title: Association of methylenetetrahydrofolate dehydrogenase 1 polymorphisms with cancer: a meta-analysis.
abstract: BACKGROUND
  Studies investigating the association between single-nucleotide polymorphisms (SNPs) of the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and cancer risk report conflicting results. To derive a more precise estimation of the relationship between MTHFD1 polymorphisms and cancer risk, the present meta-analysis was carried out.
  
  
  RESULTS
  A comprehensive search was conducted to determine all the eligible studies about MTHFD1 polymorphisms and cancer risk. Combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association between the MTHFD1 polymorphisms and cancer risk. We investigated by meta-analysis the effects of 2 polymorphisms in MTHFD1: G1958A (17 studies, 12348 cases, 44132 controls) and G401A (20 studies, 8446 cases, 14020 controls). The overall results indicated no major influence of these 2 polymorphisms on cancer risk. For G1958A, a decreased cancer risk was found in acute lymphoblastic leukemia (ALL)/Asians (the dominant: OR = 0.74, 95% CI = 0.58-0.94, P = 0.01; allelic: OR = 0.80, 95% CI = 0.65-0.99, P = 0.04) and other cancers (recessive: OR = 0.80, 95% CI = 0.66-0.96, P = 0.02). For G401A, the data showed that MTHFD1 G401A polymorphism was associated with a decreased colon cancer risk under dominant model (OR = 0.89, 95% CI = 0.80-0.99, P = 0.04).
  
  
  CONCLUSIONS
  The results suggest that MTHFD1 G1958A polymorphism might be associated with a decreased risk of ALL and other cancers. Meanwhile, the MTHFD1 G401A might play a protective role in the development of colon cancer. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.
authors.affiliation: National Key Clinical Specialty of Urology, Second Affiliated Hospital of Tianjin Medical University, Tianjin Key Institute of Urology, Tianjin, China.
authors.forename: Hongtuan
authors.initials: H
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Ma
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D015778:Minor Histocompatibility Antigens; D009369:Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017594:Publication Bias
chemical_list: D015778:Minor Histocompatibility Antigens; C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)
references.citation: Leuk Res. 2011 Apr;35(4):508-15
references.pmid: 21055808
references.citation: J Biol Chem. 1997 Feb 7;272(6):3628-34
references.pmid: 9013615
references.citation: Mol Biol Rep. 2012 May;39(5):5553-60
references.pmid: 22183302
references.citation: Int J Cancer. 2004 Jul 1;110(4):617-20
references.pmid: 15122597
references.citation: Cancer Causes Control. 2007 Mar;18(2):143-52
references.pmid: 17206530
references.citation: Hematol Oncol. 2011 Sep;29(3):116-23
references.pmid: 20824655
references.citation: Nat Genet. 2007 May;39(5):645-9
references.pmid: 17401363
references.citation: Nat Rev Cancer. 2004 Nov;4(11):850-60
references.pmid: 15516958
references.citation: BMC Med Genet. 2007 Sep 19;8 Suppl 1:S6
references.pmid: 17903305
references.citation: J Biol Chem. 1953 Sep;204(1):403-16
references.pmid: 13084611
references.citation: Cancer Causes Control. 2011 Sep;22(9):1243-58
references.pmid: 21748308
references.citation: Lancet. 1991 Apr 13;337(8746):867-72
references.pmid: 1672966
references.citation: Br Med Bull. 1999;55(3):578-92
references.pmid: 10746348
references.citation: Nat Genet. 2006 Jun;38(6):652-8
references.pmid: 16682969
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Jul;19(7):1822-30
references.pmid: 20570913
references.citation: J Natl Cancer Inst. 1959 Apr;22(4):719-48
references.pmid: 13655060
references.citation: Control Clin Trials. 1986 Sep;7(3):177-88
references.pmid: 3802833
references.citation: Cancer. 2011 Feb 1;117(3):440-5
references.pmid: 20862743
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1140-7
references.pmid: 17548676
references.citation: Clin Biochem. 2011 Jun;44(8-9):596-600
references.pmid: 21349258
references.citation: Clin Gastroenterol Hepatol. 2005 Aug;3(8):743-51
references.pmid: 16234002
references.citation: Clin Genet. 2006 Jun;69(6):512-7
references.pmid: 16712703
references.citation: Mol Nutr Food Res. 2013 Apr;57(4):721-34
references.pmid: 22961839
references.citation: Am J Med Genet A. 2005 Feb 1;132A(4):365-8
references.pmid: 15633187
references.citation: Leuk Lymphoma. 2011 Sep;52(9):1770-6
references.pmid: 21657963
references.citation: JAMA. 1992 Jan 15;267(3):374-8
references.pmid: 1727960
references.citation: Mol Biol (Mosk). 2010 Sep-Oct;44(5):816-23
references.pmid: 21090237
references.citation: Gastroenterology. 2009 Jan;136(1):227-235.e3
references.pmid: 18992744
references.citation: Rev Assoc Med Bras (1992). 2011 Mar-Apr;57(2):194-9
references.pmid: 21537707
references.citation: PLoS One. 2013 Apr 04;8(4):e59570
references.pmid: 23593147
references.citation: Lung Cancer. 2007 Aug;57(2):143-51
references.pmid: 17420066
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Sep;18(9):2528-39
references.pmid: 19706844
references.citation: JAMA. 1998 Jan 28;279(4):281-6
references.pmid: 9450711
references.citation: Mol Biol Rep. 2010 Jan;37(1):241-7
references.pmid: 19649727
references.citation: J Biol Chem. 1988 Nov 5;263(31):15946-50
references.pmid: 3053686
references.citation: Nat Genet. 2008 Mar;40(3):316-21
references.pmid: 18264097
references.citation: Mol Biol Rep. 2012 Feb;39(2):887-93
references.pmid: 21630102
references.citation: Carcinogenesis. 2007 Aug;28(8):1672-9
references.pmid: 17449906
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3612-4
references.pmid: 19064578
references.citation: Nature. 2001 May 17;411(6835):366-74
references.pmid: 11357144
references.citation: Eur J Cancer. 2009 Sep;45(13):2391-401
references.pmid: 19501504
references.citation: Am J Hum Genet. 2002 Nov;71(5):1207-15
references.pmid: 12384833
references.citation: Eur J Cancer. 2012 Jul;48(10):1525-31
references.pmid: 22051736
references.citation: BMC Cancer. 2009 Apr 24;9:122
references.pmid: 19389261
references.citation: PLoS One. 2013;8(3):e58041
references.pmid: 23536781
references.citation: Curr Drug Metab. 2005 Feb;6(1):37-46
references.pmid: 15720206