Folate cycle and xenobiotic biotransformation system genes as markers of development risk of non-hodgkin malignant lymphomas in the residents of Novosibirsk
Author Affiliations1Novosibirsk State Medical University of Miszdrav of Russia 630091, Novosibirsk, Krasny av., 52
2Institute for Chemical Biology and Fundamental Medicine of SB RAS 630090, Novosibirsk, Akademic Lavrentiev av., 8
3Novosibirsk State Medical University of Miszdrav of Russia 630091, Novosibirsk, Krasny av., 52
4Institute for Chemical Biology and Fundamental Medicine of SB RAS 630090, Novosibirsk, Akademic Lavrentiev av., 8
Abstract
Changes in folate cycle and xenobiotic biotransformation system genes may cause the different susceptibility to non-Hodgkin's lymphomas (NHL). In the present study the association between seven single nucleotide substitutions in the folate cycle genes and deletions in genes of glutathione-S-transferase M1 and T1 (GSTM1 and GSTT1) with genetic risk of NHL was investigated. Association of 1958A-mutant allele with decreased aggressive lymphoma risk was revealed for polymorphic locus G1258A MTHFD1 (OR = 0.578, CI [0.415-0.805], p < 0.001). The combination of mutant 1420T alleles in homozygous T/T-genotype of SHMT1 gene may cause an increased aggressive lymphoma risk in 2.2 times (p < 0.02). The carriers of the mutant GSTM1 genotype have increased follicular lymphoma risk (OR = 1.96, CI [1.072-3.581], p < 0.02). Thus, these polymorphic variants may play a role in the pathogenesis of NHL and be used in non-Hodgkin's lymphomas diagnosis.
Key words
References1. Baranov V.S. Genetic passport - the basis of individual and predictive medicine. Spb, 2009.528 p. (in Russian)
2. Volkova M.A. Clinical oncogematology. Moscow: Meditsina, 2007. 1120 p. (in Russian)
3. Voropaeva E.N., Skvortsova N.V., Voevoda M.I., Tarnovsky R.V. Clinical significance of CCR5 gene deletion at patients with non-hodgkin lymphomas. Byulleten' Sibirskogo otdeleniya Rossiyskoy akademii meditsinskikh nauk. 2011. 31. (2). 20-25. (in Russian)
4. Imyanitov E.N., Hanson K.P. Molecular genetics in clinical oncology // Sibirskiy onkologicheskiy zhurnal. 2004. 2-3 (10-11). 40-47. (in Russian)
5. Pospelova T.I., Voropaeva E.N., Voevoda M.I., Berezina O.V. P53 gene polymorphism as a potential marker of susceptibility to non-hodgkin malignant lymphomas // Gematologiya I transfuziologiya. 2010. 55. (1). 11-17. (in Russian)
6. Agodi A., Barchitta M., Cipresso R. et al. Distribution of p53, GST, and MTHFR polymorphisms and risk of cervical intraepithelial lesions in Sicily // Int. J. Gynecol. Cancer. 2010. 20. (1). 141-146.
7. Avti P.K., Vaiphei K., Pathak C.M., Khanduja K.L. Involvement of various molecular events in cellular injury induced by smokeless tobacco // Chem. Res. Toxicol. 2010. 2. (7). 1163-1174.
8. Berglund M., Enblad G., Turesson I. et al. Folate-metabolizing genes in lymphoma patients from Sweden // Scand. J. Immunol. 2009. 70 (4). 408-410.
9. Christensen K.E., Rohlicek C.V., Andelfinger G.U. et al. The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects // Hum. Mutat. 2009. 30. (2). 212-220.
10. Hohaus S., Mansueto G., Massini G. et al. Glutathione-S-transferase genotypes influence prognosis in follicular non-Hodgkin's Lymphoma // Leuk. Lymphoma. 2007. 48. (3). 564-569.
11. Koutros S., Zhang Y., Zhu Y. et al. Nutrients contributing to one-carbon metabolism and risk of non-Hodgkin lymphoma subtypes // Am. J. Epidemiol. 2008. 167 (3). 287-294.
12. Lim U., Schenk M., Kelemen L.E. et al. Dietary determinants of one-carbon metabolism and the risk of non-Hodgkin's lymphoma: NCI-SEER case-control study, 1998-2000 // Am. J. Epidemiol. 2005. 162 (10). 953-964.
13. Linet M.S., Pottern L.M. Familial aggregation of hematopoietic malignancies and risk of non-Hodgkin's lymphoma // Cancer Res. 1992. 52 (19). 5468-5473.
14. Niclot S., Pruvot Q., Besson C. et al. Implication of the folate-methionine metabolism pathways in susceptibility to follicular lymphomas // Blood. 2006. 108 (1). 278-85.
15. Paz M.F., Avila S., Fraga M.F. et al. Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumors // Cancer Res. 2002. 62. (15). 4519-4524.
16. Polesel J., Dal Maso L., La Vecchia C. et al. Dietary folate, alcohol consumption, and risk of non-Hodgkin lymphoma // Nutr. Cancer. 2007. 57. (2). 146-150.
17. Sabbatini E., Bacci F., Sagramoso C., Pileri S.A. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview // Pathologica. 2010. 102. (3). 83-87.
18. Segel G.B., Lichtman M.A. Familial (inherited) leukemia, lymphoma, and myeloma: an overview // Blood Cells Mol. Dis. 2004. 32. (1). 246-261.
19. Skibola C.F., Forrest M.S., Coppede F. et al. Polymorphisms and haplotypes in folate-metabolizing genes and risk of non-Hodgkin lymphoma // Blood. 2004. 104. 2155-2162.
20. Skibola C.F., Smith M.T., Hubbard A. et al. Polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and risk of adult acute lymphocytic leukemia // Blood. 2002. 99. 3786-3791.
21. Wang L., Ke Q., Chen W. et al. Polymorphisms of MTHFD, plasma homocysteine levels, and risk of gastric cancer in a high-risk Chinese population // Clin. Cancer Res. 2007. 13. (8). 2526-2532.
22. Zhang Z., Deng X., Ren X., Zhang B. et al. Expression of mutant p53 and of the multidrug resistant proteins P-glycoprotein and glutathione S-transferase-pi correlated in colorectal adenocarcinoma // Scand. J. Gastroenterol. 2010. 45. (7-8). 925-934.
About Authors (Correspondence):
Berezina O.V. - candidate of medical sciences, assistant of the chair for therapy, hematology and blood transfusiology, e-mail: ovberezina@mail.ru
Shadrina A.S. - senior assistant of the pharmacogenomic laboratory, e-mail: hamlet85@yandex.ru
Pospelova T.I. - doctor of medical sciences, professor, the head of the chair for therapy, hematology and transfusiology, e-mail: post_gem@mail.ru.
Filipenko M.L. - candidate of biological sciences, head of the pharmacogenomic laboratory, e-mail: max@niboch.nsc.ru
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