FOLATE-METABOLIZING GENES IN DIFFUSE LARGE B-CELL LYMPHOMA
Abstract
Single nucleotide polymorphisms (SNPs) in folate-metabolising genes lead to a decrease in the activity and stability of the corresponding enzymes and can disrupt the functioning of the epigenetic regulation system, which leads to aberrant nucleic acid methylation and, as a result, oncogenesis and tumor progression initiation. The studies of SNPs in selected variants of diffuse large B-cell lymphoma (DLBCL) are rare. In the present study we investigated the role of SNPs in folate-metabolising genes (rs1801133 and rs1801131 MTHFR, rs1805087 MTR, rs1801394 MTRR, rs2236225 MTHFD1, rs1979277 SHMT1) in susceptibility to the immunoblastic variant of DLBCL. Rs1801133 and rs1801131 MTHFR, rs1805087 MTR, rs1801394 MTRR, rs1979277 SHMT1 are not associated with the risk of DLBCL. The wild G allele of the rs2236225 MTHFD1 is associated with an increase (OR = 2.3 CI [1.517-3.584, p <0.0008), and the rare A allele is associated with a reduced risk of an immunoblastic DLBCL (OR = 0.429 CI [0.279-0.659], p <0.0008). The rs2236225 MTHFD1 gene requires further study in patients with DLBCL.
References
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http://www.medlit.ru/journal/857
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http://www.medlit.ru/journalsview/haemathology/view/journal/2016/issue-3/
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http://www.hematology.ru/oncohematology/standarts/clinical_guidelines-draft.pdf
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6. Christensen K.E., Deng L., Bahous R.H. MTHFD1 formyltetrahydrofolate synthetase deficiency, a model for the MTHFD1 R653Q variant, leads to congenital heart defects in mice // Birth Defects Res A Clin Mol Teratol. – 2015. – Vol. 103. № 12. – P. 1031-1038.
https://www.ncbi.nlm.nih.gov/pubmed/?term=26408344
7. Esteller M. Relevance of DNA methylation in the management of cancer // Lancet Oncol. – 2003. – № 4. – Р. 351–358.
https://www.ncbi.nlm.nih.gov/pubmed/?term=12788407
8. Galm O., Herman J.G., Baylin S.B. The fundamental role of epigenetics in hematopoietic malignancies // Blood Rev. – 2006. – Vol. 20. № 1. – Р. 1–13.
https://www.ncbi.nlm.nih.gov/pubmed/16426940
9. Koutros S., Zhang Y., Zhu Y. et al. Nutrients contributing to one-carbon metabolism and risk of non-Hodgkin lymphoma subtypes // American Journal of Epidemiology. – 2008. – Vol. 167. № 3. – P. 287 – 294.
https://academic.oup.com/aje/article/167/3/287/132137
10. Liu H., Jin G., Wang H. et al. Association of polymorphisms in one-carbon metabolizing genes and lung cancer risk: a case-control study in Chinese population // Lung Cancer. – 2008. – Vol. 61. №1. – P. 21-29.
https://www.ncbi.nlm.nih.gov/pubmed/?term=18221821
11. Nogai H., Dörken B., Lenz G. Pathogenesis of non-Hodgkin’s lymphoma // J. Clin. Oncol. – 2011. – № 29. – Р. 1803–1811.
http://ascopubs.org/doi/full/10.1200/JCO.2010.33.3252
12. Shaknovich R., Melnick A. Epigenetics and B-cell lymphoma // Curr. Opin. Hematol.– 2011. – Vol. 18. №4. – P. 293-299.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260081/
13. Skibola C.F., Bracci P.M., Nieters A. Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium // Am J Epidemiol. – 2010. – Vol.171. № 3. – P. 267-276.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842204/pdf/kwp383.pdf
14. Swerdlow S.H. Campo E., Harris N.L. et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues // (Revised 4th edition). IARC: Lyon 2017.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842204/
15. Voropaeva E.N., Voevoda M.I., Maksimov V.N. et al. Prognostic impact of the TP53 rs1625895 polymorphism in DLBCL patients // British Journal of Haematology. – 2015. – Vol. 169. № 1. – P. 32-35.
