University of Oulu

Kaikkonen, E. , Rantapero, T. , Zhang, Q. , Taimen, P. , Laitinen, V. , Kallajoki, M. , Jambulingam, D. , Ettala, O. , Knaapila, J. , Boström, P. J., Wahlström, G. , Sipeky, C. , Pursiheimo, J. , Tammela, T. , Kellokumpu‐Lehtinen, P. , , , Fey, V. , Maehle, L. , Wiklund, F. , Wei, G. and Schleutker, J. (2018), ANO7 is associated with aggressive prostate cancer. Int. J. Cancer, 143: 2479-2487. doi:10.1002/ijc.31746

ANO7 is associated with aggressive prostate cancer

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Author: Kaikkonen, Elina1; Rantapero, Tommi2; Zhang, Qin3,4;
Organizations: 1Institute of Biomedicine, University of Turku, Turku, Finland
2Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
3Biocenter Oulu, University of Oulu, Oulu, Finland
4Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
5Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland
6Fimlab Laboratories, Tampere, Finland
7Department of Urology, Turku University Hospital, Turku, Finland
8Department of Urology, Tampere University Hospital, Tampere, Finland
9Department of Oncology, Tampere University Hospital, Tampere, Finland
10Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
11Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
12Department of Medical Genetics, TUCH Microbiology and Genetics, Turku University Hospital, Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.9 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019070422771
Language: English
Published: John Wiley & Sons, 2018
Publish Date: 2019-07-04
Description:

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.

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Series: International journal of cancer
ISSN: 0020-7136
ISSN-E: 1097-0215
ISSN-L: 0020-7136
Volume: 143
Issue: 10
Pages: 2479 - 2487
DOI: 10.1002/ijc.31746
OADOI: https://oadoi.org/10.1002/ijc.31746
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: The Sigrid Juselius Foundation and the Research Funding of Turku University Hospital; Grant sponsor: The Academy of Finland; Grant numbers: #251074 JS; #284618 and #279760; Grant sponsor: The Finnish Cancer Organizations; Grant sponsor: Worldwide Cancer Research; Grant numbers: 14-0089.
Academy of Finland Grant Number: 284618
279760
Detailed Information: 284618 (Academy of Finland Funding decision)
279760 (Academy of Finland Funding decision)
Copyright information: © 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
  https://creativecommons.org/licenses/by-nc-nd/4.0/