Cited by 918Genetic Associations and EpidemiologyProstate Cancer Treatment and ResearchProstate Cancer Diagnosis and Treatment

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

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The Profile Study, Schumacher, Fredrick R., Australian Prostate Cancer BioResource (APCB), The IMPACT Study, Canary PASS Investigators, Breast and Prostate Cancer Cohort Consortium (BPC3), The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Cancer of the Prostate in Sweden (CAPS), Prostate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci (PEGASUS), The Genetic Associations and Mechanisms in Oncology (GAME-ON)/Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium, Al Olama, Ali Amin, 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., Gapstur, Susan M., Carter, Brian D., Tangen, Catherine M., Goodman, Phyllis J., Thompson, Ian M., Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Håkansson, Niclas, West, Catharine M. L., Dunning, Alison M., Burnet, Neil, Mucci, Lorelei A., Giovannucci, Edward, Andriole, Gerald L., Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Beane Freeman, Laura E., Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Travis, Ruth C., Key, Tim J., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C., Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., FitzGerald, Liesel M., Kibel, Adam S., Drake, Bettina F., Vega, Ana, Gómez-Caamaño, Antonio, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Penney, Kathryn L., Stampfer, Meir, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Stanford, Janet L., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Ostrander, Elaine A., Geybels, Milan S., Nordestgaard, Børge G., Nielsen, Sune F., Weischer, Maren, Bisbjerg, Rasmus, Røder, Martin Andreas, Iversen, Peter, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Maier, Christiane, Luedeke, Manuel, Schnoeller, Thomas, Kim, Jeri, Logothetis, Christopher J., John, Esther M., Teixeira, Manuel R., Paulo, Paula, Cardoso, Marta, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Lin, Daniel W., Newcomb, Lisa F., Lessel, Davor, Gamulin, Marija, Kulis, Tomislav, Kaneva, Radka, Usmani, Nawaid, Singhal, Sandeep, Slavov, Chavdar, Mitev, Vanio, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, Xu, Jianfeng, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Michael, Agnieszka, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., Lindstrom, Sara, Turman, Constance, Ma, Jing, Hunter, David J., Riboli, Elio, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Hoover, Robert N., Machiela, Mitchell J., Cui, Zuxi, Kraft, Peter, Amos, Christopher I., Conti, David V., Easton, Douglas F., Wiklund, Fredrik, Chanock, Stephen J., Henderson, Brian E., Kote-Jarai, Zsofia, Haiman, Christopher A., Eeles, Rosalind A.·2018·Nature Genetics

DOI 10.1038/s41588-018-0142-8PMC PMC6568012

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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 PrCa 1.

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Yuan, S., Carter, P., Bruzelius, M., Vithayathil, M. K., Kar, S., Mason, A. M., Lin, A., Burgess, S., & Larsson, S. C. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102956 · Cited by 144
Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
Zhang, Y., Hurson, A. N., Zhang, H., Choudhury, P. P., Easton, D. F., Milne, R. L., Simard, J., Hall, P. N., Michailidou, K., Dennis, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16483-3 · Cited by 134
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Evaluating the Utility of Polygenic Risk Scores in Identifying High-Risk Individuals for Eight Common Cancers
Jia, G., Lu, Y., Wen, W., Long, J., Liu, Y., Tao, R., Li, B., Denny, J. C., Shu, X., & Zheng, W. (2020) · JNCI Cancer Spectrum · doi:10.1093/jncics/pkaa021 · Cited by 136
“(16) reported that men in the top 1% of PRS had a relative risk of 5.”
