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Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2006 Mar 14;20(2):37–41. doi: 10.1002/jcla.20103

MTHFR C677 T gene polymorphism in lymphoproliferative diseases

Ugur Deligezer 1, Ebru E Akisik 1, Fulya Yaman 2, Nilgün Erten 3, Nejat Dalay 1,
PMCID: PMC6807388  PMID: 16538645

Abstract

Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, has been implicated in cancer risk. In the present study we used a melting curve analysis to investigate the association of the common MTHFR C677 T polymorphism with lymphoproliferative diseases. Patients (n=117) were compared with age‐ and sex‐matched control subjects (n=154). Our results indicate that the 677 T variant occurred less frequently in patients (26%) than in the control group (33.7%; P=0.05). Investigation of the variant allele (677 T) frequency in the subgroups with Hodgkin's lymphoma (HL) and B‐cell neoplasms (BCNs) revealed that this difference was a result of the significantly lower distribution of the variant allele in patients with HL (20.5%; P=0.01). This was accompanied by a significantly higher frequency of the homozygote normal genotype (677CC) among the patients with HL. In patients with BCNs the distribution of the variant allele (30.3%) was comparable to that in the control group (P=0.47). However, the difference between HL (20.5%) and BCNs (30.3%) did not reach statistical significance (P=0.09). Our results suggest that the distribution of the C677 T polymorphism may vary among lymphoproliferative diseases. J. Clin. Lab. Anal. 20:37–41, 2006. © 2006 Wiley‐Liss, Inc.

Keywords: lymphoproliferative diseases, Hodgkin's lymphoma, B‐cell neoplasms, MTHFR polymorphism, melting curve analysis

