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ANO7 is associated with aggressive prostate cancer
Author(s) -
Kaikkonen Elina,
Rantapero Tommi,
Zhang Qin,
Taimen Pekka,
Laitinen Virpi,
Kallajoki Markku,
Jambulingam Dhanaprakash,
Ettala Otto,
Knaapila Juha,
Boström Peter J.,
Wahlström Gudrun,
Sipeky Csilla,
Pursiheimo JuhaPekka,
Tammela Teuvo,
KellokumpuLehtinen PirkkoLiisa,
Fey Vidal,
Maehle Lovise,
Wiklund Fredrik,
Wei GongHong,
Schleutker Johanna
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31746
Subject(s) - prostate cancer , oncology , medicine , cohort , genotype , cancer , prostate , disease , gene , biology , genetics
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.