Background: Breast cancer is a major cause of morbidity and mortality in Jordan and worldwide. Abnormalityof 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 polymorphismsof MTHFR at two sites (C677T and A1298C) and their haplotypes and the risk of breast cancer among Jordanianfemales. Materials and
Methods: A case-control study involving 150 breast cancer cases and 150 controlswas conducted. Controls were age-matched to cases. Polymerase chain reaction/restriction fragment lengthpolymorphism (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 frequencyof 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 polymorphismhaplotypes 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 ofMTHFR C677T may modulate the risk of breast cancer especially in the 41-60 year age group. Additionally, TAhaplotype amends the risk of breast cancer. Future studies with a larger sample size are needed to validate therole of MTHFR genetic polymorphisms in breast cancer.