BackgroundSelf-citation
Assessing the causal association of glycine with risk of cardio-metabolic diseases
Wittemans, L. B. L., Lotta, L. A., Oliver‐Williams, C., Stewart, I. D., Surendran, P., Karthikeyan, S., Day, F. R., Koulman, A., Imamura, F., Zeng, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08936-1 · Cited by 132
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Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan
FinnGen, Sakaue, S., Kanai, M., Karjalainen, J. M., Akiyama, M., Kurki, M., Matoba, N., Takahashi, A., Hirata, M., Kubo, M., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0785-8 · Cited by 121
Geographic Variation and Bias in the Polygenic Scores of Complex Diseases and Traits in Finland
Kerminen, S., Martin, A. R., Koskela, J. T., Ruotsalainen, S., Havulinna, A. S., Surakka, I. L., Palotie, A. V., Perola, M., Salomaa, V. V., Daly, M. J., et al. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.05.001 · Cited by 111
Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry
Yuan, J., Kensler, K. H., Hu, Z., Zhang, Y., Zhang, T., Jiang, J., Xu, M., Pan, Y., Long, M., Montone, K. T., et al. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008641 · Cited by 116
Merging new-age biomarkers and nanodiagnostics for precision prostate cancer management
Koo, K. M., Mainwaring, P. N., Tomlins, S. A., & Trau, M. (2019) · Nature Reviews Urology · doi:10.1038/s41585-019-0178-2 · Cited by 109
A transcriptome-wide association study of high-grade serous epithelial ovarian cancer identifies new susceptibility genes and splice variants
Gusev, A., Lawrenson, K., Lin, X., Junior, P. C. M. L., Kar, S., Vavra, K. C., Segato, F., Fonseca, M. A., Lee, J. M., Pejovic, T., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0395-x · Cited by 104
Self-citation
Shared heritability and functional enrichment across six solid cancers
Jiang, X., Finucane, H. K., Schumacher, F. R., Schmit, S. L., Tyrer, J. P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K. B., Dennis, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08054-4 · Cited by 110
Self-citation
Assessment of a Polygenic Risk Score in Screening for Prostate Cancer
McHugh, J. K., Bancroft, E. K., Saunders, E. J., Brook, M. N., McGrowder, E. H., Wakerell, S., James, D., Rageevakumar, R., Benton, B. E., Taylor, N., et al. (2025) · New England Journal of Medicine · doi:10.1056/nejmoa2407934 · Cited by 110
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Post-GWAS in prostate cancer: from genetic association to biological contribution
Farashi, S., Kryza, T., Clements, J. A., & Batra, J. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0087-3 · Cited by 106
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Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
Dadaev, T., Saunders, E. J., Newcombe, P. J., Anokian, E., Leongamornlert, D. A., Brook, M. N., Cieza-Borrella, C., Mijušković, M., Wakerell, S., Olama, A. A. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04109-8 · Cited by 109
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Radiogenomics Consortium Genome-Wide Association Study Meta-Analysis of Late Toxicity After Prostate Cancer Radiotherapy
Kerns, S. L., Fachal, L., Dorling, L., Barnett, G. C., Baran, A., Peterson, D. R., Hollenberg, M., Hao, K., Narzo, A. D., Ahsen, M. E., et al. (2020) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djz075 · Cited by 117
“Germline DNA from whole blood was genotyped for published GWASs (5,10,22–25) using Affymetrix SNP6.”
Self-citation
Dissecting polygenic signals from genome-wide association studies on human behaviour
Abdellaoui, A., & Verweij, K. J. H. (2021) · Nature Human Behaviour · doi:10.1038/s41562-021-01110-y · Cited by 104
Germline Pathogenic Variants in 7636 Japanese Patients With Prostate Cancer and 12 366 Controls
Momozawa, Y., Iwasaki, Y., Hirata, M., Liu, X., Kamatani, Y., Takahashi, A., Sugano, K., Yoshida, T., Murakami, Y., Matsuda, K., et al. (2019) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djz124 · Cited by 104
“Among common cancers at 11 anatomical sites, PCa was found to be the most heritable (2), and genome-wide association studies have identified more than 150 variants associated with PCa (3).”
