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Germline Missense Variants in the BTNL2 Gene Are Associated with Prostate Cancer Susceptibility

Citation

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 Statement

Copyright 2013 American Association for Cancer Research.

DOI: doi:10.1158/1055-9965.EPI-13-0345

Abstract

BACKGROUND: Rare, inherited mutations account for 5% to 10% of all prostate cancer cases. However, to date, few causative mutations have been identified.

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 Details

Item Type:Refereed Article
Keywords:Prostate Cancer Next Generation Sequencing
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Genetics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Fitzgerald, LM (Dr Liesel Fitzgerald)
ID Code:104104
Year Published:2013
Web of Science® Times Cited:18
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-11-03
Last Modified:2017-11-06
Downloads:0

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