No association between a progesterone receptor gene promoter polymorphism (+331G>A) and breast cancer risk in Caucasian women: evidence from a literature-based meta-analysis

Sex steroid hormones and their receptors such as estrogen receptor (ER) and progesterone receptor (PgR) have been widely studied for their roles in the etiology of breast cancer. To date, many studies have evaluated the association between a functional polymorphism in the PgR gene promoter (+331G > A, rs10895068) and breast cancer risk; however, the result is still ambiguous and inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was performed in this study. By searching relevant literature, a total of 10 studies containing 13,702 cases and 14,726 controls (28,428 subjects in total) were identified and meta-analyzed. All the study subjects were Caucasian women. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the codominant model, dominant model, and recessive model. Overall, no significant association between +331G > A polymorphism and breast cancer susceptibility was observed for AA versus GG (OR = 0.940, 95% CI: 0.566-1.562), GA versus GG (OR = 1.061, 95% CI: 0.888-1.267), AA + GA versus GG (OR = 1.074, 95% CI: 0.956-1.207), and AA versus GA + GG (OR = 0.951, 95% CI: 0.586-1.544). Sensitivity analysis was performed by limiting the meta-analysis to those studies fulfilling Hardy-Weinberg equilibrium, and the results were not materially altered in any genetic model. In conclusion, the present meta-analysis strongly suggests that +331G > A in the PgR gene is not associated with breast cancer risk.