Table 5, demonstrates that the most frequent haplotype of the two loci of MTHFR (rs1801133-rs1801131) was TC which was strongly associated with the aggressive clinical features of each of big tumor size, advanced stage, involvement of cancer in lymph nodes, overexpression of HER2neu and dual negativity of both ER and PR hormones giving highly significant P values (0.001). This evidence concerns the gene ESR1 and cancer.