science, China Biology Medicine Database, Chinese Science and Technology Academic Journal, Chinese Journal Full-Text Database, and Wanfang database, the period ranged from their inception to June 2016, and then meta analysis was performed by Stata 10.0 software. Results A meta-analysis of 13 case-control studies enrolled was performed, including 2 569 gastric cancer patients and 3 495 controls. Results of meta-analysis showed that, in Chinese population, CC was a protective factor for gastric cancer comparing with CT 〔OR=0.75, 95% CI is (0.67, 0.85), P=0.001〕 , CT was a protective factor for gastric cancer comparing with TT 〔OR=0.77, 95% CI is (0.68, 0.89), P=0.001〕 , CC was a protective factor for gastric cancer comparing with TT 〔OR=0.56, 95% CI is (0.49, 0.65), P=0.02〕 , CC was a protective factor for gastric cancer comparing with CT+TT 〔OR=0.68, 95% CI is (0.61, 0.76), P=0.001〕 , CC+CT was a protective factor for gastric cancer comparing with TT 〔OR=0.73, 95% CI is (0.60, 0.89), P=0.002〕 . Conclusion There is association between MTHFR C677T polymorphism and gastric cancer in Chinese population.

Citation： WANG Jiankai, CAI Hongyi, MOU Guoying, ZHANG Lijuan, MA Wen, HU Yongguo, FENG Shifang, WANG Wenjuan. Association between MTHFR C677T polymorphism and gastric cancer in Chinese population: a meta-analysis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(6): 701-709. doi: 10.7507/1007-9424.201611012 Copy

1.	Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
2.	Park JH, Ryu MH, Kim HJ, et al. Risk factors for selection of patients at high risk of recurrence or death after complete surgical resection in stageⅠgastric cancer. Gastric Cancer, 2016, 19(1): 226-233.
3.	González CA, López-Carrillo L. Helicobacter pylori, nutrition and smoking interactions: their impact in gastric carcinogenesis. Scand J Gastroenterol, 2010, 45(1): 6-14.
4.	Song NM, Jun S, Zang DY, et al. Differential susceptibility of gastric cancer cells to TRAIL-induced apoptosis. Oncol Rep, 2013, 29(3): 1224-1230.
5.	Hosseini-Asl SS, Pourfarzi F, Barzegar A, et al. Decrease in gastric cancer susceptibility by MTHFR C677T polymorphism in Ardabil Province, Iran. Turk J Gastroenterol, 2013, 24(2): 117-121.
6.	Ji M, Xu B, Jiang JT, et al. Relationship between glutathione S-transferase P1 (GSTP1), X-ray repair cross complementing group 1 (XRCC1) and 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) gene polymorphisms and response to chemotherapy in advanced gastric cancer. Onkologie, 2013, 36(6): 335-340.
7.	Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet, 1995, 10(1): 111-113.
8.	Wang Y, Guo W, He Y, et al. Association of MTHFR C677T and SHMT(1) C1420T with susceptibility to ESCC and GCA in a high incident region of Northern China. Cancer Causes Control, 2007, 18(2): 143-152.
9.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
10.	Shen H, Xu Y, Zheng Y, et al. Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: a case-control study. Int J Cancer, 2001, 95(5): 332-336.
11.	高长明, 吴建中, 丁建华, 等. 亚甲基四氢叶酸还原酶基因 C677T 多态性与胃癌易感性的关系. 中华流行病学杂志, 2002, 23(4): 289-292.
12.	Miao X, Xing D, Tan W, et al. Susceptibility to gastric cardia adenocarcinoma and genetic polymorphisms in methylenetetrahydrofolate reductase in an at-risk Chinese population. Cancer Epidemiol Biomarkers Prev, 2002, 11(11): 1454-1458.
13.	司佩任, 房殿春, 张浩, 等. 亚甲基四氢叶酸还原酶基因多态性与胃癌关系的研究. 重庆医学, 2003, 32(9): 1123-1125.
14.	穆丽娜, 丁保国, 陈传炜, 等. 亚甲基四氢叶酸还原酶 677 基因多态性与胃癌危险度关系病例对照研究. 中华流行病学杂志, 2004, 25(6): 495-498.
15.	Shen H, Newmann AS, Hu Z, et al. Methylenetetrahydrofolate reductase polymorphisms/haplotypes and risk of gastric cancer: a case-control analysis in China. Oncol Rep, 2005, 13(2): 355-360.
