SPINK1 and urinary bladder cancer: For example, hypermethylation of the CpG shore of the Shh gene resulted in Shh loss, and inhibition of DNA methylation increased Shh expression to halt the initiation of bladder cancer at the early stage of progression [48]; DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) was linked to decreased TREX2 gene expression and protein expression, which may affect drug-induced DNA damage repair in laryngeal cancer [49]; and Epigenetic Silencing of miRNA-338-5p and miRNA-421 drived SPINK1-Positive Prostate Cancer [50].