title: Polymorphisms in methylenetetrahydrofolate reductase gene (MTHFR) and the age of onset of sporadic colorectal adenocarcinoma.
abstract: OBJECTIVE
  Evidence is accumulating for a role of folate in the aetiology of colorectal cancer (CRC). The methylenetetrahydrofolate reductase (MTHFR) gene, involved in folate metabolism, is polymorphic in humans. Since it is unknown whether the MTHFR C677T and A1298C polymorphisms alter the risk for CRC, this was the aim of our study.
  
  
  METHODS
  Genomic DNA from 102 sporadic colorectal adenocarcinoma (SCA) patients and 300 controls was analyzed by polymerase chain reaction followed by restriction digestion for the polymorphisms analyses.
  
  
  RESULTS
  The frequencies of MTHFR C677T and A1298C genotypes were similar in patients and controls. Similar overall risks for disease were seen in individuals with the distinct MTHFR genotypes. However, an excess of the MTHFR 677TT and 677CT genotypes was seen in patients under 50 years, compared with patients at an older age (19.2 vs 13.1% and 61.6 vs 39.5%, respectively; P = 0.04). The differences were more prominent when the frequency of the 677TT plus 677CT genotype was seen in both group of patients (80.8 vs 52.6%, respectively; P = 0.01), and in younger patients compared to controls (80.8 vs 52.3%, P < 0.01). Individuals with the combined genotype had 3.82-fold (95% confidence interval, 1.41-10.42) increased risk of developing SCA under 50 years, compared with those harboring the wild-type genotype.
  
  
  CONCLUSIONS
  These results suggest a role for the MTHFR 677TT plus 677CT genotype in increasing SCA diagnosed at a low age in southeastern Brazil, but additional studies with larger sample sizes should be carried out to clarify this issue.
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, CP: 6111, 13083-970, Brazil. carmenl@fcm.unicamp.br
authors.forename: Carmen S P
authors.initials: CS
authors.lastname: Lima
authors.forename: Helvia
authors.initials: H
authors.lastname: Nascimento
authors.forename: Luciana C
authors.initials: LC
authors.lastname: Bonadia
authors.forename: Maria T
authors.initials: MT
authors.lastname: Teori
authors.forename: Claudio S R
authors.initials: CS
authors.lastname: Coy
authors.forename: Juvenal R N
authors.initials: JR
authors.lastname: Góes
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Costa
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Bertuzzo
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D000367:Age Factors; D017668:Age of Onset; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D042965:Methylenetetrahydrofolate Reductase (NADPH2)