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Int J Cancer. 2018 Nov 15;143(10):2479-2487. doi: 10.1002/ijc.31746. Epub 2018 Sep 22.

ANO7 is associated with aggressive prostate cancer.

Author information

1
Institute of Biomedicine, University of Turku, Turku, Finland.
2
Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
3
Biocenter Oulu, University of Oulu, Oulu, Finland.
4
Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
5
Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland.
6
Fimlab Laboratories, Tampere, Finland.
7
Department of Urology, Turku University Hospital, Turku, Finland.
8
Department of Urology, Tampere University Hospital, Tampere, Finland.
9
Department of Oncology, Tampere University Hospital, Tampere, Finland.
10
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
11
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
12
Department of Medical Genetics, TUCH Microbiology and Genetics, Turku University Hospital, Turku, Finland.

Abstract

Prostate cancer is one of the most common and heritable human cancers. Our aim was to find germline biomarkers that can predict disease outcome. We previously detected predisposing signals at 2q37, the location of the prostate specific ANO7 gene. To investigate, in detail, the associations between the ANO7 gene and PrCa risk and disease aggressiveness, ANO7 was sequenced in castration resistant tumors together with samples from unselected PrCa patients and unaffected males. Two pathogenic variants were discovered and genotyped in 1769 patients and 1711 unaffected males. Expression of ANO7 vs. PrCa aggressiveness was investigated. Different databases along with Swedish and Norwegian cohorts were used for validation. Case-control and aggressive vs. nonaggressive association analyses were performed against risk and/or cancer aggressiveness. The ANO7 mRNA level and patient survival were analyzed using expression data from databases. Variant rs77559646 showed both risk (OR 1.40; p = 0.009, 95% CI 1.09-1.78) and association with aggressive PrCa (Genotype test p = 0.04). It was found to be an eQTL for ANO7 (Linear model p-values for Finnish patients p = 0.009; Camcap prostate tumor p = 2.53E-06; Stockholm prostate tumor cohort p = 1.53E-13). rs148609049 was not associated with risk, but was related to shorter survival (HR 1.56; 95% CI 1.03-2.36). High ANO7 expression was independently linked to poor survival (HR 18.4; 95% CI 1.43-237). ANO7 genotypes correlate with expression and biochemical relapse, suggesting that ANO7 is a potential PrCa susceptibility gene and that its elevated expression correlates with disease severity and outcome.

KEYWORDS:

ANO7; CRPC; expression; prostate cancer; survival

PMID:
30157291
DOI:
10.1002/ijc.31746

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