Fitzgerald, LM and Kumar, A and Boyle, EA and Zhang, Y and McIntosh, LM and Kolb, S and Stott-Miller, M and Smith, T and Karyadi, DM and Ostrander, EA and Hsu, L and Shendure, J and Stanford, JL, Germline Missense Variants in the BTNL2 Gene Are Associated with Prostate Cancer Susceptibility, Cancer Epidemiology, Biomarkers and Prevention, 22, (9) pp. 1520-1528. ISSN 1055-9965 (2013) [Refereed Article]
Copyright 2013 American Association for Cancer Research.
METHODS: To identify rare mutations for prostate cancer, we conducted whole-exome sequencing (WES) in multiple kindreds (n = 91) from 19 hereditary prostate cancer (HPC) families characterized by aggressive or early-onset phenotypes. Candidate variants (n = 130) identified through family- and bioinformatics-based filtering of WES data were then genotyped in an independent set of 270 HPC families (n = 819 prostate cancer cases; n = 496 unaffected relatives) for replication. Two variants with supportive evidence were subsequently genotyped in a population-based case-control study (n = 1,155 incident prostate cancer cases; n = 1,060 age-matched controls) for further confirmation. All participants were men of European ancestry.
RESULTS: The strongest evidence was for two germline missense variants in the butyrophilin-like 2 (BTNL2) gene (rs41441651, p.Asp336Asn and rs28362675, p.Gly454Cys) that segregated with affection status in two of the WES families. In the independent set of 270 HPC families, 1.5% (rs41441651; P = 0.0032) and 1.2% (rs28362675; P = 0.0070) of affected men, but no unaffected men, carried a variant. Both variants were associated with elevated prostate cancer risk in the population-based study (rs41441651: OR, 2.7; 95% CI, 1.27-5.87; P = 0.010; rs28362675: OR, 2.5; 95% CI, 1.16-5.46; P = 0.019).
CONCLUSIONS: Results indicate that rare BTNL2 variants play a role in susceptibility to both familial and sporadic prostate cancer.
IMPACT: Results implicate BTNL2 as a novel prostate cancer susceptibility gene.
|Item Type:||Refereed Article|
|Keywords:||Prostate Cancer Next Generation Sequencing|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Oncology and carcinogenesis|
|Research Field:||Cancer genetics|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Fitzgerald, LM (Dr Liesel Fitzgerald)|
|Web of Science® Times Cited:||27|
|Deposited By:||Menzies Institute for Medical Research|
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