Three (rs1477908+ rs1387665, rs1467251+ rs7625555, and rs1824717+ rs7625555) were in the gene pair of MMP16 and ROBO1. The interaction of rs1401862 and rs6964705 was in the MMP16 and EGFR, and another SNP pair of rs2176771 and rs333970 was in the MMP16 and CSF1. With the exception of the SNP pair of rs1477908 and rs1387665, additional two SNP pairs (rs1467251+ rs7625555 and rs1824717+ rs7625555) in the gene pair of MMP16 and ROBO1 were associated with prostate cancer aggressiveness. This evidence concerns the gene MMP16 and prostate cancer.