title: Intraindividual somatic variations in MTHFR gene polymorphisms in relation to colon cancer.
abstract: OBJECTIVE
  MTHFR mediates the one carbon metabolism pathway. Two common genetic variants, C677T and A1298C, of MTHFR are associated with number of human diseases, including cancer, as well as being involved in the modulation of therapy outcome to antifolate drugs. To understand the distribution pattern of SNPs among different tissues of an individual, we examined MTHFR polymorphisms in normal and colon cancer tissues and compared the genotype frequencies in peripheral blood samples.
  
  
  METHODS
  DNA was isolated from tumor tissue and matched normal tissues from 155 colon cancer patients. These samples as well as DNA from blood samples of the control group (n = 294) were analyzed for MTHFR polymorphisms by PCR-RFLP and confirmed by a direct DNA sequencing method.
  
  
  RESULTS
  Our data suggest that the allele and genotype frequencies of C677T and A1298C were significantly different between tumor tissues and both types of normal tissues. We have established that MTHFR variants that exist in tumor and matched normal tissues of colon cancer patients differ suggesting somatic variation in MTHFR polymorphisms among different tissues of an individual. The MTHFR A1298C polymorphism was associated with risk of colon cancer.
  
  
  CONCLUSIONS
  Different MTHFR variants may exist in different tissues to maintain physiological functions and may have implications for disease susceptibility and pharmacogenomics based therapies. Original submitted 21 January 2013; Revision submitted 3 January 2014.
authors.affiliation: Division of Biotechnology, School of Life Sciences, Planetarium Complex, Manipal University, Manipal-576104, India.
authors.forename: Padmalatha S
authors.initials: PS
authors.lastname: Rai
authors.forename: Ganesh C
authors.initials: GC
authors.lastname: Pai
authors.forename: Jose F
authors.initials: JF
authors.lastname: Alvares
authors.forename: Ravishankara
authors.initials: R
authors.lastname: Bellampalli
authors.forename: Puthiya M
authors.initials: PM
authors.lastname: Gopinath
authors.forename: Kapaettu
authors.initials: K
authors.lastname: Satyamoorthy
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)