Background
Cancer PRSweb: An Online Repository with Polygenic Risk Scores for Major Cancer Traits and Their Evaluation in Two Independent Biobanks
Fritsche, L. G., Patil, S. B., Beesley, L. J., VandeHaar, P., Salvatore, M., Ma, Y., Peng, R. B., Taliun, D., Zhou, X., & Mukherjee, B. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.08.025 · Cited by 92
Pesticide exposure and risk of aggressive prostate cancer among private pesticide applicators
Pardo, L. A., Freeman, L. E. B., Lerro, C. C., Andreotti, G., Hofmann, J. N., Parks, C. G., Sandler, D. P., Lubin, J. H., Blair, A. E., & Koutros, S. (2020) · Environmental Health · doi:10.1186/s12940-020-00583-0 · Cited by 97
Self-citation
Liability threshold modeling of case–control status and family history of disease increases association power
Hujoel, M. L. A., Gazal, S., Loh, P., Patterson, N. J., & Price, A. L. (2020) · Nature Genetics · doi:10.1038/s41588-020-0613-6 · Cited by 91
Sex-specific genetic effects across biomarkers
Flynn, E., Tanigawa, Y., Rodríguez, F., Altman, R. B., Sinnott-Armstrong, N., & Rivas, M. A. (2020) · European Journal of Human Genetics · doi:10.1038/s41431-020-00712-w · Cited by 89
A Multiple-Testing Procedure for High-Dimensional Mediation Hypotheses
Dai, J. Y., Stanford, J. L., & LeBlanc, M. L. (2020) · Journal of the American Statistical Association · doi:10.1080/01621459.2020.1765785 · Cited by 90
“The most recent and the largest GWAS assembled 79,194 cases and 61,112 controls of European ancestry from 59 studies, and identified 62 novel loci associated with the overall prostate cancer risk (Schumacher et al. 2018).”
BackgroundInfluentialSelf-citation
Assessing Lung Cancer Absolute Risk Trajectory Based on a Polygenic Risk Model
Hung, R. J., Warkentin, M. T., Brhane, Y., Chatterjee, N., Christiani, D. C., Landi, M. T., Caporaso, N. E., Liu, G., Johansson, M., Albanes, D., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-1237 · Cited by 91
“Yes 3,514 (31) 1,565 (19) 180 (10) 5,311 (2) 196 (10) 2,381 (5) Polygenic Model for Lung Cancer Absolute Risk Trajectory”
Self-citation
Recurrent repeat expansions in human cancer genomes
Erwin, G. S., Gürsoy, G., Al-Abri, R., Suriyaprakash, A., Dolzhenko, E., Zhu, K., Hoerner, C. R., White, S. M., Ramirez, L., Vadlakonda, A., et al. (2022) · Nature · doi:10.1038/s41586-022-05515-1 · Cited by 86
Self-citation
Inferring disease architecture and predictive ability with LDpred2-auto
Privé, F., Albiñana, C., Arbel, J., Paşaniuc, B., & Vilhjálmsson, B. J. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2023.10.010 · Cited by 88
Causal inference for heritable phenotypic risk factors using heterogeneous genetic instruments
Wang, J., Zhao, Q., Bowden, J., Hemani, G., Smith, G. D., Small, D. S., & Zhang, N. R. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009575 · Cited by 85
Identifying and correcting for misspecifications in GWAS summary statistics and polygenic scores
Privé, F., Arbel, J., Aschard, H., & Vilhjálmsson, B. J. (2022) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2022.100136 · Cited by 85
Assessing the causal role of epigenetic clocks in the development of multiple cancers: a Mendelian randomization study
Berstein, F. M., McCartney, D. L., Lu, A. T., Tsilidis, K. K., Bouras, E., Haycock, P., Burrows, K., Phipps, A. I., Buchanan, D. D., Cheng, I. C., et al. (2022) · eLife · doi:10.7554/elife.75374 · Cited by 89
“804 Prostate cancer GWAS summary data were acquired from a Prostate Cancer Association 805 Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) study by 806 Schumacher et al.(72).”
