In conclusion, by using a two‐stage study and bioinformatics analyses, we have identified that rs643555C > T acts as a risk factor of prostate cancer recurrence through increasing expression of CDH2. Our study provides new insights into the genetic variants in cell adhesion pathways underlying disease progression, and may offer a prognostic biomarker to the personalized management of prostate cancer. This evidence concerns the gene CDH2 and Familial prostate cancer.