title: Relationship between Genetic Polymorphisms in MTHFR (C677T, A1298C and their Haplotypes) and the Incidence Of Breast Cancer among Jordanian Females--Case-Control Study.
abstract: BACKGROUND
  Breast cancer is a major cause of morbidity and mortality in Jordan and worldwide. Abnormality of DNA methylation is a possible mechanism for the development of cancer. Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation. Our aim was to study the association between genetic polymorphisms of MTHFR at two sites (C677T and A1298C) and their haplotypes and the risk of breast cancer among Jordanian females.
  
  
  METHODS
  A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. Polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique and sequencing were conducted to determine the genotypes.
  
  
  RESULTS
  There was a significant difference in genotype frequency of C677T in the 41-60 year age category [cases: CC (37.4%), CT (49.5%) and TT (13.2%); controls: CC (56.3%), CT (35.6%) and TT (8%), p=0.04; ORTT vs. CC: 2.5, 95% CI: (0.9-6.9); ORat least on T: 2.1, 95%CI: (1.2-3.9)]. There was no significant difference in genotype frequency of A1298C between cases and controls [cases: AA (46.6%), AC (41.8%) and CC (11.6%); controls: AA (43%), AC (47.4%) and CC (9.6%); p=0.6]. There was a significant difference of MTHFR genetic polymorphism haplotypes among breast cancer cases and controls [cases/control: CA: 38.3/45.4%; CC: 28.9/25.2%; TA: 29.2/21; TC: 3.6/8.3; p value=0.01; ORTA vs. CA=1.6; 95% CI (1.1-2.5); p=0.02].
  
  
  CONCLUSIONS
  Genetic polymorphism of MTHFR C677T may modulate the risk of breast cancer especially in the 41-60 year age group. Additionally, TA haplotype amends the risk of breast cancer. Future studies with a larger sample size are needed to validate the role of MTHFR genetic polymorphisms in breast cancer.
authors.affiliation: Biopharmaceutics and Clinical Pharmacy, Department of Pharmacy, The University of Jordan , Amman, Jordan E-mail : Nemah91@hotmail.com.
authors.forename: Nemah
authors.initials: N
authors.lastname: Awwad
authors.forename: Al-Motassem
authors.initials: AM
authors.lastname: Yousef
authors.forename: Ali
authors.initials: A
authors.lastname: Abuhaliema
authors.forename: Ihab
authors.initials: I
authors.lastname: Abdalla
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yousef
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007597:Jordan; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)