Selection and characteristics of eligible studies
According to the inclusion and exclusion criteria, a total of 14 studies [14, 16-19, 24-32] were deemed eligible for this meta-analysis (Figure 1 detailed the study selection process). Among them, 8 studies investigated only the Arg264Cys polymorphism [14, 16-18, 24-26, 28], 5 studies explored only the (TTTA)n repeat polymorphism[19, 29-32], and 1 study focused on both polymorphisms. The main characteristics of these studies are listed in Supplementary Table 1 (see Additional file 1) and Supplementary Table 2 (see Additional file 2). The NOS scores were equal or greater than 5 for all included publications.
Association between the CYP19A1 Arg264Cys polymorphism and PCa risk
Nine studies (7 case-control studies and 2 nested case-control studies), which recruited a total of 11,824 patients and 11,368 control subjects, addressed the relationship between the Arg264Cys polymorphism and PCa (see Supplementary Table 1)[14, 16-18, 24-28]. These studies enrolled Caucasians (4 studies), Asians (2 studies), Indians (1 study), African-Americans (1 study), and subjects of mixed ethnicities (1 study). One study employed intervention measures that might confer PCa risk; therefore, only data in the placebo arm were considered . In 2 studies, genotype distributions in the control groups deviated from HWE [14, 18]. Controls were hospital-based (HB) in 3 studies, population-based (PB) in 5 studies, and both HB and PB in 1 study. One study merely recruited cases with a family history of PCa in a first-degree relative , 1 study described the ratio of familial cases in all participants , while the remaining 7 studies did not provide information about family history.
The overall pooled results and subgroup analyses are listed in Table 1. Neither the T allele nor the TT genotype was associated with PCa in the overall population, Caucasians, or Asians. Subgroup analyses could not be performed for African-Americans, Indians, or mixed ethnicities since each of these ethnicities was included only in one study. Thus, although both the CT and CT+TT genotypes were significantly related to PCa risk in Indians in the work of Onsory, these results should be treated cautiously. Subgroup analysis stratified by the source of controls was also conducted (Figure 2). When PB controls were considered, no evident association was found between the Arg264Cys polymorphism and PCa in any genetic model. Nevertheless, an association between the Arg264Cys polymorphism and PCa was observed under the dominant model (CT+TT vs. CC: OR=1.35, 95%CI=1.02-1.78, P=0.04) (Figure 2) and heterozygous model (CT vs. TT: OR=1.40, 95%CI=1.04-1.88, P=0.03) in the HB subgroup. Subgroup analysis could not be accomplished for the PB+HB subgroup since only one study included PB+HB controls.
Association between the CYP19A1 (TTTA)n repeat polymorphism and PCa risk
Six studies (5 case-control studies and 1 nested case-control study) which recruited a total of 1488 cases and 1621 controls were analyzed (see Supplementary Table 2)[19, 27, 29-32]. Three of them were conducted in Asians, 1 each in Caucasians,Indians and subjects of mixed ethnicities. The repeat numbers ranged from 7 to 14, but the 9-repeat allele was not detected in 4 studies [29-32] , and the 14-repeat allele was identified only in 1 study . Thus, the 7-, 8-, and 10-13-repeat alleles were considered in this meta-analysis. Soni and coworkers  did not find 10, 11, and 13 repeats either in patients or in controls, so that their study could not be included in the analysis of these three alleles. For the same reason, the study of Tang  was not used in the analysis of the 13-repeat allele.
The pooled results are listed in Table 2. Only the 8-repeat allele was significantly associated with the risk of PCa in the overall population (OR=1.34, 95%CI=1.14-1.58, P=0.001) (Figure 3), while all the other alleles appeared not related to the overall PCa risk. Among the 6 studies addressing the 8-repeat allele, 1 was performed in Caucasians, 3 in Asians, 1 in Indians, and 1 in subjects of mixed ethnicities. Therefore, subgroup analysis only applied to Asians and yielded a non-significant result (OR=1.27, 95%CI=0.88-1.85, P=0.17). Although the study conducted in subjects of mixed races concluded that the 8-repeat allele increased the risk of PCa (OR=1.41, 95%CI=1.09-1.82, P=0.01), the results based on one study should be treated cautiously due to low statistical power . In the subgroup analysis based on the source of controls, the 8-repeat allele was a risk factor of PCa in the PB subgroup (OR=1.41, 95%CI=1.13-1.74, P=0.002) (Figure 3).
Heterogeneity and Sensitivity Analysis
Although there was considerable heterogeneity among the studies on the two polymorphisms (Table 1 and Table 2), sensitivity analysis showed that the synthetic results were not materially altered by omitting any single study, indicating the stability of the results (Figure 4 and Figure 5).
Begg’s funnel plots did not reveal any evidence of obvious asymmetry in studies on the Arg264Cys polymorphism (Figure 6), and Egger’s test with P>0.05 further verified the absence of publication bias (Table 1). For the (TTTA)n repeat polymorphism, Begg’s funnel plots and Egger’s test indicated the absence of publication bias except for the 7-, 8- and 13-repeat alleles (P<0.05; Table 2).