Androgen receptor binding sites enabling genetic prediction of mortality due to prostate cancer in cancer-free subjects.
Loading...
Embargo End Date
ICR Authors
Authors
Ito, S
Liu, X
Ishikawa, Y
Conti, DD
Otomo, N
Kote-Jarai, Z
Suetsugu, H
Eeles, RA
Koike, Y
Hikino, K
Yoshino, S
Tomizuka, K
Horikoshi, M
Ito, K
Uchio, Y
Momozawa, Y
Kubo, M
BioBank Japan Project,
Kamatani, Y
Matsuda, K
Haiman, CA
Ikegawa, S
Nakagawa, H
Terao, C
Liu, X
Ishikawa, Y
Conti, DD
Otomo, N
Kote-Jarai, Z
Suetsugu, H
Eeles, RA
Koike, Y
Hikino, K
Yoshino, S
Tomizuka, K
Horikoshi, M
Ito, K
Uchio, Y
Momozawa, Y
Kubo, M
BioBank Japan Project,
Kamatani, Y
Matsuda, K
Haiman, CA
Ikegawa, S
Nakagawa, H
Terao, C
Document Type
Journal Article
Date
2023-08-23
Date Accepted
2023-06-27
Abstract
Prostate cancer (PrCa) is the second most common cancer worldwide in males. While strongly warranted, the prediction of mortality risk due to PrCa, especially before its development, is challenging. Here, we address this issue by maximizing the statistical power of genetic data with multi-ancestry meta-analysis and focusing on binding sites of the androgen receptor (AR), which has a critical role in PrCa. Taking advantage of large Japanese samples ever, a multi-ancestry meta-analysis comprising more than 300,000 subjects in total identifies 9 unreported loci including ZFHX3, a tumor suppressor gene, and successfully narrows down the statistically finemapped variants compared to European-only studies, and these variants strongly enrich in AR binding sites. A polygenic risk scores (PRS) analysis restricting to statistically finemapped variants in AR binding sites shows among cancer-free subjects, individuals with a PRS in the top 10% have a strongly higher risk of the future death of PrCa (HR: 5.57, Pā=ā4.2 Ć 10-10). Our findings demonstrate the potential utility of leveraging large-scale genetic data and advanced analytical methods in predicting the mortality of PrCa.
Citation
Nature Communications, 2023, 14 (1), pp. 4863 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
2041-1723
2041-1723
2041-1723
2041-1723
Collections
Research Team
Oncogenetics