Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms and Susceptibility to Childhood Acute Lymphoblastic Leukemia in an Iranian Population
,
Abstract
Background: The present study was aimed to examine the possible association between methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms and childhood acute lymphoblastic leukemia (ALL) in a sample of Iranian population.
Subjects and Methods: A total of 220 subjects including 100 children diagnosed with ALL and 120 healthy children participated in the case-control study. The single nucleotide polymorphisms (SNPs) of MTHFR were determined by ARMS-PCR or PCR-RFLP method.
Results:Our investigation revealed that rs13306561 both TC and TC + CC genotypes decreased the risk of ALL compared to TT genotype (OR=0.32, 95%CI=0.15-0.68, p=0.002 and OR=0.35, 95%CI=0.17-0.70, p=0.003, respectively). In addition, the rs13306561 C allele decreased the risk of ALL in comparison with T allele (OR=0.42, 95% CI=0.22-0.78, P=0.005). MTHFR rs1801131 (A1298C) polymorphism showed that the AC heterozygous genotype decreased the risk of ALL in comparison with AA homozygous genotype (OR=0.43, 95%CI=0.21-0.90, p=0.037). Neither the overall Chi-square comparison of cases and control subjects (x2=5.54, p=0.063) nor the logistic regression analysis showed significant association between C677T polymorphism and ALL (OR=1.25, 95% CI=0.69-2.23, p=0.552; CT vs. CC).
Conclusion: The current investigation findings showed that MTHFR rs1801131 and rs13306561 polymorphisms decreased the risk of ALL in the population which has been studied. Further studies with larger sample sizes and different ethnicities are required to validate our findings.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013; 63(1):11-30.
Kaatsch P. Epidemiology of childhood cancer. Cancer Treat Rev. 2010; 36(4):277-85.
Guo LM, Xi JS, Ma Y, et al. ARID5B gene rs10821936 polymorphism is associated with childhood acute lymphoblastic leukemia: a meta-analysis based on 39,116 subjects. Tumour Biol. 2014; 35(1):709-13.
Ma Y, Sui Y, Wang L, et al. Effect of GSTM1 null genotype on risk of childhood acute leukemia: a meta-analysis. Tumour Biol. 2014; 35(1):397-402.
Wiemels JL, Smith RN, Taylor GM, et al. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci U S A. 2001; 98(7):4004-9.
Franco RF, Simoes BP, Tone LG, et al. The methylenetetrahydrofolate reductase C677T gene polymorphism decreases the risk of childhood acute lymphocytic leukaemia. Br J Haematol. 2001; 115(3):616-8.
de Jonge R, Tissing WJ, Hooijberg JH, et al. Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia. Blood. 2009; 113(10):2284-9.
Sohn KJ, Jang H, Campan M, et al. The methylenetetrahydrofolate reductase C677T mutation induces cell-specific changes in genomic DNA methylation and uracil misincorporation: a possible molecular basis for the site-specific cancer risk modification. Int J Cancer. 2009; 124(9):1999-2005.
Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10(1):111-3.
van der Put NM, Gabreels F, Stevens EM, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998; 62(5):1044-51.
Kreile M, Rots D, Piekuse L, et al. Lack of Association between Polymorphisms in Genes MTHFR and MDR1 with Risk of Childhood Acute Lymphoblastic Leukemia. Asian Pac J Cancer Prev. 2014; 15(22):9707-11.
Silva RM, Fontes AC, Silva KA, et al. Polymorphisms involved in folate metabolism pathways and the risk of the development of childhood acute leukemia. Genet Test Mol Biomarkers. 2013; 17(2):147-52.
Xiao Y, Deng TR, Su CL, et al. Methylenetetrahydrofolate reductase polymorphisms and susceptibility to acute lymphoblastic leukemia in a chinese population: a meta-analysis. Oncol Res Treat. 2014; 37(10):576-82.
Dong S, Liu Y, Chen J. MTHFR gene polymorphism and risk of myeloid leukemia: a meta-analysis. Tumour Biol. 2014; 35(9):8913-9.
Hashemi M, Sheybani-Nasab M, Naderi M, et al. Association of functional polymorphism at the miR-502-binding site in the 3' untranslated region of the SETD8 gene with risk of childhood acute lymphoblastic leukemia, a preliminary report. Tumour Biol. 2014; 35(10):10375-9.
Hasani SS, Hashemi M, Eskandari-Nasab E, et al. A functional polymorphism in the miR-146a gene is associated with the risk of childhood acute lymphoblastic leukemia: a preliminary report. Tumour Biol. 2014; 35(1):219-25.
