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

journal contribution
posted on 2023-05-18, 13:58 authored by Liesel FitzgeraldLiesel Fitzgerald, Kumar, A, Boyle, EA, Zhang, Y, McIntosh, LM, Kolb, S, Stott-Miller, M, Smith, T, Karyadi, DM, Ostrander, EA, Hsu, L, Shendure, J, Stanford, JL
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.


Publication title

Cancer Epidemiology, Biomarkers and Prevention










Menzies Institute for Medical Research


Amer Assoc Cancer Research

Place of publication

615 Chestnut St, 17Th Floor, Philadelphia, USA, Pa, 19106-4404

Rights statement

Copyright ?2013 American Association for Cancer Research.

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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