ABSTRACT
Breast cancer (BC) is a multistep disease that is thought to result from an interaction between genetic background and environmental factors. In Iran, one of the strongest risk factors for developing BC is a positive family history of the disease. Recently, various polymorphisms of E-cadherin (CDH1) and TERT have been found to be associated with increased BC risk worldwide. This study aimed to analyze the association of CDH1 and TERT single-nucleotide polymorphisms with susceptibility to familial BC (FBC) risk in the Iranian patients. One hundred five patients with FBC and 110 non-FBC (NFBC) were genotyped to elucidate the potential association between CDH1 rs5030625 polymorphism and TERT rs2736098 polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Then, results were evaluated by electrophoresis and Epi Info(™) 2012 software. A significant association was found between CDH1 rs5030625 GAGA genotype and FBC risk. Compared with the control group, the FBC patients had a lower frequency of GG genotype (69% vs. 85%) and a higher frequency of GAGA (5% vs. 2%, P < 0.02). Furthermore, the patients with FBC had a lower frequency of TERT rs2736098 GG genotype (38% vs. 49%, P = 0.001) and a higher frequency of rs2736098 AA genotype (12% vs. 5%, P = 0.001) compared with the NFBC. In contrast, the TERT rs2736098 GG genotype potentially increased the recurring risk of FBC (odds ratio = 3.17, P < 0.01). Allele genotypic frequencies in the FBC patients differed from those of the controls. Interestingly, tumors in FBC patients with rs2736098 GG genotype and rs5030625 GAGA exhibited higher mitotic activity, higher grade, lower estrogen receptor, and progesterone receptor than the other genotypes. In conclusion, CDH1 rs5030625 GAGA genotype and TERT rs2736098 GG genotype in combination with clinical parameters may be prognostic factors rather than susceptibility factors during the progression of FBC.