Hashemi M, Ebrahimi M, Amininia S, et al. Evaluation of rs3102735 and rs2073617 Osteoprotegerin Gene Polymorphisms and the Risk of Childhood Acute lymphoblastic Leukemia in Zahedan Southeast Iran. Int J Hematol Oncol Stem Cell Res. 2014; 8(4):39-44.
Bahari G, Hashemi M, Naderi M, et al. IKZF1 gene polymorphisms increased the risk of childhood acute lymphoblastic leukemia in an Iranian population. Tumour Biol. 2016. DOI: 10.1007/s13277-016-4853-0.
Hashemi M, Hanafi Bojd H, Eskandari Nasab E, et al. Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease. Hepat Mon. 2013; 13(5):e9527.
Sole X, Guino E, Valls J, et al. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006; 22(15):1928-9.
Balta G, Yuksek N, Ozyurek E, et al. Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. Am J Hematol. 2003; 73(3):154-60.
Li X, Liao Q, Zhang S, et al. Association of methylenetetrahytrofolate reductase (MTHFR) C677T and A1298C polymorphisms with the susceptibility of childhood acute lymphoblastic leukaemia (ALL) in Chinese population. Eur J Med Res. 2014; 19:5.
Azhar MR, Rahimi Z, Vaisi-Raygani A, et al. Lack of association between MTHFR C677T and A1298C polymorphisms and risk of childhood acute lymphoblastic leukemia in the Kurdish population from Western Iran. Genet Test Mol Biomarkers. 2012; 16(3):198-202.
Jiang N, Zhu X, Zhang H, et al. The relationship between methylenetetrahydrofolate reductase polymorphism and hematological malignancy. Clin Lab. 2014; 60(5):767-74.
Jiang Y, Hou J, Zhang Q, et al. The MTHFR C677T polymorphism and risk of acute lymphoblastic leukemia: an updated meta-analysis based on 37 case-control studies. Asian Pac J Cancer Prev. 2013; 14(11):6357-62.
Bellampalli R, Phani NM, Bhat KG, et al. Significance of 5,10-methylenetetrahydrofolate reductase gene variants in acute lymphoblastic leukemia in Indian population: an experimental, computational and meta-analysis. Leuk Lymphoma. 2015; 56(5):1450-9.
Sazawal S, Chaubey R, Kaur P, et al. MTHFR Gene Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Adults and Children: A Case Control Study in India. Indian J Hematol Blood Transfus. 2014; 30(4):219-25.
Schnakenberg E, Mehles A, Cario G, et al. Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to pediatric acute lymphoblastic leukemia in a German study population. BMC Med Genet. 2005; 6:23.
Zintzaras E, Doxani C, Rodopoulou P, et al. Variants of the MTHFR gene and susceptibility to acute lymphoblastic leukemia in children: a synthesis of genetic association studies. Cancer Epidemiol. 2012; 36(2):169-76.
Roy Moulik N, Parveen F, Kumar A, et al. MTHFR gene polymorphism in acute lymphoblastic leukemia among North Indian children: a case-control study and meta-analysis updated from 2011. J Hum Genet. 2014; 59(7):397-404.
Kim NK, Chong SY, Jang MJ, et al. Association of the methylenetetrahydrofolate reductase polymorphism in Korean patients with childhood acute lymphoblastic leukemia. Anticancer Res. 2006; 26(4B):2879-81.
Yan J, Yin M, Dreyer ZE, et al. A meta-analysis of MTHFR C677T and A1298C polymorphisms and risk of acute lymphoblastic leukemia in children. Pediatr Blood Cancer. 2012; 58(4):513-8.
Ojha RP, Gurney JG. Methylenetetrahydrofolate reductase C677T and overall survival in pediatric acute lymphoblastic leukemia: a systematic review. Leuk Lymphoma. 2014; 55(1):67-73.
Lin S, Liu Q, Zeng X. The association between methylenetetrahydrofolate reductase C677 > T polymorphisms and risk of pediatric acute lymphoblastic leukemia in Asia. J Cancer Res Ther. 2014; 10 Suppl: C210-4.
Atashrazm F, Zaker F, Aghaeipour M, et al. Polymorphisms of the methylene tetrahydrofolate reductase and susceptibility to acute lymphoblastic leukemia in children. Lab Medicine. 2011; 42(5):275-79.
| Files | ||
| Issue | Vol 10, No 3 (2016) | |
| Section | Articles | |
| Keywords | ||
| MTHFR Polymorphism Acute lymphocytic leukemia | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
