BACKGROUND: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI=1.0-1.4, P(trend) = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1.1-1.5, P(trend) = 0.003). METHODS: We sought to replicate this association in 12 other studies comprising 4,482 cases and 6,894 controls of white non-Hispanic ancestry in the Ovarian Cancer Association Consortium. RESULTS: No evidence for an association with all cancers or serous cancers was observed in a combined analysis of data from the replication studies (all: OR = 1.0, 95% CI = 0.9-1.1, P(trend) = 0.61; serous: OR = 1.0, 95% CI = 0.9-1.1, P(trend) = 0.85) or from the combined analysis of discovery and replication studies (all: OR = 1.0, 95% CI = 1.0-1.1, P(trend) = 0.28; serous: OR = 1.1, 95% CI = 1.0-1.2, P(trend) = 0.11). There was no evidence for statistical heterogeneity in ORs across the studies. CONCLUSIONS: Although rs2660753 is a strong prostate cancer susceptibility polymorphism, the association with another hormonally related cancer, invasive EOC, is not supported by this replication study. Impact: Our findings, based on a larger sample size, emphasize the importance of replicating potentially promising genetic risk associations. Cancer Epidemiol Biomarkers Prev; 20(5); 1028-31. ©2011 AACR.