Association of CCND1 Gene c.870G > A Polymorphism with Breast Cancer Risk: A Case-ControlStudy and a Meta-Analysis

Abstract

Cyclin D1 (CCND1) plays an essential role in regulating the progress of the cell cycle from G1 to S phase. There is a common c.870G > A polymorphism in the CCND1 gene. The aim of this study was to investigate the association of CCND1 gene c.870G > A polymorphism with breast cancer risk in a case-control study, which followed by a meta-analysis and an in silico analysis. Three hundred and thirty-five subjects composed of 174 women with breast cancer and 161 healthy controls were included in the case-control study. CCND1 gene c.870G > A genotyping was performed by PCR-RFLP. Meta-analysis was done for 14 studies composed of 7281 cases and 6820 controls. Some bioinformatics tools were applied to investigate the effects of c.870G > A on the mRNA splicing and structure. Our data obtained from case-control study revealed that GA genotype (OR: 1.89, 95%CI: 1.12-3.17, p = 0.017), AA genotype (OR: 1.95, 95%CI: 1.08-3.53, p = 0.027), and A allele (OR: 1.44, 95%CI: 1.06-1.95, p = 0.019) were significantly associated with breast cancer risk. The results of meta-analysis showed a significant association between CCND1 c.870G > A polymorphism and breast cancer risk, especially in Caucasian population. In silico analysis revealed that c.870G > A transition affect CCND1 mRNA splicing and secondary structure.