Functional variants of the <i>chitinase 3‐like 1</i> gene are associated with clinicopathologic outcomes and progression of prostate cancer

<jats:title>Abstract</jats:title><jats:p>Chitinase 3‐like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in advanced stages of several cancer types, including prostate cancer (PCa). Impacts of genetic variants of <jats:italic>CHI3L1</jats:italic> on PCa development have not yet been investigated. The most common well‐studied genetic variations are single‐nucleotide polymorphisms (SNPs). Therefore, the objective of this study was to explore associations of <jats:italic>CHI3L1</jats:italic> SNPs with both the susceptibility to PCa and its clinicopathological development. Three promoter SNPs, rs6691378 (−1371, G>A), rs10399805 (−247, G>A) and rs4950928 (−131, C>G), and one non‐synonymous SNP, rs880633 (+2950, T>C), were analysed using a TaqMan allelic discrimination assay for genotyping in a cohort of 701 PCa patients and 701 healthy controls. Results indicated that there were no significant associations of PCa susceptibility with these four <jats:italic>CHI3L1</jats:italic> SNPs. However, among elderly PCa patients (aged >65 years), it was observed that polymorphic variants (GA + AA) of <jats:italic>CHI3L1</jats:italic> rs6691378 and 10399805 were significantly linked to reduced risks of several clinicopathological characteristics, including a high Gleason grade, advanced pathologic T stage and tumour cell invasion. Moreover, analyses of The Cancer Genome Atlas database revealed that <jats:italic>CHI3L1</jats:italic> expression levels were elevated in PCa tissues compared with normal tissues. Interestingly, higher <jats:italic>CHI3L1</jats:italic> expression levels were found to be associated with longer progression‐free survival rates in PCa patients. Our findings indicated that levels of CHI3L1 may influence the progression of PCa, and the rs6691378 and 10399805 SNP genetic variants of <jats:italic>CHI3L1</jats:italic> are linked to the clinicopathological development of PCa within a Taiwanese population.</jats:p>