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.	高長明, 吳建中, 丁建華, 等. 亞甲基四氫葉酸還原酶基因 C677T 多態性與胃癌易感性的關系. 中華流行病學雜志, 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, 張浩, 等. 亞甲基四氫葉酸還原酶基因多態性與胃癌關系的研究. 重慶醫學, 2003, 32(9): 1123-1125.
14.	穆麗娜, 丁保國, 陳傳煒, 等. 亞甲基四氫葉酸還原酶 677 基因多態性與胃癌危險度關系病例對照研究. 中華流行病學雜志, 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.	畢建萍, 蔡琳, 鄭宗立. 亞甲基四氫葉酸還原酶基因多態與胃癌易感性. 中國公共衛生, 2005, 21(6): 661-663.
17.	李松, 祭美菊, 侯鵬, 等. 亞甲基四氫葉酸還原酶基因 C677T 和 A1298C 多態與胃癌的遺傳易感性. 東南大學學報(醫學版), 2006, 25(5): 321-324.
18.	翁玉蓉, 房靜遠, 孫丹鳳, 等. 胃癌組織中葉酸水平與代謝酶亞甲基四氫葉酸還原酶基因多態性的關系研究. 中華消化雜志, 2006, 26(1): 26-30.
19.	楊學習, 李粉霞, 易金萍, 等. 亞甲基四氫葉酸還原酶基因 C677T 多態性與胃癌、大腸癌和肺癌易感性的關系. 廣東醫學, 2010, 31(18): 2375-2378.
20.	郭威, 陳萍, 鄭立紅, 等. MTHFR 基因多態性與胃癌的相關性. 世界華人消化雜志, 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. 高長明, 吳建中, 丁建華, 等. 亞甲基四氫葉酸還原酶基因 C677T 多態性與胃癌易感性的關系. 中華流行病學雜志, 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, 張浩, 等. 亞甲基四氫葉酸還原酶基因多態性與胃癌關系的研究. 重慶醫學, 2003, 32(9): 1123-1125.
14. 穆麗娜, 丁保國, 陳傳煒, 等. 亞甲基四氫葉酸還原酶 677 基因多態性與胃癌危險度關系病例對照研究. 中華流行病學雜志, 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. 畢建萍, 蔡琳, 鄭宗立. 亞甲基四氫葉酸還原酶基因多態與胃癌易感性. 中國公共衛生, 2005, 21(6): 661-663.
17. 李松, 祭美菊, 侯鵬, 等. 亞甲基四氫葉酸還原酶基因 C677T 和 A1298C 多態與胃癌的遺傳易感性. 東南大學學報(醫學版), 2006, 25(5): 321-324.
18. 翁玉蓉, 房靜遠, 孫丹鳳, 等. 胃癌組織中葉酸水平與代謝酶亞甲基四氫葉酸還原酶基因多態性的關系研究. 中華消化雜志, 2006, 26(1): 26-30.
19. 楊學習, 李粉霞, 易金萍, 等. 亞甲基四氫葉酸還原酶基因 C677T 多態性與胃癌、大腸癌和肺癌易感性的關系. 廣東醫學, 2010, 31(18): 2375-2378.
20. 郭威, 陳萍, 鄭立紅, 等. MTHFR 基因多態性與胃癌的相關性. 世界華人消化雜志, 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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