Germline copy number variation analysis in Finnish families with hereditary prostate cancer.
Prostate
; 76(3): 316-24, 2016 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-26552734
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
Receptor Protein-Tyrosine Kinases
/
Germ-Line Mutation
/
Genetic Predisposition to Disease
/
White People
/
DNA Copy Number Variations
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
Prostate
Year:
2016
Document type:
Article
Affiliation country:
Finland