Journal of Experimental & Clinical Cancer Research 2009, 28:135 http://www.jeccr.com/content/28/1/135 Table 2: Crude and Adjusted Prostate Cancer Risk Estimates Cs/Coa Crude ORb 95% CIc Adjusted ORd 10/37 9/37 7/36 7/37 7/37 12/36 11/37 9/37 6/36 2OHE1 1st tertile 2nd tertile 3rd tertile trend P for trend 16OHE1 1st tertile 2nd tertile 3rd tertile trend P for trend 2OHE1/16OHE1 1st tertile 2nd tertile 3rd tertile trend P for trend ≤ 0.21 0.21 - 2.26 > 2.26 ≤ 61.84 61.84 - 158.74 >158.74 ≤ 0,31 0.31-1.64 > 1.64 a matched on age, race and recruitment period b odds ratio; c95% confidence interval; dadjusted for age across tertiles (OR 0.56, 95% CI 0.19-1.68, in the highest tertile). When we tested the independent variables of interest for significance in trends of associations, none of the models produced significant results. Analyzing data by subsets including only one of the two outcome variables did not affect the study results at any level. From the case-case and control-control comparison, no significant differences emerged between the partici- pants who had been included in the present analyses and those who had been excluded because of missing data items. Results of the systematic review Our search of the literature yielded a total of 289 unique citations. Based on the titles and abstracts screening of the retrieved citations, only our previously conducted case- control study [13] and the study from Yang and colleagues [24] met the eligibility criteria. Unfortunately, we could not include the latter manuscript in our meta-analysis. In the study from Yang et al the whole control group, which itself represents the vast majority of the overall sample (118/139), is part of the Western New York Health Cohort and directly stems from the recall process carried out between January 2003 and September 2004 as part of the PROMEN II study. The inclusion of this study would arti- ficially inflate the size of our meta-analysis and poten- tially bias our results. Thus, only another study, namely our previously conducted case-control study, was included in our meta-analysis. 1 0.90 0.72 0.85 0.55 1 1.00 1.76 1.35 0.26 1 0.82 0.56 0.75 0.30 - 0.33 -2.47 0.25 -2.10 0.50-1.44 - 0.32 - 3.13 0.62 - 4.98 0.80-2.30 - 0.30-2.21 0.19 - 1.68 0.44-1.29 - 0.90 0.69 0.83 0.50 - 1.00 1.73 1.33 0.31 0.80 0.57 0.76 0.31 Figure 1. shows the results of the meta-analysis results. The pooled data are based on 122 Pca patients and 414 controls. The meta-analysis suggested an association between an increased Pca risk and higher urinary levels of 16α-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09- 3.05) and the protective effect of a higher 2-OHE 1to16α- OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31- 0.90). We found no statistically significant results for 2- OHE1. There was no evidence of heterogeneity (I2 = 0, for any of the reported estimates). Discussion The results of this study and meta-analysis suggest that the metabolic pathway favoring 2-hydroxylation over 16α- hydroxylation might be associated with a reduction in Pca risk. While the findings from this case-control study are not statistically significant, they appear consistent with those from a previously conducted, larger case-control study on the protective role of hydroxylated metabolites with virtually no estrogenic activity in the development of Pca [13]. A meta-analysis of the results from these two studies, preceded by a systematic search of the literature showing no additional studies, revealed evidence in sup- port of the study hypothesis. Our study has several strengths. The prospective design allowed for sample collection years before Pca diagnosis. On this basis, it is plausible that the observed differences in urinary levels of estrogen metabolites by case-control status were not biased by any cancer-related hormonal Page 5 of 8 (page number not for citation purposes) 95% CIc - 0.32-2.46 0.23-2.03 0.49-1.42 - 0.32-3.13 0.58-5.14 0.76-2.33 - 0.30-2.17 0.19-1.71 0.44-1.30