https://www.ncbi.nlm.nih.gov/pubmed/?term=25430047
16. Weiner A.S., Beresina O.V., Voronina E.N., et al. Polymorphisms in folate-metabolizing genes and risk of non-hodgkin's lymphoma // Leukemia Research. – 2011. – Vol. 35. № 4. – P. 508-515.
https://www.ncbi.nlm.nih.gov/pubmed/21055808
17. Weiner A.S., Gordeeva L.A., Voronina E.N. et al. Polymorphisms in folate-metabolizing genes and risk of having an offspring with congenital anomalies in the West Siberian region of Russia: a case-control study // Prenat. Diagn. – 2012. – Vol. 32. № 11. – P. 1041-1048.
https://www.ncbi.nlm.nih.gov/pubmed/?term=22855024
References
1. Berezina O.V., Pospelova T.I., Ovchinnikov V.S. et al. Glutathione-S-transferase m1 and t1 polymorphism (GSTM1 and GSTT1) in patients with non-Hodgkin's malignant lymphomas // Siberian Scientific Medical Journal. – 2013. – V. 33. №1. – P. 40-46.
http://sibmed.net/article.php?lang=rus&id_article=178
2. Voropaeva E.N., Pospelova T.I., Voevoda M.I. The association of Arg399Gln polymorphism of the XRCC1 DNA repair gene with a risk of developing non-Hodgkin's lymphomas of a high degree of malignancy // Hematology and Transfusiology. –2013. – V. 58. №1. – P. 10-14.
http://www.medlit.ru/journal/857
3. Voropaeva E.N., Pospelova T.I., Voevoda M.I., Maksimov V.N. The results of a comprehensive analysis of the status of the TP53 gene in patients with diffuse large B-cell lymphoma // Hematology and Transfusiology. – 2016. – V. 61. № 3. – P. 138-143.
http://www.medlit.ru/journalsview/haemathology/view/journal/2016/issue-3/
4. Poddubnaya I.V., Savchenko V.G. Russian clinical guidelines for the diagnosis and treatment of lymphoproliferative diseases // Publishing LLC «Buki-Vedi». – 2016. – Moscow, 324 p.
http://www.hematology.ru/oncohematology/standarts/clinical_guidelines-draft.pdf
5. Cerhan J.R., Berndt S.I., Vijai J., Ghesquières H. et al. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma // Nat Genet. – Vol.46. № 11. – P. 1233-1238.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213349/
6. Christensen K.E., Deng L., Bahous R.H. MTHFD1 formyltetrahydrofolate synthetase deficiency, a model for the MTHFD1 R653Q variant, leads to congenital heart defects in mice // Birth Defects Res A Clin Mol Teratol. – 2015. – Vol. 103. № 12. – P. 1031-1038.
https://www.ncbi.nlm.nih.gov/pubmed/?term=26408344
7. Esteller M. Relevance of DNA methylation in the management of cancer // Lancet Oncol. – 2003. – № 4. – Р. 351–358.
https://www.ncbi.nlm.nih.gov/pubmed/?term=12788407
8. Galm O., Herman J.G., Baylin S.B. The fundamental role of epigenetics in hematopoietic malignancies // Blood Rev. – 2006. – Vol. 20. № 1. – Р. 1–13.
https://www.ncbi.nlm.nih.gov/pubmed/16426940
9. Koutros S., Zhang Y., Zhu Y. et al. Nutrients contributing to one-carbon metabolism and risk of non-Hodgkin lymphoma subtypes // American Journal of Epidemiology. – 2008. – Vol. 167. № 3. – P. 287 – 294.
https://academic.oup.com/aje/article/167/3/287/132137
10. Liu H., Jin G., Wang H. et al. Association of polymorphisms in one-carbon metabolizing genes and lung cancer risk: a case-control study in Chinese population // Lung Cancer. – 2008. – Vol. 61. №1. – P. 21-29.