REFERENCES

  • 1. Chiu BC, Weisenburger DD. An update of the epidemiology of non‐Hodgkin's lymphomas. Clin Lymphoma 2003;4:161–168. [DOI] [PubMed] [Google Scholar]
  • 2. Fisher SG, Fisher RI. The epidemiology of non‐Hodgkin's lymphoma. Oncogene 2004;23:6524–6534. [DOI] [PubMed] [Google Scholar]
  • 3. Bukowski JA, Huebner WW, Schnatter AR, Wojcik NC. An analysis of the risk of B‐lymphocyte malignancies in industrial cohorts. J Toxicol Environ Health A 2003;66:581–597. [DOI] [PubMed] [Google Scholar]
  • 4. Verhaar MC, Stroes E, Rabelink TJ. Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol 2002;22:6–13. [DOI] [PubMed] [Google Scholar]
  • 5. Kwasniewska A, Tukendorf A, Semczuk M. Folate deficiency and cervical intraepithelial neoplasia. Eur J Gynaecol Oncol 1997;18:526–530. [PubMed] [Google Scholar]
  • 6. Eichholzer M, Luthy J, Moser U, Fowler B. Folate and the risk of colorectal, breast and cervix cancer: the epidemiological evidence. Swiss Med Wkly 2001;131:539–549. [DOI] [PubMed] [Google Scholar]
  • 7. Robien K, Ulrich CM. 5,10‐Methylenetetrahydrofolate reductase polymorphisms and leukemia risk: a HuGE minireview. Am J Epidemiol 2003;157:571–582. [DOI] [PubMed] [Google Scholar]
  • 8. Shellnutt KD, Kauwell GP, Gregory 3rd JF, et al. Methylenetetrahydrofolate reductase 677C → T polymorphism affects DNA methylation in response to controlled folate intake in young women. J Nutr Biochem 2004;15:554–560. [DOI] [PubMed] [Google Scholar]
  • 9. Zingg JM, Jones PA. Genetic and epigenetic aspects of DNA methylation on genome expression, evolution, mutation and carcinogenesis. Carcinogenesis 1997;18:869–882. [DOI] [PubMed] [Google Scholar]
  • 10. Frosst P, Blom HJ, Milos R, et al. Candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Gen 1995;10:111–113. [DOI] [PubMed] [Google Scholar]
  • 11. Jacques PF, Bostom AG, Williams RR, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996;93:7–9. [DOI] [PubMed] [Google Scholar]
  • 12. Kauwell GP, Wilsky CE, Cerda JJ, et al. Methylenetetrahydrofolate reductase mutation (677C → T) negatively influences plasma homocysteine response to marginal folate intake in elderly women. Metabolism 2000;49:1440–1443. [DOI] [PubMed] [Google Scholar]
  • 13. Esteller M, Garcia A, Martinez‐Palones JM, Xercavins J, Reventos J. Germ line polymorphisms in cytochrome‐P450 1A1 (C4887 CYP1A1) and methylenetetrahydrofolate reductase (MTHFR) genes and endometrial cancer susceptibility. Carcinogenesis 1997;18:2307–2311. [DOI] [PubMed] [Google Scholar]
  • 14. Piyathilake CJ, Macaluso M, Johanning GL, Whiteside M, Heimburger DC, Giuliano A. Methylenetetrahydrofolate reductase (MTHFR) polymorphism increases the risk of cervical intraepithelial neoplasia. Anticancer Res 2000;20:1751–1757. [PubMed] [Google Scholar]
  • 15. Siemianowicz K, Gminski J, Garczorz W, et al. Methylenetetrahydrofolate reductase gene C677 T and A1298C polymorphisms in patients with small cell and non‐small cell lung cancer. Oncol Rep 2003;10:1341–1344. [PubMed] [Google Scholar]
  • 16. Shen H, Xu Y, Zheng Y, et al. Polymorphisms of 5,10‐methylenetetrahydrofolate reductase and risk of gastric cancer in aChinese population: a case‐control study. Int J Cancer 2001; 95:332–336. [DOI] [PubMed] [Google Scholar]
  • 17. Gershoni‐Baruch R, Dagan E, Israeli D, Kasinetz L, Kadouri E, Friedman E. Association of the C677 T polymorphism in the MTHFR gene with breast and/or ovarian cancer risk in Jewish women. Eur J Cancer 2000;36:2313–2316. [DOI] [PubMed] [Google Scholar]
  • 18. Chen J, Giovannucci E, Kelsey K, et al. A methylenetetrahydrofolate reductase polymophism and the risk of colorectal cancer. Cancer Res 1996;56:4862–4864. [PubMed] [Google Scholar]
  • 19. Chen J, Giovannucci E, Hunter DJ. MTHFR polymorphism, methylene‐replete diets and the risk of colorectal carcinoma and adenoma among U.S. men and women: an example of gene‐environment interactions in colorectal tumorigenesis. J Nutr 1999;129(2S Suppl):560S–564S. [DOI] [PubMed] [Google Scholar]
  • 20. Gonzalez Ordonez AJ, Fernandez Carreira JM, Fernandez Alvarez CR, et al. Normal frequencies of the C677 T genotypes on the methylenetetrahydrofolate reductase (MTHFR) gene among lymphoproliferative disorders but not in multiple myeloma. Leuk Lymphoma 2000;39:607–612. [DOI] [PubMed] [Google Scholar]
  • 21. Gonzalez‐Fraile MI, Garcia‐Sanz R, Mateous MV, et al. Methylenetetrahydrofolate reductase genotype does not play a role in multiple myeloma pathogenesis. Br J Haematol 2002;117:890–892. [DOI] [PubMed] [Google Scholar]
  • 22. Matsuo K, Suzuki R, Hamajima N, et al. Association between polymorphisms of folate‐ and methionine‐metabolizing enzymes and susceptibility to malignant lymphoma. Blood 2001;97:3205–3209. [DOI] [PubMed] [Google Scholar]
  • 23. Skibola CF, Forrest MS, Coppede F, et al. Polymorphisms and haplotypes in folate metabolizing genes and risk of non‐Hodgkin lymphoma. Blood 2004;104:2155–2162. [DOI] [PubMed] [Google Scholar]
  • 24. Gemmati D, Ongaro A, Scapoli GL, et al. Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non‐Hodgkin's lymphoma in adults. Epidemiol Biomarkers Prev 2004;13:787–794. [PubMed] [Google Scholar]
  • 25. Nakamura S, Aoshima T, Ikeda M, Sekido Y, Shimokata K, Niwa T. Simultaneous detection of methylenetetrahydrofolate reductase gene polymorphisms, C677 T and A1298C, by melting curve analysis with LightCycler. Anal Biochem 2002;306:40–43. [DOI] [PubMed] [Google Scholar]
  • 26. Deligezer U, Akisik E, Dalay N. Genotyping of the MTHFR gene polymorphism, C677 T in patients with leukemia by melting curve analysis. Mol Diagn 2003;7:181–185. [DOI] [PubMed] [Google Scholar]
  • 27. Yanamandra K, Bocchini Jr JA, Thurmon TF. Methylenetetrahydrofolate reductase 677CC normal genotype may protect against multiple myeloma. Br J Haematol 2003;120:1094–1095. [DOI] [PubMed] [Google Scholar]
  • 28. Pileri SA, Dirnhofer S, Went P, et al. Diffuse large B‐cell lymphoma: one or more entities? Present controversies and possible tools for its subclassification. Histopathology 2002;41:482–509. [DOI] [PubMed] [Google Scholar]
  • 29. Hansmann ML, Willenbrock K. WHO classification of Hodgkin's lymphoma and its molecular pathological relevance. Pathologe 2002;23:207–218. [DOI] [PubMed] [Google Scholar]
  • 30. Sharp L, Little J, Schofield AC, et al. Folate and breast cancer: the role of polymorphisms in methylenetetrahydrofolate reductase (MTHFR). Cancer Lett 2002;181:65–71. [DOI] [PubMed] [Google Scholar]
  • 31. Bagley PJ, Selhub J. A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Proc Natl Acad Sci USA 1998;95:13217–13220. [DOI] [PMC free article] [PubMed] [Google Scholar]

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