Self-citation
Genome-wide risk prediction of common diseases across ancestries in one million people
Mars, N., Kerminen, S., Feng, Y. A., Kanai, M., Läll, K., Thomas, L. F., Skogholt, A. H., Parolo, P. D. B., Neale, B. M., Smoller, J. W., et al. (2022) · Cell Genomics · doi:10.1016/j.xgen.2022.100118 · Cited by 83
“Compared to the PRSs containing a smaller number of variants, the genome-wide PRSs showed generally better performance and higher transferability to individuals of South Asian and African ancestry.(13,18) The main exception was African ancestry, where the prostate cancer PRS consisting of 269 variants outperformed the…”
Result
Gut microbiota and risk of five common cancers: A univariable and multivariable Mendelian randomization study
Wei, Z., Yang, B., Tang, T., Xiao, Z., Ye, F., Li, X., Wu, S., Huang, J., & Jiang, S. (2023) · Cancer Medicine · doi:10.1002/cam4.5772 · Cited by 80
Germline Sequencing DNA Repair Genes in 5545 Men With Aggressive and Nonaggressive Prostate Cancer
Darst, B. F., Dadaev, T., Saunders, E. J., Sheng, X., Wan, P. C., Pooler, L., Xia, L. Y., Chanock, S. J., Berndt, S. I., Gapstur, S. M., et al. (2020) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djaa132 · Cited by 84
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Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study
Karlsson, Q., Brook, M. N., Dadaev, T., Wakerell, S., Saunders, E. J., Muir, K. R., Neal, D. E., Giles, G. G., MacInnis, R. J., Thibodeau, S. N., et al. (2021) · European Urology Oncology · doi:10.1016/j.euo.2020.12.001 · Cited by 86
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Combined Effect of a Polygenic Risk Score and Rare Genetic Variants on Prostate Cancer Risk
Darst, B. F., Sheng, X., Eeles, R. A., Kote‐Jarai, Z., Conti, D. V., & Haiman, C. A. (2021) · European Urology · doi:10.1016/j.eururo.2021.04.013 · Cited by 78
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Body size and composition and risk of site-specific cancers in the UK Biobank and large international consortia: A mendelian randomisation study
Vithayathil, M. K., Carter, P., Kar, S., Mason, A. M., Burgess, S., & Larsson, S. C. (2021) · PLoS Medicine · doi:10.1371/journal.pmed.1003706 · Cited by 81
“In addition, publicly available data were extracted from the MR-Base platform [30] for lung, breast, ovarian, uterine, and prostate cancer from the International Lung Cancer Consortium (11,348 cases and 15,861 controls) [31], Breast Cancer Association Consortium (BCAC) (122,977 cases and 105,974 controls) [32], the Ov…”
Background
Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors
Mazrooei, P., Kron, K. J., Zhu, Y., Zhou, S., Grillo, G., Mehdi, T., Ahmed, M., Severson, T., Guilhamon, P., Armstrong, N. S., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.005 · Cited by 73
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Intersecting single-cell transcriptomics and genome-wide association studies identifies crucial cell populations and candidate genes for atherosclerosis
Slenders, L., Landsmeer, L. P. L., Cui, K., Depuydt, M. A. C., Verwer, M. C., Mekke, J. M., Timmerman, N., van den Dungen, N. A. M., Kuiper, J., de Winther, M. P. J., et al. (2021) · European Heart Journal Open · doi:10.1093/ehjopen/oeab043 · Cited by 71
African-specific molecular taxonomy of prostate cancer
Jaratlerdsiri, W., Jiang, J., Gong, T., Patrick, S. M., Willet, C. E., Chew, T., Lyons, R. J., Haynes, A., Pasqualim, G., Louw, M., et al. (2022) · Nature · doi:10.1038/s41586-022-05154-6 · Cited by 75
Self-citation
Polygenic hazard score is associated with prostate cancer in multi-ethnic populations
Huynh‐Le, M., Fan, C. C., Karunamuni, R. A., Thompson, W. K., Martı́nez, M. E., Eeles, R. A., Kote‐Jarai, Z., Muir, K. R., collaborators, U., Schleutker, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21287-0 · Cited by 67
Self-citation
CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors identifies repressive chromatin loops
Guo, Y., Perez, A. A., Hazelett, D., Coetzee, G., Rhie, S., & Farnham, P. (2018) · Genome Biology · doi:10.1186/s13059-018-1531-0 · Cited by 71
Polygenic risk modeling for prediction of epithelial ovarian cancer risk
Dareng, E., Tyrer, J. P., Barnes, D. R., Jones, M. R., Yang, X., Aben, K. K. H., Adank, M. A., Agata, S., Andrulis, I. L., Anton‐Culver, H., et al. (2022) · European Journal of Human Genetics · doi:10.1038/s41431-021-00987-7 · Cited by 73
“DISCUSSION Genetic risk profiling with PRSs has led to actionable outcomes for cancers such as breast and prostate [22, 23].”
