Journal Article

Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Vega, Ana, Hamilton, Robert J., Cybulski, Cezary, Geybels, Milan S., Weischer, Maren, Mitev, Vanio, Aukim-Hastie, Claire, Sun, Zan, Rosenstein, Barry S., Razack, Azad, Cardoso, Marta, Steele, Linda, Stern, Mariana C., FitzGerald, Liesel M., Cannon-Albright, Lisa, Travis, Ruth C., Kibel, Adam S., Khaw, Kay-Tee, Teixeira, Manuel R., Nordström, Tobias, Hamdy, Freddie C., Teo, Soo-Hwang, Benlloch, Sara, Van den Broeck, Thomas, De Ruyck, Kim, Wolk, Alicja, Schleutker, Johanna, Donovan, Jenny L., Tyrer, Jonathan, Mucci, Lorelei A., Ahmed, Mahbubl, Kraft, Peter, Maehle, Lovise, Gapstur, Susan M., Drake, Bettina F., Orntoft, Torben Falck, Bisbjerg, Rasmus, Parliament, Matthew, Sheng, Xin, Feng, Ninghan, Iversen, Peter, Berndt, Sonja I., Giles, Graham G., Kerns, Sarah L., Wokolorczyk, Dominika, Thibodeau, Stephen N., Canzian, Federico, Gamulin, Marija, Zhang, Hong-Wei, Andriole, Gerald L., Wang, Guomin, Fachal, Laura, Park, Jong Y., Stanford, Janet L., Kaneva, Radka, Koutros, Stella, Logothetis, Christopher J., Conti, David V., Ostrander, Elaine A., McDonnell, Shannon K., Haiman, Christopher A., Auvinen, Anssi, Niel

2018

Overview

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 PrCa 1 . A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 38/43 / 45/43 / 631/208/205 / 692/308/174 / 692/699/67/589/466 / Agriculture / Animal Genetics and Genomics / Associations / Biology / Biomedical and Life Sciences / Biomedicine / Cancer Research / Case studies / Case-Control Studies / Confidence intervals / Consortia / Data processing / Disease susceptibility / Family medical history / Gene Function / Gene mapping / Genealogy / Genetic aspects / Genetic Loci / Genetic Predisposition to Disease / Genetic research / Genome-wide association studies / Genome-Wide Association Study - methods / Genomes / Genomics / Genotype / Genotypes / Glycine / Health aspects / Health risk assessment / Human Genetics / Humans / Letter / Life Sciences / Loci / Male / Mapping / Medical schools / Men / Meta-analysis / Neurophysiology / Polymorphism, Single Nucleotide / Prostate cancer / Prostatic Neoplasms - genetics / Risk / Risk factors / Signal transduction / Software