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Laitinen, Virpi H.; Akinrinade, Oyediran; Rantapero, Tommi; Tammela, Teuvo L.J.; Wahlfors, Tiina; Schleutker, Johanna
The Prostate, February 15, 2016, Letnik: 76, Številka: 3Journal Article
BACKGROUND The inherited factors that predispose individuals to prostate cancer (PrCa) remain largely unknown. The aim of this study was to identify germline copy number variants (CNVs) in Finnish individuals that could contribute to an increased PrCa risk. METHODS Genome‐wide CNV screening was performed by analyzing single nucleotide polymorphisms from 105 PrCa patients and 37 unaffected relatives, representing 31 Finnish hereditary PrCa (HPC) families. The CNVs that aggregated in affected individuals and overlapped with genes implicated in cancer were validated using quantitative PCR in 189 index patients from Finnish HPC families and in 476 controls. RESULTS An intronic deletion (14.7 kb) in the EPHA3 gene coding for class A ephrin receptor was observed in 11.6% of PrCa patients and in 6.1% of controls. The deletion associated with an increased PrCa risk (P = 0.018, OR = 2.06, 95%CI = 1.18–3.61). Although incomplete segregation with affection status was observed, the results show that the deletion was overrepresented in PrCa patients (56.1%) when compared to unaffected male relatives (31.2%). Interestingly, PrCa‐specific mortality was higher among EPHA3 deletion carriers (24.3%) than among patients with a normal EPHA3 copy number (3.4%). CONCLUSIONS This study is the first investigation of the contribution of germline CNVs to HPC susceptibility in Finland. A novel association between the EPHA3 deletion and PrCa risk was observed and, if confirmed, screening for this variant may aid in risk stratification among HPC patients. Prostate 76:316–324, 2016. © 2015 Wiley Periodicals, Inc.
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