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 tumours 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. non-aggressive association analyses were performed against risk and/or cancer aggressiveness. The ANO7 mRNA level and patient survival were analysed 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 tumour p=2.53E-06; Stockholm prostate tumour 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. This article is protected by copyright. All rights reserved.
International journal of cancer. 2018 Aug 29 [Epub ahead of print]
Elina Kaikkonen, Tommi Rantapero, Qin Zhang, Pekka Taimen, Virpi Laitinen, Markku Kallajoki, Dhanaprakash Jambulingam, Otto Ettala, Juha Knaapila, Peter J Boström, Gudrun Wahlström, Csilla Sipeky, Juha-Pekka Pursiheimo, Teuvo Tammela, Pirkko-Liisa Kellokumpu-Lehtinen, PRACTICAL Consortium , Vidal Fey, Lovise Maehle, Fredrik Wiklund, Gong-Hong Wei, Johanna Schleutker
Institute of Biomedicine, University of Turku, Turku, Finland., Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland., Biocenter Oulu, University of Oulu, Oulu, Finland., Fimlab Laboratories, Tampere, Finland., Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland., Department of Urology, Turku University Hospital, Turku, Finland., Department of Medical Genetics, Oslo University Hospital, Oslo, Norway., Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm 10435, Sweden.