Abstract Several single nucleotide polymorphisms (SNPs) in lin-28B, a gene encoding RNA binding protein that represses miRNA let-7 maturation and acts as an oncogene, were found in the genome-wide association studies (GWAS), to be associated with the risk of ovarian cancer and cancer-related risk factors such as age at menarche, body mass index (BMI) and height. However, whether these SNPs are functionally important and can serve as prognostic markers in ovarian cancer remain unknown. The purposes of this study were to investigate the genotype-phenotype relationship in lin-28B and their associations with patient survivals in epithelial ovarian cancer. To achieve these purposes, we analyzed five lin-28B SNPs using Taqman® assays and lin-28B expression using SYBR green-based qPCR in tumor samples collected from 211 patients diagnosed with primary epithelial ovarian cancer. Wilcoxon rank sum test was performed to analyze cis-regulatory eQTL; Kaplan-Meir survival curves and Cox proportional hazards regression models were used to assess the associations of lin-28B SNPs and expression with the risks of relapse and death. The results showed that three SNPs (rs314276, rs314277 and rs7759938) were associated with lin-28B mRNA levels. Using mfold, rs314276 and rs314277 were predicted to affect the secondary structures of lin-28B mRNA. SNP rs7759938 is located at the 500 bp downstream of the region with H3K4Me1 (an enhancer marker) enrichment restricted to stem cells. However, these SNPs were not significantly associated with clinical and pathological parameters including disease stage, tumor grade, histological types, residual tumor size, and debulking results. No SNPs alone were related to patient survivals. Among patients initially responding to chemotherapy, those with high lin-28B expression had higher risks of death (hazard ratio (HR)=3.27, 95% CI: 1.63-6.56), and relapse (HR=2.53, 95% CI: 1.41-4.54) than those with low one. After adjustment for patient age at surgery, disease stage, tumor grade, histological types and residual tumor size, the associations were still statistically significant. These findings suggest that 3 of the GWAS-hit SNPs in lin-28B may affect gene expression, but these SNPs are not associated with ovarian cancer survival. The results also indicate that lin-28B may affect the outcome of chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3655. doi:1538-7445.AM2012-3655