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Abstract: Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P?5.0?×?10-8) with PrCa and one locus significantly associated with early-onset PrCa (?55 years). Our findings include missense variants rs1800057 (odds ratio (OR)?=?1.16; P?=?8.2?×?10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR?=?1.06; P?=?2.3?×?10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk?=?2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk?=?5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.
Fuente: Nat Genet. 2018 Jul;50(7):928-936
Editorial: Nature Publishing Group
Año de publicación: 2018
Nº de páginas: 13
Tipo de publicación: Artículo de Revista
DOI: 10.1038/s41588-018-0142-8
ISSN: 1061-4036,1546-1718
Url de la publicación: https://doi.org/10.1038/s41588-018-0142-8
Leer publicación
SCHUMACHER, FREDRICK R.
OLAMA, ALI AMIN AL
BERNDT, SONJA I.
BENLLOCH, SARA
AHMED, MAHBUBL
SAUNDERS, EDWARD J.
DADAEV, TOKHIR
LEONGAMORNLERT, DANIEL
ANOKIAN, EZEQUIEL
CIEZA-BORRELLA, CLARA
GOH, CHEE
BROOK, MARK N.
SHENG, XIN
FACHAL, LAURA
DENNIS, JOE
TYRER, JONATHAN
MUIR, KENNETH
LOPHATANANON, ARTITAYA
STEVENS, VICTORIA L.
FRANCISCO JAVIER LLORCA DIAZ
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