Determination of the predictive and prognostic values of polymorphism of some cell cycle genes in breast cancer

Abstract

Aim: To investigate the influence of the polymorphic variants of CCND1 (G870A) and p73 (G4C14-to-A4T14) on the susceptibility to breast cancer development, also, to figure out their diagnostic and prognostic roles. Subjects and Methods: Blood samples were obtained from breast cancer patients and controls. Genotyping of CCND1 and p73 genes were carried out by PCR-RFLP and PCR-CTPP; respectively. Results: In comparison with the control group, CCND1 (G870A) GA and AA genotypes frequencies were significantly higher in breast cancer patients (p=0.035 and p=0.002; respectively), whereas CCND1 (G870A) GG genotype frequency was significantly lower (p< 0.001). The CCND1 GA and AA genotypes significantly increased the risk for developing breast cancer compared with the GG genotype. The CCND1 (GA+AA) genotypes were significantly correlated with disease-free survival (DFS) of breast cancer patients. In comparison with the control group, p73 (G4C14/A4T14) GC/AT and AT/AT genotypes frequencies were significantly higher in breast cancer patients (p=0.013 and p=0.04; respectively), whereas p73 (G4C14/A4T14) GC/GC genotype frequency was significantly lower (p= 0.004). Compared with the GC/GC genotype, the p73 GC/AT and AT/AT genotypes significantly increased the risk for developing breast cancer. Beside being significantly correlated with DFS, p73 [(GC/AT)+ (AT/AT)] genotypes were indirectly correlated with tumor size, tumor pathological grade, patient's clinical stage, number of axillary lymph node involvement and Her2/neu expression. Conclusion: The GA and AA genotypes of CCND1 (G870A) polymorphism and the GC/AT and AT/AT genotypes of p73 (G4C14-to-A4T14) polymorphism can be used as diagnostic markers in breast cancer patients. The presence of the CCND1 (G870A) GA and AA genotypes and the GC/AT and AT/AT genotypes of p73 (G4C14-to-A4T14) polymorphism can increase the susceptibility to breast cancer incidence. Both of CCND1 (G870A) and p73 (G4C14-to-A4T14) polymorphisms can be used for prognosis of breast cancer patients.

Association between TP73 G4C14-A4T14 polymorphism and different cancer types: an updated meta-analysis of 55 case–control studies

“…Fifty-five case–control studies 2 , 24 – 74 including 15,648 cancer cases and 19,159 controls met the eligibility criteria and were finally included in this meta-analysis ( Figure 1 ). A total of 194 studies were excluded after screening the title, abstract and full-text, because of irrelevant information, incomplete genetic data, or duplicate contents.…”

“…Decreased expression of p73 mRNA was identified in both inflammatory and non-inflammatory BC cells compared with normal breast epithelial cells, indicating that this variant might increase the risk of BC by reducing the expression of p73. A recent study postulated that the TP73 GC/AT and AT/AT genotypes could increase the susceptibility to BC, while another study found that the GC/GC genotype was associated with an increased risk of triple-negative BC, 2 , 37 , 66 and yet another study found no significant association between this polymorphism and BC. 62 Similar findings were observed in EC studies with contradictory conclusions.…”

“…Given its ability to modify the tumor suppression activity of TP73 , the association between G4C14-A4T14 and carcinogenesis has recently been investigated in genome-wide association studies in multiple cancer types, including lung, colorectal, breast, cervical, gastric, esophageal, endometrial, oral, and ovarian cancer, in addition to head and neck squamous cell carcinoma, lymphoma, and cutaneous melanoma. 2 , 24 – 74 However, the findings of these studies were inconsistent. Although previous meta-analyses have summarized the evidence regarding the roles of the G4C14-A4T14 polymorphism in different cancers, the numbers of studies included in those meta-analyses were limited, 75 – 78 While a larger sample size provides firmer evidence in population-based genetic association studies.…”