AA genotype of cyclin D1 G870A polymorphism increases breast cancer risk: Findings of a case‐control study and meta‐analysis

Background Cyclin D1 (CCND1) polymorphisms, a regulator of the cell cycle progress from G1 to the S phase, may lead to uncontrolled cell proliferation and lack of apoptosis. G870A, a common single‐nucleotide polymorphism in CCND1 influences breast cancer risk. However, the association between G870A polymorphism and breast cancer risk is ambiguous so far. Materials and Methods In this case‐control study, we analyzed the role of G870A polymorphism with breast cancer risk in Indian women. A meta‐analysis of 18 studies was also performed to elucidate this association by increasing statistical power. Results In our case‐control study, significant risk association of the CCND1 G870A AA genotype with breast cancer in total cohort (odds ratio [OR], 2.98; 95% confidence interval [CI], 1.64‐5.42; P value, 4.96e‐04) and premenopausal women (OR, 3.31; 95% CI, 1.54‐7.08; P value, .003) was found. The results of the meta‐analysis showed that AA genotype of the CCND1 G870A polymorphism significantly increases breast cancer risk in total pooled data (AA vs GG+GA: OR = 1.20; 95% CI = 1.03 to 1.39; P value, 0.016*) and Caucasian (AA vs GG+GA: OR = 1.22; 95% CI = 0.99 to 1.51; P value, .056*) but not in Asian population. Further, a significant protective association with breast cancer was also found in the GA vs AA comparison model in pooled data (OR = 0.73; 95% CI = 0.58 to 0.92; P value, .007*) as well as in Caucasian subgroup (OR = 0.62; 95% CI = 0.49 to 0.94; P value, .022*). Conclusion CCND1 G870A AA genotype was found associated with breast cancer risk. Future association studies considering the environmental impact on gene expression are required to validate/explore this association. Cyclin D1 polymorphisms may lead to uncontrolled cell proliferation. G870A single‐nucleotide polymorphism influences breast cancer risk. Our study shows that AA genotype is significantly associated with breast cancer risk.