BackgroundSelf-citation
Mendelian randomization and clinical trial evidence supports TYK2 inhibition as a therapeutic target for autoimmune diseases
Yuan, S., Wang, L., Zhang, H., Xu, F., Zhou, X., Yu, L., Sun, J., Chen, J., Ying, H., Xu, X., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104488 · Cited by 73
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Clinical utility of polygenic risk scores: a critical 2023 appraisal
Koch, S., Schmidtke, J., Krawczak, M., & Caliebe, A. (2023) · Journal of Community Genetics · doi:10.1007/s12687-023-00645-z · Cited by 80
Genome Sequencing during a Patient’s Journey through Cancer
Nangalia, J., & Campbell, P. J. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1910138 · Cited by 66
Vitamin D and overall cancer risk and cancer mortality: a Mendelian randomization study
Ong, J., Gharahkhani, P., An, J., Law, M. H., Whiteman, D. C., Neale, R. Ε., & MacGregor, S. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy307 · Cited by 75
Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan
Hollis, B., Day, F. R., Busch, A. S., Thompson, D. J., Soares, A. G., Timmers, P. R. H. J., Kwong, A. S. F., Easton, D. F., Joshi, P. K., Timpson, N. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14451-5 · Cited by 78
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Recommandations françaises du Comité de cancérologie de l’AFU – actualisation 2020–2022 : cancer de la prostate
Rozet, F., Mongiat-Artus, P., Hennequin, C., Beauval, J., Beuzeboc, P., Cormier, L., Fromont, G., Mathiéu, R., Ploussard, G., Renard‐Penna, R., et al. (2020) · The French Journal of Urology · doi:10.1016/s1166-7087(20)30752-1 · Cited by 79
Self-citation
Hereditary Predisposition to Prostate Cancer: From Genetics to Clinical Implications
Brandão, A., Paulo, P., & Teixeira, M. R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21145036 · Cited by 74
“Overall, large case-control GWAS have uncovered approximately 170 common low-penetrance susceptibility loci (typically, individually ORs < 2) that, in combination, may explain over 30% of the familial relative risk (FRR) of PrCa in European ancestry populations [14,15,125].”
BackgroundSelf-citation
Circulating vitamin C concentration and risk of cancers: a Mendelian randomization study
Fu, Y., Xu, F., Jiang, L., Miao, Z., Liang, X., Yang, J., Larsson, S. C., & Zheng, J. (2021) · BMC Medicine · doi:10.1186/s12916-021-02041-1 · Cited by 73
“We retrieved publicly available summary-level data of 140,254 participants of European ancestry (79,148 prostate cancer cases and 61, 106 controls) from a meta-analysis of 8 GWASs included in the PRACTICAL consortium [29].”
Method
Genetically proxied therapeutic inhibition of antihypertensive drug targets and risk of common cancers: A mendelian randomization analysis
Yarmolinsky, J., Díez‐Obrero, V., Richardson, T. G., Pigeyre, M., Sjaarda, J., Paré, G., Walker, V. M., Vincent, E. E., Tan, V. Y., Obón‐Santacana, M., et al. (2022) · PLoS Medicine · doi:10.1371/journal.pmed.1003897 · Cited by 71
“Summary genetic association estimates for overall and advanced prostate cancer risk in up to 79,148 cases and 61,106 controls were obtained from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium [40].”
