Meta-analysis on the Relationship between Methylenetetrahydrofolate Reductase Gene C677T Polymorphism and the Sensitivity to Chemotherapy in Patients with Advanced Gastric Cancer_West China Medical Journal

Authors：

 XUEJin-cai ¹ , WANGQian-qian ² , WANGTao ² , WANGYu-feng ¹ , DINGFang-hui ¹ ,  GUANQuan-lin ³

1. The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730000, P. R. China;
2. Department of Oncology, Tumor Hospital of Gansu Province, Lanzhou, Gansu 730050, P. R. China;
3. Department of Oncological Surgery, the First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P. R. China;

Corresponding author：

GUANQuan-lin, Email: guanquanlin@163.com

Keywords：

Advanced gastric cancer; Methylenetetrahydrofolate reductase gene; Polymorphism; Chemotherapy; Meta-analysis

DOI：

10.7507/1002-0179.20140670

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To evaluate the relationship between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and efficacy of fluorouracil-based chemotherapy in patients with advanced gastric cancer (AGC). Methods Computer retrieval in China Journal Full-text Database, Chinese Science and Technology Periodical Database, Wanfang database, Chinese Biomedical Literature Database, PubMed, EMbase, Cochrane Library and Web of Science Database (from their establishment to May 28, 2013) was performed to include case-control studies on MTHFR gene C677T polymorphism and sensitivity to fluorouracil-based chemotherapy in patients with advanced gastric cancer. Statistical analysis was done by using RevMan 5.1 software. Results Seven case-control studies with 775 patients were included. The meta-analysis showed that among MTHFR C677T genotypes, for TT vs. CC, OR=4.63, 95%CI (1.23, 17.4); and for CC+CT vs. TT, OR=0.21, 95%CI (0.06, 0.78). Subgroup analysis of Asian group showed that for TT vs. CC, OR=32.99, 95%CI (11.40,95.42); and for CC+CT vs. TT, OR=0.04, 95%CI (0.02, 0.10). Sensitivity analysis performed according to different detection methods showed that for TT vs. CC, OR=6.03, 95%CI (1.53, 23.72); and for CC+CT vs.TT, OR=0.17, 95%CI (0.04, 0.68). Conclusion Polymorphism of MTHFR C677T gene may be associated with sensitivity to fluorouracil-based chemotherapy in patients with AGC.

Citation： XUEJin-cai, WANGQian-qian, WANGTao, WANGYu-feng, DINGFang-hui, GUANQuan-lin. Meta-analysis on the Relationship between Methylenetetrahydrofolate Reductase Gene C677T Polymorphism and the Sensitivity to Chemotherapy in Patients with Advanced Gastric Cancer. West China Medical Journal, 2014, 29(12): 2214-2219. doi: 10.7507/1002-0179.20140670 Copy

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18.	Dong XL, Wu J, Liang P, et al. Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer:a meta-analysis[J]. Arch Med Res, 2010, 41(2):125-133.
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20.	Zintzaras E. Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer:a meta-analysis[J]. J Hum Genet, 2006, 51(7):618-624.
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22.	De Mattia E, Toffoli G. C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation[J]. Eur J Cancer, 2009, 45(8):1333-1351.

1. Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90.
2. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008[J]. Int J Cancer, 2010, 127(12):2893-2917.
3. GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research International Collaboration) Group, Paoletti X, Oba K, et al. Benefit of adjuvant chemotherapy for resectable gastric cancer:a meta-analysis[J]. JAMA, 2010, 303(17):1729-1737.
4. Karpeh J. Palliative treatment and the role of surgical resection in gastric cancer[J]. Dig Surg, 2013, 30(2):174-180.
5. Bang YJ, Kim YW, Yang HK, et al. Adjuvant capecitabine auund oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC):a phase 3 open-label, randomised controlled trial[J]. Lancet, 2012, 379(9813):315-321.
6. Goekkurt E, Hoehn S, Wolschke C, et al. Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS):novel predictors for response and survival in gastric cancer patients[J]. Br J Cancer, 2006, 94(2):281-286.
7. 高长明, 陆建伟, Takezaki T, 等. 亚甲基四氢叶酸还原酶基因多态性与胃癌化疗的敏感性关系的研究[J]. 中华流行病学杂志, 2004, 25(12):1054-1058.
8. Ruzzo A, Graziano F, Kawakami K, et al. Pharmacogenetic profiling and clinical outcome of patients with advanced gastric cancer treated with palliative chemotherapy[J]. J Clin Oncol, 2006, 24(12):1883-1891.
9. Ott K, Vogelsang H, Marton N, et al. The thymidylate synthase tandem repeat promoter polymorphism:a predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer[J]. Int J Cancer, 2006, 119(12):2885-2894.
10. Goekkurt E, Al-Batran SE, Hartmann JT, et al. Pharmacogenetic analyses of a phase Ⅲ trial in metastatic gastroesophageal adenocarcinoma with fluorouracil and leucovorin plus either oxaliplatin or cisplatin:a study of the arbeitsgemeinschaft internistische onkologie[J]. J Clin Oncol, 2009, 27(17):2863-2873.
11. 刘德林, 陆建伟, 高长明, 等. MTHFR多态性对晚期胃癌患者化疗作用的预测研究[J]. 中华肿瘤防治杂志, 2006, 13(20):1564-1567.
12. 李洁, 季枚, 吴昌平, 等. 亚甲基四氢叶酸还原酶C667T基因多态性与晚期胃癌患者对5-FU化疗疗效的相关性[J]. 江苏医药, 2010, 36(18):2125-2127.
13. Park SC, Chun HJ. Chemotherapy for advanced gastric cancer:review and update of current practices[J]. Gut Liver, 2013, 7(4):385-393.
14. Longley DB, Harkin DP, Johnston PG. 5-fluorouracil:mechanisms of action and clinical strategies[J]. Nat Rev Cancer, 2003, 3(5):330-338.
15. Oda S, Kuraoka I, Maehara Y. DNA repair as a determinant of tumour chemosensitivity[J]. Gan To Kagaku Ryoho, 2007, 34(3):347-357.
16. Garcia-Aguilar J, Chen Z, Smith DD, et al. Identification of a biomarker profile associated with resistance to neoadjuvant chemoradiation therapy in rectal cancer[J]. Ann Surg, 2011, 254(3):486-492.
17. Sibani S, Leclerc D, Weisberg IS, et al. Characterization of mutations in severe methylenetetrahydrofolate reductase deficiency reveals an FAD-responsive mutation[J]. Hum Mutat, 2003, 21(5):509-520.
18. Dong XL, Wu J, Liang P, et al. Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer:a meta-analysis[J]. Arch Med Res, 2010, 41(2):125-133.
19. Rozen R. Genetic predisposition to hyperhomocysteinemia:deficiency of methylenetetrahydrofolate reductase (MTHFR)[J]. Thromb Haemost, 1997, 78(1):523-526.
20. Zintzaras E. Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer:a meta-analysis[J]. J Hum Genet, 2006, 51(7):618-624.
21. Zintzaras E, Ziogas DC, Kitsios GD, et al. MTHFR gene polymorphisms and response to chemotherapy in colorectal cancer:a meta-analysis[J]. Pharmacogenomics, 2009, 10(8):1285-1294.
22. De Mattia E, Toffoli G. C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation[J]. Eur J Cancer, 2009, 45(8):1333-1351.

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Meta-analysis on the Relationship between Methylenetetrahydrofolate Reductase Gene C677T Polymorphism and the Sensitivity to Chemotherapy in Patients with Advanced Gastric Cancer

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