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Association of MTHFR C677T and SHMT1 C1420T with susceptibility to ESCC and GCA in a high incident region of Northern China

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Abstract

Objective

To assess the association between the C to T transition in the methylenetetrahydro folate reductase gene (MTHFR C677T) and the C to T transition in the serine hydroxymethyltransferase 1 gene (SHMT 1 C1420T) and the increased risk of carcinogenesis of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in a population of high incident region of Northern China.

Methods

The polymorphisms were genotyped by polymerase chain reaction–restriction fragment length polymorphism and PCR-confronting two-pair primers analysis respectively among 1051 cancer patients (584 ESCC and 467 GCA) and 540 healthy controls.

Results

The MTHFR 677T/T genotype significantly increased susceptibility to both ESCC and GCA compared with the C/C genotype, the adjusted OR was 2.13 (95% CI = 1.50–3.02) and 1.28 (95% CI = 1.07–1.53, respectively. For the SHMT 1 C1420T polymorphism, the C/C genotype was significantly associated with the increased risk of ESCC and GCA, compared with the C/T genotype (the adjusted OR = 1.43 and 1.35, 95% CI = 1.02–2.00 and 1.11–1.63, respectively). The interactive influence of the MTHFR and SHMT 1 polymorphisms in the risk of ESCC and GCA was also observed.

Conclusion

The association between the MTHFR C677T and SHMT 1 C1420T polymorphisms and the risk of ESCC and GCA was demonstrated.

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References

  1. Steinmetz KA, Potter JD (1996) Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc 96:1027–1039

    Article  PubMed  CAS  Google Scholar 

  2. Tseng M, Murray SC, Kupper LL, Sandler RS (1996) Micronutrients and the risk of colorectal adenomas. Am J Epidemiol 144:1005–1014

    PubMed  CAS  Google Scholar 

  3. Choi SW, Mason JB (2000) Folate and carcinogenesis: an integrated scheme. J Nutr 130:129–132

    PubMed  CAS  Google Scholar 

  4. Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, Rozen R (1994) Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet 7:195–200

    Article  PubMed  CAS  Google Scholar 

  5. Bailey LB, Gregory JF 3rd (1999) Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr 129:919–922

    PubMed  CAS  Google Scholar 

  6. Frosst P, Blom HJ, Milos R et al. (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113

    Article  PubMed  CAS  Google Scholar 

  7. Saffroy R, Pham P, Chiappini F et al. (2004) The MTHFR 677C > T polymorphism is associated with an increased risk of hepatocellular carcinoma in patients with alcoholic cirrhosis. Carcinogenesis 25:1443–1448

    Article  PubMed  CAS  Google Scholar 

  8. Lin J, Spitz MR, Wang Y et al. (2004) Polymorphisms of folate metabolic genes and susceptibility to bladder cancer: a case–control study. Carcinogenesis 25:1639–1647

    Article  PubMed  CAS  Google Scholar 

  9. Yang CX, Matsuo K, Ito H et al. (2005) Gene–environment interactions between alcohol drinking and the MTHFR C677T polymorphism impact on esophageal cancer risk: results of a case–control study in Japan. Carcinogenesis 26:1285–1290

    Article  PubMed  CAS  Google Scholar 

  10. Matsuo K, Ito H, Wakai K et al. (2005) One-carbon metabolism related gene polymorphisms interact with alcohol drinking to influence the risk of colorectal cancer in Japan. Carcinogenesis (Epub ahead of print)

  11. Girgis S, Suh JR, Jolivet J, Stover PJ (1997) 5-Formyltetrahydrofolate regulates homocysteine remethylation in human neuroblastoma. J Biol Chem 272:4729–4734

    Article  PubMed  CAS  Google Scholar 

  12. Schirch L, Peterson D (1980) Purification and properties of mitochondrial serine hydroxymethyltransferase. J Biol Chem 255:7801–7806

    PubMed  CAS  Google Scholar 

  13. van der Put NM, van der Molen EF, Kluijtmans LA et al. (1997) Sequence analysis of the coding region of human methionine synthase: relevance to hyperhomocysteinaemia in neural-tube defects and vascular disease. Qjm 90:511–517

    Article  PubMed  Google Scholar 

  14. Hishida A, Matsuo K, Hamajima N et al. (2003) Associations between polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and susceptibility to malignant lymphoma. Haematologica 88:159–166

    PubMed  CAS  Google Scholar 

  15. Skibola CF, Smith MT, Hubbard A et al. (2002) Polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and risk of adult acute lymphocytic leukemia. Blood 99:3786–3791

    Article  PubMed  CAS  Google Scholar 

  16. Song C, Xing D, Tan W, Wei Q, Lin D (2001) Methylenetetrahydrofolate reductase polymorphisms increase risk of esophageal squamous cell carcinoma in a Chinese population. Cancer Res 61:3272–3275

    PubMed  CAS  Google Scholar 

  17. Miao X, Xing D, Tan W, Qi J, Lu W, Lin D (2002) Susceptibility to gastric cardia adenocarcinoma and genetic polymorphisms in methylenetetrahydrofolate reductase in an at-risk Chinese population. Cancer Epidemiol Biomarkers Prev 11:1454–1458

    PubMed  CAS  Google Scholar 

  18. Zhang J, Zotz RB, Li Y et al. (2004) Methylenetetrahydrofolate reductase C677T polymorphism and predisposition towards esophageal squamous cell carcinoma in a German Caucasian and a northern Chinese population. J Cancer Res Clin Oncol 130:574–580

    PubMed  CAS  Google Scholar 

  19. Tan W, Miao X, Wang L et al. (2005) Significant increase in risk of gastroesophageal cancer is associated with interaction between promoter polymorphisms in thymidylate synthase and serum folate status. Carcinogenesis 26:1430–1435