MethodSelf-citation
Association between circulating vitamin E and ten common cancers: evidence from large-scale Mendelian randomization analysis and a longitudinal cohort study
Xin, J., Jiang, X., Ben, S., Yuan, Q., Su, L., Zhang, Z., Christiani, D. C., Du, M., & Wang, M. (2022) · BMC Medicine · doi:10.1186/s12916-022-02366-5 · Cited by 73
Genome-wide germline correlates of the epigenetic landscape of prostate cancer
Houlahan, K. E., Shiah, Y.-J., Gusev, A., Yuan, J., Ahmed, M., Shetty, A. H., Ramanand, S. G., Yao, C. Q., Bell, C. A., O’Connor, E. P., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0579-z · Cited by 67
Self-citation
Polygenic risk score association with multiple sclerosis susceptibility and phenotype in Europeans
Shams, H., Shao, X., Santaniello, A., Kirkish, G., Harroud, A., Ma, Q., Isobe, N., Alexander, J., Bove, R. M., Baranzini, S. E., et al. (2022) · Brain · doi:10.1093/brain/awac092 · Cited by 75

Authors: Study, T. P., Schumacher, F. R., (APCB), A. P. C. B., Study, T. I., Canary PASS Investigators, Breast and Prostate Cancer Cohort Consortium (BPC3), The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, (CAPS), C. O. T. P. I. S., Prostate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci (PEGASUS), The Genetic Associations and Mechanisms in Oncology (GAME-ON)/Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium, Al Olama, A. A., Berndt, S. I., Benlloch, S., Ahmed, M., Saunders, E. J., Dadaev, T., Leongamornlert, D., Anokian, E., Cieza-Borrella, C., Goh, C., Brook, M. N., Sheng, X., Fachal, L., Dennis, J., Tyrer, J., Muir, K., Lophatananon, A., Stevens, V. L., Gapstur, S. M., Carter, B. D., Tangen, C. M., Goodman, P. J., Thompson, I. M., Batra, J., Chambers, S., Moya, L., Clements, J., Horvath, L., Tilley, W., Risbridger, G. P., Gronberg, H., Aly, M., Nordström, T., Pharoah, P., Pashayan, N., Schleutker, J., Tammela, T. L. J., Sipeky, C., Auvinen, A., Albanes, D., Weinstein, S., Wolk, A., Håkansson, N., West, C. M. L., Dunning, A. M., Burnet, N., Mucci, L. A., Giovannucci, E., Andriole, G. L., Cussenot, O., Cancel-Tassin, G., Koutros, S., Beane Freeman, L. E., Sorensen, K. D., Orntoft, T. F., Borre, M., Maehle, L., Grindedal, E. M., Neal, D. E., Donovan, J. L., Hamdy, F. C., Martin, R. M., Travis, R. C., Key, T. J., Hamilton, R. J., Fleshner, N. E., Finelli, A., Ingles, S. A., Stern, M. C., Rosenstein, B. S., Kerns, S. L., Ostrer, H., Lu, Y.-J., Zhang, H.-W., Feng, N., Mao, X., Guo, X., Wang, G., Sun, Z., Giles, G. G., Southey, M. C., MacInnis, R. J., FitzGerald, L. M., Kibel, A. S., Drake, B. F., Vega, A., Gómez-Caamaño, A., Szulkin, R., Eklund, M., Kogevinas, M., Llorca, J., Castaño-Vinyals, G., Penney, K. L., Stampfer, M., Park, J. Y., Sellers, T. A., Lin, H.-Y., Stanford, J. L., Cybulski, C., Wokolorczyk, D., Lubinski, J., Ostrander, E. A., Geybels, M. S., Nordestgaard, B. G., Nielsen, S. F., Weischer, M., Bisbjerg, R., Røder, M. A., Iversen, P., Brenner, H., Cuk, K., Holleczek, B., Maier, C., Luedeke, M., Schnoeller, T., Kim, J., Logothetis, C. J., John, E. M., Teixeira, M. R., Paulo, P., Cardoso, M., Neuhausen, S. L., Steele, L., Ding, Y. C., De Ruyck, K., De Meerleer, G., Ost, P., Razack, A., Lim, J., Teo, S.-H., Lin, D. W., Newcomb, L. F., Lessel, D., Gamulin, M., Kulis, T., Kaneva, R., Usmani, N., Singhal, S., Slavov, C., Mitev, V., Parliament, M., Claessens, F., Joniau, S., Van den Broeck, T., Larkin, S., Townsend, P. A., Aukim-Hastie, C., Gago-Dominguez, M., Castelao, J. E., Martinez, M. E., Roobol, M. J., Jenster, G., van Schaik, R. H. N., Menegaux, F., Truong, T., Koudou, Y. A., Xu, J., Khaw, K.-T., Cannon-Albright, L., Pandha, H., Michael, A., Thibodeau, S. N., McDonnell, S. K., Schaid, D. J., Lindstrom, S., Turman, C., Ma, J., Hunter, D. J., Riboli, E., Siddiq, A., Canzian, F., Kolonel, L. N., Le Marchand, L., Hoover, R. N., Machiela, M. J., Cui, Z., Kraft, P., Amos, C. I., Conti, D. V., Easton, D. F., Wiklund, F., Chanock, S. J., Henderson, B. E., Kote-Jarai, Z., Haiman, C. A., & Eeles, R. A.
