A significant proportion of men develop prostate cancer (PrCa) during their lifetime,

which causes challenges for public health. PSA (prostate-specific antigen) screening

studies have shown that testing all men at specific ages causes overdiagnosis of PrCa

and unnecessary treatments for individuals who have indolent disease. Additional

methods are required alongside PSA testing to be able to prognosticate the disease

outcome and to focus the treatments on aggressive PrCa cases. The chromosomal

location 2q37.3, where the transmembrane protein coding gene anoctamin 7 (ANO7)

resides, is associated with PrCa susceptibility in linkage analyses and genome-wide

association studies (GWAS). In addition, ANO7 has been considered to be expressed

specifically in prostate tissue, and it has been suggested as a target for PrCa

immunotherapy.

This thesis work concentrates on investigating the role of ANO7 in PrCa. ANO7

expression was significantly higher in prostate tissue than in any other tissue type,

and ANO7 expression was elevated in PrCa compared to benign tissue. Moreover,

elevated expression was associated with poor survival among patients. Nextgeneration

sequencing (NGS) analysis of the ANO7 gene revealed possible

truncating rare germline variants, which were found only in PrCa patients and not in

controls in the initial screening. These variants were genotyped from several

different PrCa patient cohorts and sets of unaffected males. The stop-gain variant in

exon 1 was associated with poor survival, and the variant in intron/exon 4 was

associated with aggressive disease. Because the intron/exon 4 variant was related to

aggressive cancer but not to poor survival, we investigated whether the variant

carriers would have a good response to docetaxel treatment in castration-resistant

PrCa. As was hypothesized, the variant carriers had a better response to docetaxel

than the non-carriers. When investigating ANO7 protein interactions, we observed

an enrichment specifically in proteins related to vesicle trafficking. This study

indicates that ANO7 has a role in PrCa development and that truncating mutations

in the gene predispose patients to aggressive PrCa. The variants reported in this study

could facilitate precision medicine for PrCa patient care.