16.	毕建萍, 蔡琳, 郑宗立. 亚甲基四氢叶酸还原酶基因多态与胃癌易感性. 中国公共卫生, 2005, 21(6): 661-663.
17.	李松, 祭美菊, 侯鹏, 等. 亚甲基四氢叶酸还原酶基因 C677T 和 A1298C 多态与胃癌的遗传易感性. 东南大学学报(医学版), 2006, 25(5): 321-324.
18.	翁玉蓉, 房静远, 孙丹凤, 等. 胃癌组织中叶酸水平与代谢酶亚甲基四氢叶酸还原酶基因多态性的关系研究. 中华消化杂志, 2006, 26(1): 26-30.
19.	杨学习, 李粉霞, 易金萍, 等. 亚甲基四氢叶酸还原酶基因 C677T 多态性与胃癌、大肠癌和肺癌易感性的关系. 广东医学, 2010, 31(18): 2375-2378.
20.	郭威, 陈萍, 郑立红, 等. MTHFR 基因多态性与胃癌的相关性. 世界华人消化杂志, 2012, 376(8): 690-693.
21.	Gao S, Ding LH, Wang JW, et al. Diet folate, DNA methylation and polymorphisms in methylenetetrahydrofolate reductase in association with the susceptibility to gastric cancer. Asian Pac J Cancer Prev, 2013, 14(1): 299-302.
22.	Xia J, Han L, Zhao Z. Investigating the relationship of DNA methylation with mutation rate and allele frequency in the human genome. BMC Genomics, 2012, 13 Suppl 8: S7.
23.	Kim JG, Takeshima H, Niwa T, et al. Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers. Cancer Lett, 2013, 330(1): 33-40.
24.	Stern LL, Mason JB, Selhub J, et al. Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene. Cancer Epidemiol Biomarkers Prev, 2000, 9(8): 849-853.
25.	Graziano F, Kawakami K, Ruzzo A, et al. Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian population. Int J Cancer, 2006, 118(3): 628-632.
26.	Gonda TA, Kim YI, Salas MC, et al. Folic acid increases global DNA methylation and reduces inflammation to prevent Helicobacter-associated gastric cancer in mice. Gastroenterology, 2012, 142(4): 824-833.
27.	Larsson SC, Giovannucci E, Wolk A. Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology, 2006, 131(4): 1271-1283.
28.	Ulvik A, Ueland PM, Fredriksen A, et al. Functional inference of the methylenetetrahydrofolate reductase 677C>T and 1298A>C polymorphisms from a large-scale epidemiological study. Hum Genet, 2007, 121(1): 57-64.
29.	Zacho J, Yazdanyar S, Bojesen SE, et al. Hyperhomocysteinemia, methylenetetrahydrofolate reductase c. 677C>T polymorphism and risk of cancer: cross-sectional and prospective studies and meta-analyses of 75,000 cases and 93,000 controls. Int J Cancer, 2011, 128(3): 644-652.

1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
2. Park JH, Ryu MH, Kim HJ, et al. Risk factors for selection of patients at high risk of recurrence or death after complete surgical resection in stageⅠgastric cancer. Gastric Cancer, 2016, 19(1): 226-233.
3. González CA, López-Carrillo L. Helicobacter pylori, nutrition and smoking interactions: their impact in gastric carcinogenesis. Scand J Gastroenterol, 2010, 45(1): 6-14.
4. Song NM, Jun S, Zang DY, et al. Differential susceptibility of gastric cancer cells to TRAIL-induced apoptosis. Oncol Rep, 2013, 29(3): 1224-1230.
5. Hosseini-Asl SS, Pourfarzi F, Barzegar A, et al. Decrease in gastric cancer susceptibility by MTHFR C677T polymorphism in Ardabil Province, Iran. Turk J Gastroenterol, 2013, 24(2): 117-121.
6. Ji M, Xu B, Jiang JT, et al. Relationship between glutathione S-transferase P1 (GSTP1), X-ray repair cross complementing group 1 (XRCC1) and 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) gene polymorphisms and response to chemotherapy in advanced gastric cancer. Onkologie, 2013, 36(6): 335-340.
7. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet, 1995, 10(1): 111-113.
8. Wang Y, Guo W, He Y, et al. Association of MTHFR C677T and SHMT(1) C1420T with susceptibility to ESCC and GCA in a high incident region of Northern China. Cancer Causes Control, 2007, 18(2): 143-152.
9. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
10. Shen H, Xu Y, Zheng Y, et al. Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: a case-control study. Int J Cancer, 2001, 95(5): 332-336.
11. 高长明, 吴建中, 丁建华, 等. 亚甲基四氢叶酸还原酶基因 C677T 多态性与胃癌易感性的关系. 中华流行病学杂志, 2002, 23(4): 289-292.
12. Miao X, Xing D, Tan W, et al. Susceptibility to gastric cardia adenocarcinoma and genetic polymorphisms in methylenetetrahydrofolate reductase in an at-risk Chinese population. Cancer Epidemiol Biomarkers Prev, 2002, 11(11): 1454-1458.
13. 司佩任, 房殿春, 张浩, 等. 亚甲基四氢叶酸还原酶基因多态性与胃癌关系的研究. 重庆医学, 2003, 32(9): 1123-1125.
14. 穆丽娜, 丁保国, 陈传炜, 等. 亚甲基四氢叶酸还原酶 677 基因多态性与胃癌危险度关系病例对照研究. 中华流行病学杂志, 2004, 25(6): 495-498.
15. Shen H, Newmann AS, Hu Z, et al. Methylenetetrahydrofolate reductase polymorphisms/haplotypes and risk of gastric cancer: a case-control analysis in China. Oncol Rep, 2005, 13(2): 355-360.
16. 毕建萍, 蔡琳, 郑宗立. 亚甲基四氢叶酸还原酶基因多态与胃癌易感性. 中国公共卫生, 2005, 21(6): 661-663.
17. 李松, 祭美菊, 侯鹏, 等. 亚甲基四氢叶酸还原酶基因 C677T 和 A1298C 多态与胃癌的遗传易感性. 东南大学学报(医学版), 2006, 25(5): 321-324.
18. 翁玉蓉, 房静远, 孙丹凤, 等. 胃癌组织中叶酸水平与代谢酶亚甲基四氢叶酸还原酶基因多态性的关系研究. 中华消化杂志, 2006, 26(1): 26-30.
19. 杨学习, 李粉霞, 易金萍, 等. 亚甲基四氢叶酸还原酶基因 C677T 多态性与胃癌、大肠癌和肺癌易感性的关系. 广东医学, 2010, 31(18): 2375-2378.
20. 郭威, 陈萍, 郑立红, 等. MTHFR 基因多态性与胃癌的相关性. 世界华人消化杂志, 2012, 376(8): 690-693.
21. Gao S, Ding LH, Wang JW, et al. Diet folate, DNA methylation and polymorphisms in methylenetetrahydrofolate reductase in association with the susceptibility to gastric cancer. Asian Pac J Cancer Prev, 2013, 14(1): 299-302.
22. Xia J, Han L, Zhao Z. Investigating the relationship of DNA methylation with mutation rate and allele frequency in the human genome. BMC Genomics, 2012, 13 Suppl 8: S7.
23. Kim JG, Takeshima H, Niwa T, et al. Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers. Cancer Lett, 2013, 330(1): 33-40.
24. Stern LL, Mason JB, Selhub J, et al. Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene. Cancer Epidemiol Biomarkers Prev, 2000, 9(8): 849-853.
25. Graziano F, Kawakami K, Ruzzo A, et al. Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian population. Int J Cancer, 2006, 118(3): 628-632.
26. Gonda TA, Kim YI, Salas MC, et al. Folic acid increases global DNA methylation and reduces inflammation to prevent Helicobacter-associated gastric cancer in mice. Gastroenterology, 2012, 142(4): 824-833.
27. Larsson SC, Giovannucci E, Wolk A. Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology, 2006, 131(4): 1271-1283.
28. Ulvik A, Ueland PM, Fredriksen A, et al. Functional inference of the methylenetetrahydrofolate reductase 677C>T and 1298A>C polymorphisms from a large-scale epidemiological study. Hum Genet, 2007, 121(1): 57-64.
29. Zacho J, Yazdanyar S, Bojesen SE, et al. Hyperhomocysteinemia, methylenetetrahydrofolate reductase c. 677C>T polymorphism and risk of cancer: cross-sectional and prospective studies and meta-analyses of 75,000 cases and 93,000 controls. Int J Cancer, 2011, 128(3): 644-652.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Association between MTHFR C677T polymorphism and gastric cancer in Chinese population: a meta-analysis

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