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Cancer Epidemiol Biomarkers Prev. 2013 Sep;22(9):1520-8. doi: 10.1158/1055-9965.EPI-13-0345. Epub 2013 Jul 5.

Germline missense variants in the BTNL2 gene are associated with prostate cancer susceptibility.

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1
Division of Public Health Sciences, University of Washington, Seattle, Washington, USA.

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.

PMID:
23833122
PMCID:
PMC3769499
DOI:
10.1158/1055-9965.EPI-13-0345
[Indexed for MEDLINE]
Free PMC Article
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