https://www.ncbi.nlm.nih.gov/pubmed/?term=18221821
11. Nogai H., Dörken B., Lenz G. Pathogenesis of non-Hodgkin’s lymphoma // J. Clin. Oncol. – 2011. – № 29. – Р. 1803–1811.
http://ascopubs.org/doi/full/10.1200/JCO.2010.33.3252
12. Shaknovich R., Melnick A. Epigenetics and B-cell lymphoma // Curr. Opin. Hematol.– 2011. – Vol. 18. №4. – P. 293-299.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260081/
13. Skibola C.F., Bracci P.M., Nieters A. Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium // Am J Epidemiol. – 2010. – Vol.171. № 3. – P. 267-276.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842204/pdf/kwp383.pdf
14. Swerdlow S.H. Campo E., Harris N.L. et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues // (Revised 4th edition). IARC: Lyon 2017.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842204/
15. Voropaeva E.N., Voevoda M.I., Maksimov V.N. et al. Prognostic impact of the TP53 rs1625895 polymorphism in DLBCL patients // British Journal of Haematology. – 2015. – Vol. 169. № 1. – P. 32-35.
https://www.ncbi.nlm.nih.gov/pubmed/?term=25430047
16. Weiner A.S., Beresina O.V., Voronina E.N., et al. Polymorphisms in folate-metabolizing genes and risk of non-hodgkin's lymphoma // Leukemia Research. – 2011. – Vol. 35. № 4. – P. 508-515.
https://www.ncbi.nlm.nih.gov/pubmed/21055808
17. Weiner A.S., Gordeeva L.A., Voronina E.N. et al. Polymorphisms in folate-metabolizing genes and risk of having an offspring with congenital anomalies in the West Siberian region of Russia: a case-control study // Prenat. Diagn. – 2012. – Vol. 32. № 11. – P. 1041-1048.
https://www.ncbi.nlm.nih.gov/pubmed/?term=22855024
http://sibmed.net/article.php?lang=rus&id_article=178
2. Воропаева Е.Н., Поспелова Т.И., Воевода М.И. Ассоциация полиморфизма Arg399Gln гена репарации ДНК XRCC1 с риском развития неходжкинских лимфом высокой степени злокачественности // Гематология и трансфузиология. –2013. – Т. 58. №1. – С. 10-14.
http://www.medlit.ru/journal/857
3. Воропаева Е.Н., Поспелова Т.И., Воевода М.И., Максимов В.Н. Результаты комплексного анализа статуса гена TP53 у больных диффузной В-крупноклеточной лимфомой // Гематология и трансфузиология. – 2016. – Т. 61. № 3. – С. 138-143.
http://www.medlit.ru/journalsview/haemathology/view/journal/2016/issue-3/
4. Поддубная И. В., Савченко В.Г. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний // Издательство ООО «Буки-Веди». – 2016. – Москва, 324 с.
http://www.hematology.ru/oncohematology/standarts/clinical_guidelines-draft.pdf
5. Cerhan J.R., Berndt S.I., Vijai J., Ghesquières H. et al. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma // Nat Genet. – Vol.46. № 11. – P. 1233-1238. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213349/
6. Christensen K.E., Deng L., Bahous R.H. MTHFD1 formyltetrahydrofolate synthetase deficiency, a model for the MTHFD1 R653Q variant, leads to congenital heart defects in mice // Birth Defects Res A Clin Mol Teratol. – 2015. – Vol. 103. № 12. – P. 1031-1038.
https://www.ncbi.nlm.nih.gov/pubmed/?term=26408344
7. Esteller M. Relevance of DNA methylation in the management of cancer // Lancet Oncol. – 2003. – № 4. – Р. 351–358.
https://www.ncbi.nlm.nih.gov/pubmed/?term=12788407
8. Galm O., Herman J.G., Baylin S.B. The fundamental role of epigenetics in hematopoietic malignancies // Blood Rev. – 2006. – Vol. 20. № 1. – Р. 1–13.
