Functional polymorphisms in FOXC2 gene and Epithelial ovarian Cancer susceptibility in Chinese population

BACKGROUND: Epithelial ovarian cancer (EOC) is highly lethal gynecological cancer. Forkhead Box Protein C2 (FOXC2) promotes occurrence and development of various malignant tumors. The present study is aimed at exploring the correlation between the polymorphism of FOXC2 and epithelial ovarian cancer susceptibility in Chinese Han population. METHODS: A case-control design was used to verify the association between FOXC2 polymorphisms and epithelial ovarian cancer. The genotyping was performed using Taqman® SNP Genotyping kit by qRT-PCR. The genetic variants including rs3751794 C > T, rs1035550 A > G, rs4843163 C > G and rs4843396 C > T in FOXC2 gene were analyzed. The strength of the associations was detected using odds ratios and 95% confidence intervals. Stratification analyses showed the association between the FOXC2 gene polymorphisms rs3751794 C > T, rs4843163 C > G and rs4843396 C > T with epithelial ovarian cancer susceptibility in terms of age, metastasis status, clinical stage, pathological grade, pregnant times, pausimenia, and the expression of ER, PR, wild p53 and mutant p53. RESULTS: Rs3751794 C > T (P = 0.0016), rs4843163 C > G (P < 0.0001) and rs4843396 C > T (P < 0.0001) were significantly associated with increased epithelial ovarian cancer risk. In stratification analyses,rs3751794 C > T, was identified to be dominant in no metastasis patients, clinical stage 4 group, middle grade pathological stage, pregnant time over 3 patients, post-menopause women, strong wild type p53 expression; rs4843163 C > G was dominant in high grade clinical stage, high grade pathological stage, post-menopause women, strong ER expression group and no mutant p53 expression group; rs4843396 C > T was dominant in high grade clinical stage, high grade pathological stage, strong ER expression group. The rs1035550 A > G was not related to epithelial ovarian cancer susceptibility. CONCLUSIONS: The results of the current study verified that FOXC2 gene polymorphisms were associated with increased epithelial ovarian cancer risk and suggested that FOXC2 gene polymorphisms might be a potential biomarker for epithelial ovarian cancer susceptibility.