title: Polymorphisms of MTHFR and susceptibility to oesophageal adenocarcinoma in a Caucasian United Kingdom population.
abstract: OBJECTIVE
  To identify if methylene tetra-hydrofolatereductase (MTHFR) C677T polymorphisms are associated with oesophageal adenocarcinomas in a Caucasian population and to test whether folic acid and homocysteine levels are linked with cancer risk.
  
  
  METHODS
  A case control study comprising of 58 non cancer and 48 cancer patients, MTHFR C667T genotyping was made and serum folate, homocysteine and vitamin B12 levels were made. Tumour stage, differentiation and survival was recorded. A P value of less than 0.05 was taken to be significant. The χ(2) used to compare discrete variables and the Mantel-Cox was used to compare survival. A P value less than 0.05 was deemed to be significant.
  
  
  RESULTS
  MTHFR polymorphisms is associated with an increased risk of several cancers. A link between MTHFR C677T polymorphisms and oesophageal squamous cell carcinoma and gastric cardia adenocarcinoma has been demonstrated in at risk Chinese populations. In a Western European population the role of the MTHFR gene has not previously been investigated in the setting of oesophageal adenocarcinoma. No association between folic acid levels and cancer patients was found. The unstable MTHFR 667 TT genotype occurred in 11% cancers and 7% controls, but statistical significance was not reached, homocysteine levels and folic acid levels were not affected, cancer patients with TT genotype displayed a trend for a shorter survival 7 mo vs 20 mo. Serum vitamin B12 levels were higher in the cancer group. The MTHFR 667 TT genotype is much lower than previous population studies.
  
  
  CONCLUSIONS
  We conclude that serum folic acid and MTHFR polymorphisms are not associated with an increased risk of oesophageal adenocarcinoma, although cancers with unstable TT genotype may indicate a more aggressive disease course.
authors.affiliation: Richard Keld, Manyi Thian, Chia Hau, Jamil Sajid, Narveen Kumar, Yeng Ang, Department of Gastroenterology, Royal Albert Edward Infirmary, Wigan, Lancashire WN1 2NN, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Keld
authors.affiliation: Richard Keld, Manyi Thian, Chia Hau, Jamil Sajid, Narveen Kumar, Yeng Ang, Department of Gastroenterology, Royal Albert Edward Infirmary, Wigan, Lancashire WN1 2NN, United Kingdom.
authors.forename: Manyi
authors.initials: M
authors.lastname: Thian
authors.affiliation: Richard Keld, Manyi Thian, Chia Hau, Jamil Sajid, Narveen Kumar, Yeng Ang, Department of Gastroenterology, Royal Albert Edward Infirmary, Wigan, Lancashire WN1 2NN, United Kingdom.
authors.forename: Chia
authors.initials: C
authors.lastname: Hau
authors.affiliation: Richard Keld, Manyi Thian, Chia Hau, Jamil Sajid, Narveen Kumar, Yeng Ang, Department of Gastroenterology, Royal Albert Edward Infirmary, Wigan, Lancashire WN1 2NN, United Kingdom.
authors.forename: Jamil
authors.initials: J
authors.lastname: Sajid
authors.affiliation: Richard Keld, Manyi Thian, Chia Hau, Jamil Sajid, Narveen Kumar, Yeng Ang, Department of Gastroenterology, Royal Albert Edward Infirmary, Wigan, Lancashire WN1 2NN, United Kingdom.
authors.forename: Narveen
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Richard Keld, Manyi Thian, Chia Hau, Jamil Sajid, Narveen Kumar, Yeng Ang, Department of Gastroenterology, Royal Albert Edward Infirmary, Wigan, Lancashire WN1 2NN, United Kingdom.
authors.forename: Yeng
authors.initials: Y
authors.lastname: Ang
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D004938:Esophageal Neoplasms / Q000097:blood / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000097:blood; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D006113:United Kingdom; D044465:White People / Q000235:genetics*
chemical_list: D015415:Biomarkers; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Caucasian population; Helicobacter pylori; Oesophageal adenocarcinoma; Polymorphism; Polymorphisms of 5,10-methylenetetrahydrofolate reductase