https://www.ncbi.nlm.nih.gov/pubmed/16426940
9. Koutros S., Zhang Y., Zhu Y. et al. Nutrients contributing to one-carbon metabolism and risk of non-Hodgkin lymphoma subtypes // American Journal of Epidemiology. – 2008. – Vol. 167. № 3. – P. 287 – 294.
https://academic.oup.com/aje/article/167/3/287/132137
10. Liu H., Jin G., Wang H. et al. Association of polymorphisms in one-carbon metabolizing genes and lung cancer risk: a case-control study in Chinese population // Lung Cancer. – 2008. – Vol. 61. №1. – P. 21-29.
https://www.ncbi.nlm.nih.gov/pubmed/?term=18221821
11. Nogai H., Dörken B., Lenz G. Pathogenesis of non-Hodgkin’s lymphoma // J. Clin. Oncol. – 2011. – № 29. – Р. 1803–1811.
http://ascopubs.org/doi/full/10.1200/JCO.2010.33.3252
12. Shaknovich R., Melnick A. Epigenetics and B-cell lymphoma // Curr. Opin. Hematol.– 2011. – Vol. 18. №4. – P. 293-299.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260081/
13. Skibola C.F., Bracci P.M., Nieters A. Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium // Am J Epidemiol. – 2010. – Vol.171. № 3. – P. 267-276.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842204/pdf/kwp383.pdf
14. Swerdlow S.H. Campo E., Harris N.L. et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues // (Revised 4th edition). IARC: Lyon 2017.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842204/
15. Voropaeva E.N., Voevoda M.I., Maksimov V.N. et al. Prognostic impact of the TP53 rs1625895 polymorphism in DLBCL patients // British Journal of Haematology. – 2015. – Vol. 169. № 1. – P. 32-35.
https://www.ncbi.nlm.nih.gov/pubmed/?term=25430047
16. Weiner A.S., Beresina O.V., Voronina E.N., et al. Polymorphisms in folate-metabolizing genes and risk of non-hodgkin's lymphoma // Leukemia Research. – 2011. – Vol. 35. № 4. – P. 508-515.
https://www.ncbi.nlm.nih.gov/pubmed/21055808
17. Weiner A.S., Gordeeva L.A., Voronina E.N. et al. Polymorphisms in folate-metabolizing genes and risk of having an offspring with congenital anomalies in the West Siberian region of Russia: a case-control study // Prenat. Diagn. – 2012. – Vol. 32. № 11. – P. 1041-1048.
https://www.ncbi.nlm.nih.gov/pubmed/?term=22855024
References
1. Berezina O.V., Pospelova T.I., Ovchinnikov V.S. et al. Glutathione-S-transferase m1 and t1 polymorphism (GSTM1 and GSTT1) in patients with non-Hodgkin's malignant lymphomas // Siberian Scientific Medical Journal. – 2013. – V. 33. №1. – P. 40-46.
http://sibmed.net/article.php?lang=rus&id_article=178
2. Voropaeva E.N., Pospelova T.I., Voevoda M.I. The association of Arg399Gln polymorphism of the XRCC1 DNA repair gene with a risk of developing non-Hodgkin's lymphomas of a high degree of malignancy // Hematology and Transfusiology. –2013. – V. 58. №1. – P. 10-14.
http://www.medlit.ru/journal/857
3. Voropaeva E.N., Pospelova T.I., Voevoda M.I., Maksimov V.N. The results of a comprehensive analysis of the status of the TP53 gene in patients with diffuse large B-cell lymphoma // Hematology and Transfusiology. – 2016. – V. 61. № 3. – P. 138-143.
http://www.medlit.ru/journalsview/haemathology/view/journal/2016/issue-3/
4. Poddubnaya I.V., Savchenko V.G. Russian clinical guidelines for the diagnosis and treatment of lymphoproliferative diseases // Publishing LLC «Buki-Vedi». – 2016. – Moscow, 324 p.