    Article  PubMed  CAS  Google Scholar 

  20. Zhang J, Cui Y, Kuang G et al. (2004) Association of the thymidylate synthase polymorphisms with esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma. Carcinogenesis 25:2479–2485

    Article  PubMed  CAS  Google Scholar 

  21. Sarbia M, Stahl M, von Weyhern C, Weirich G, Puhringer-Oppermann F (2006) The prognostic significance of genetic polymorphisms (Methylenetetrahydrofolate Reductase C677T, Methionine Synthase A2756G, Thymidilate Synthase tandem repeat polymorphism) in multimodally treated oesophageal squamous cell carcinoma. Br J Cancer 94:203–207

    Article  PubMed  CAS  Google Scholar 

  22. Yang CX, Matsuo K, Ito H et al. (2005) Gene–environment interactions between alcohol drinking and the MTHFR C677T polymorphism impact on esophageal cancer risk: results of a case–control study in Japan. Carcinogenesis 26:1285–1290

    Article  PubMed  CAS  Google Scholar 

  23. Stolzenberg-Solomon RZ, Qiao YL, Abnet CC et al. (2003) Esophageal and gastric cardia cancer risk and folate- and vitamin B(12)-related polymorphisms in Linxian, China. Cancer Epidemiol Biomarkers Prev 12:1222–1226

    PubMed  CAS  Google Scholar 

  24. Wang LD, Guo RF, Fan ZM et al. (2005) Association of methylenetetrahydrofolate reductase and thymidylate synthase promoter polymorphisms with genetic susceptibility to esophageal and cardia cancer in a Chinese high-risk population. Dis Esophagus 18:177–184

    Article  PubMed  Google Scholar 

  25. Shen H, Newmann AS, Hu Z et al. (2005) Methylenetetrahydrofolate reductase polymorphisms/haplotypes and risk of gastric cancer: a case–control analysis in China. Oncol Rep 13:355–360

    PubMed  CAS  Google Scholar 

  26. Miao X, Xing D, Tan W, Lu W, Lin D (2002) Single nucleotide polymorphisms in methylenetetrahydrofolate reductase gene and susceptibility to cancer of the gastric cardia in Chinese population. Zhonghua Yi Xue Za Zhi, 82:669–672

    PubMed  CAS  Google Scholar 

  27. Shen H, Xu Y, Zheng Y et al. (2001) Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: a case–control study. Int J Cancer 95:332–336

    Article  PubMed  CAS  Google Scholar 

  28. Chen J, Kyte C, Valcin M et al. (2004) Polymorphisms in the one-carbon metabolic pathway, plasma folate levels and colorectal cancer in a prospective study. Int J Cancer 110:617–620

    Article  PubMed  CAS  Google Scholar 

  29. Siewert JR, Stein HJ (1998) Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg 85:1457–1459

    Article  PubMed  CAS  Google Scholar 

  30. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucl Acids Res 16:1215

    Article  PubMed  CAS  Google Scholar 

  31. Skibola CF, Smith MT, Kane E et al. (1999) Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. Proc Natl Acad Sci USA 96:12810–12815

    Article  PubMed  CAS  Google Scholar 

  32. Hamajima N, Saito T, Matsuo K, Kozaki K, Takahashi T, Tajima K (2000) Polymerase chain reaction with confronting two-pair primers for polymorphism genotyping. Jpn J Cancer Res 91:865–868

    PubMed  CAS  Google Scholar 

  33. Zhang J, Jin X, Fang S et al. (2004) The functional SNP in the matrix metalloproteinase-3 promoter modifies susceptibility and lymphatic metastasis in esophageal squamous cell carcinoma but not in gastric cardiac adenocarcinoma. Carcinogenesis 25:2519–2524

    Article  PubMed  CAS  Google Scholar 

  34. Girgis S, Nasrallah IM, Suh JR et al. (1998) Molecular cloning, characterization and alternative splicing of the human cytoplasmic serine hydroxymethyltransferase gene. Gene 210:315–324

    Article  PubMed  CAS  Google Scholar 

  35. Piyathilake CJ, Macaluso M, Hine RJ, Richards EW, Krumdieck CL (1994) Local and systemic effects of cigarette smoking on folate and vitamin B-12. Am J Clin Nutr, 60:559–566

    PubMed  CAS  Google Scholar 

  36. Wei Q, Shen H, Wang LE et al. (2003) Association between low dietary folate intake and suboptimal cellular DNA repair capacity. Cancer Epidemiol Biomarkers Prev 12:963–969

    PubMed  CAS  Google Scholar 

  37. Mannino DM, Mulinare J, Ford ES, Schwartz J (2003) Tobacco smoke exposure and decreased serum and red blood cell folate levels: data from the Third National Health and Nutrition Examination Survey. Nicotine Tob Res 5:357–362

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We greatly acknowledge Mrs. Liwei Zhang, Mrs. Xiaoqing Guo, Mr. Qingwen Cong, and Mr. Mingli Wu in the Fourth Affiliated Hospital of Hebei Medical University, China, for their assistance in recruiting study subjects.

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Correspondence to Jianhui Zhang.

Additional information

Yimin Wang, Wei Guo and Yutong He contributed equally to this work. Supported by Grants from the National Natural Science Foundation (No. 30371591), National High Technique Research and Development Project (No. 2002BA711A08), and Natural Science Foundation of Hebei Province (No. C0400062).

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Wang, Y., Guo, W., He, Y. et al. Association of MTHFR C677T and SHMT1 C1420T with susceptibility to ESCC and GCA in a high incident region of Northern China. Cancer Causes Control 18, 143–152 (2007). https://doi.org/10.1007/s10552-006-0097-4

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  • DOI: https://doi.org/10.1007/s10552-006-0097-4

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