title: Elevated homocysteine level and folate deficiency associated with increased overall risk of carcinogenesis: meta-analysis of 83 case-control studies involving 35,758 individuals.
abstract: BACKGROUND
  Results of the association of folate metabolism and carcinogenesis are conflicting. We performed a meta-analysis to examine the effect of the interaction of serum concentration of homocysteine (Hcy), folate, and vitamin B12 and 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism on risk of cancer overall.
  
  
  METHODS
  Two reviewers independently searched for all published studies of Hcy and cancer in PubMed, EMBASE-MEDLINE and Chinese databases. Pooled results were reported as odds ratios (ORs) and mean differences and presented with 95% confidence intervals (95% CIs) and 2-sided probability values.
  
  
  RESULTS
  We identified 83 eligible studies of 15,046 cases and 20,712 controls. High level of Hcy but low level of folate was associated with risk of cancer overall, with little effect by type of cancer or ethnicity. Vitamin B12 level was inversely associated with only urinary-system and gastrointestinal carcinomas and for Asian and Middle Eastern patients. As well, MTHFR C677T, A1298C and G1793A polymorphisms were related to elevated serum level of Hcy, and folate and vitamin B12 deficiency. However, only MTHFR C677T homogeneity/wild-type (TT/CC) polymorphism was positively associated with overall risk of cancer.
  
  
  CONCLUSIONS
  Elevated serum Hcy level and folate deficiency are associated with increased overall risk of cancer.
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Donghong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Fudan University Cancer Center, Shanghai, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000097:blood; D005494:Folic Acid Deficiency / Q000453:epidemiology* / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014571:Urologic Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000235:genetics
chemical_list: D006710:Homocysteine; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)