http://www.hematology.ru/oncohematology/standarts/clinical_guidelines-draft.pdf
5. Cerhan J.R., Berndt S.I., Vijai J., Ghesquières H. et al. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma // Nat Genet. – Vol.46. № 11. – P. 1233-1238.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213349/
6. Christensen K.E., Deng L., Bahous R.H. MTHFD1 formyltetrahydrofolate synthetase deficiency, a model for the MTHFD1 R653Q variant, leads to congenital heart defects in mice // Birth Defects Res A Clin Mol Teratol. – 2015. – Vol. 103. № 12. – P. 1031-1038.
https://www.ncbi.nlm.nih.gov/pubmed/?term=26408344
7. Esteller M. Relevance of DNA methylation in the management of cancer // Lancet Oncol. – 2003. – № 4. – Р. 351–358.
https://www.ncbi.nlm.nih.gov/pubmed/?term=12788407
8. Galm O., Herman J.G., Baylin S.B. The fundamental role of epigenetics in hematopoietic malignancies // Blood Rev. – 2006. – Vol. 20. № 1. – Р. 1–13.
https://www.ncbi.nlm.nih.gov/pubmed/16426940
9. Koutros S., Zhang Y., Zhu Y. et al. Nutrients contributing to one-carbon metabolism and risk of non-Hodgkin lymphoma subtypes // American Journal of Epidemiology. – 2008. – Vol. 167. № 3. – P. 287 – 294.
https://academic.oup.com/aje/article/167/3/287/132137
10. Liu H., Jin G., Wang H. et al. Association of polymorphisms in one-carbon metabolizing genes and lung cancer risk: a case-control study in Chinese population // Lung Cancer. – 2008. – Vol. 61. №1. – P. 21-29.
https://www.ncbi.nlm.nih.gov/pubmed/?term=18221821
11. Nogai H., Dörken B., Lenz G. Pathogenesis of non-Hodgkin’s lymphoma // J. Clin. Oncol. – 2011. – № 29. – Р. 1803–1811.
http://ascopubs.org/doi/full/10.1200/JCO.2010.33.3252
12. Shaknovich R., Melnick A. Epigenetics and B-cell lymphoma // Curr. Opin. Hematol.– 2011. – Vol. 18. №4. – P. 293-299.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260081/
13. Skibola C.F., Bracci P.M., Nieters A. Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium // Am J Epidemiol. – 2010. – Vol.171. № 3. – P. 267-276.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842204/pdf/kwp383.pdf
14. Swerdlow S.H. Campo E., Harris N.L. et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues // (Revised 4th edition). IARC: Lyon 2017.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842204/
15. Voropaeva E.N., Voevoda M.I., Maksimov V.N. et al. Prognostic impact of the TP53 rs1625895 polymorphism in DLBCL patients // British Journal of Haematology. – 2015. – Vol. 169. № 1. – P. 32-35.
https://www.ncbi.nlm.nih.gov/pubmed/?term=25430047
16. Weiner A.S., Beresina O.V., Voronina E.N., et al. Polymorphisms in folate-metabolizing genes and risk of non-hodgkin's lymphoma // Leukemia Research. – 2011. – Vol. 35. № 4. – P. 508-515.
https://www.ncbi.nlm.nih.gov/pubmed/21055808
17. Weiner A.S., Gordeeva L.A., Voronina E.N. et al. Polymorphisms in folate-metabolizing genes and risk of having an offspring with congenital anomalies in the West Siberian region of Russia: a case-control study // Prenat. Diagn. – 2012. – Vol. 32. № 11. – P. 1041-1048.
https://www.ncbi.nlm.nih.gov/pubmed/?term=22855024
Published
2018-10-28
How to Cite
БЕРЕЗИНА, Ольга Валерьевна; ПОСПЕЛОВА, Татьяна Ивановна.
FOLATE-METABOLIZING GENES IN DIFFUSE LARGE B-CELL LYMPHOMA.
Sibirskij Medicinskij Zurnal (Irkutsk) = Siberian Medical Journal (Irkutsk) 16+, [S.l.], v. 153, n. 2, p. 9-13, oct. 2018.
ISSN 1815-7572. Available at: <http://smj.ismu.baikal.ru/index.php/osn/article/view/272>. Date accessed: 28 jan. 2026.
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Section
Original research
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