Cyclin D1 (
CCND1), a key cell cycle regulatory protein that governs the cell cycle progression from G1 to S phase, can promote cell proliferation
or induce growth arrest and apoptosis. Since the identification of a well-characterized functional polymorphism, G870A in
exon 4 of
CCND1, several molecular epidemiological studies were conducted in recent years to evaluate the association between G870A and breast
cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis on
5,371 cases with breast cancer and 5,336 controls from 7 published case-control studies showed that the variant allele 870A
was associated with a significantly increased risk of breast cancer (AA vs. GG: OR = 1.18, 95% CI = 1.06–1.32; AG vs. GG:
OR = 1.12, 95% CI = 1.01–1.23; AA/AG vs. GG: OR = 1.14, 95% CI = 1.04–1.25) without any between-study heterogeneity. In the
stratified analysis by race, we found that the increased breast cancer risk associated with G870A polymorphism was more evident
in Caucasians (OR = 1.14, 95% CI = 1.01–1.28,
P = 0.88 for heterogeneity test), but not significant in Asians (OR = 1.10, 95% CI = 0.85–1.42,
P = 0.05 for heterogeneity test). The results suggest that
CCND1 G870A polymorphism may contribute to breast cancer development, especially in Caucasians. Additional well-designed large
studies were required for the validation of this association in different populations.
Keywords
CCND1
- Polymorphism - Breast Cancer - Meta-analysis
Cheng Lu and Jing Dong contributed equally to this work.