Affiliations: Case Western Reserve University (US)
University of Cambridge (GB)
Division of Cancer Epidemiology and Genetics (US)
Institute of Cancer Research (GB)
University of Manchester (GB)
American Cancer Society (US)
Griffith University (AU)
Translational Research Institute (AU)
Garvan Institute of Medical Research (AU)
Karolinska University Hospital (SE)
University of Turku (FI)
Tampere University (FI)
Karolinska Institutet (SE)
Uppsala University (SE)
Harvard University (US)
Washington University in St. Louis (US)
Aarhus University Hospital (DK)
Oslo University Hospital (NO)
Aarhus University (DK)
Princess Margaret Cancer Centre (CA)
University of Oxford (GB)
Albert Einstein College of Medicine (US)
Queen Mary University of London (GB)
Second Military Medical University (CN)
Nanjing Medical University (CN)
Shanghai Medical College of Fudan University (CN)
Cancer Council Victoria (AU)
Brigham and Women's Hospital (US)
The University of Melbourne (AU)
Monash Health (AU)
University of Tasmania (AU)
Universitat Pompeu Fabra (ES)
Fundación Pública Galega de Medicina Xenómica (ES)
Universidad de Cantabria (ES)
Moffitt Cancer Center (US)
National Institutes of Health (US)
University of Washington (US)
University of Copenhagen (DK)
Copenhagen University Hospital (DK)
German Cancer Research Center (DE)
Herlev Hospital (DK)
The University of Texas MD Anderson Cancer Center (US)
Cancer Prevention Institute of California (US)
Universidade do Porto (PT)
Instituto Português de Oncologia Francisco Gentil (PT)
Ghent University (BE)
Ghent University Hospital (BE)
University of Malaya (MY)
University Hospital Centre Zagreb (HR)
University of Alberta (CA)
Alexandrovska Hospital (BG)
Southampton General Hospital (GB)
University of Surrey (GB)
Universitair Ziekenhuis Leuven (BE)
Manchester Academic Health Science Centre (GB)
Inserm (FR)
Endeavor Health (US)
Mayo Clinic (US)
USC Norris Comprehensive Cancer Center (US)
Dartmouth College (US)
Royal Marsden NHS Foundation Trust (GB)
Corresponding author: Schumacher, Fredrick R.
Eeles, Rosalind A.
ORCID: Schumacher, Fredrick R.
Berndt, Sonja I.
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.
Gapstur, Susan M.
Carter, Brian D.
Tangen, Catherine M.
Goodman, Phyllis J.
Thompson, Ian M.
Batra, Jyotsna
Chambers, Suzanne
Moya, Leire
Clements, Judith
Horvath, Lisa
Tilley, Wayne
Risbridger, Gail P.
Aly, Markus
Nordström, Tobias
Pharoah, Paul
Pashayan, Nora
Schleutker, Johanna
Tammela, Teuvo L. J.
Sipeky, Csilla
Auvinen, Anssi
Albanes, Demetrius
Weinstein, Stephanie
Wolk, Alicja
Håkansson, Niclas
West, Catharine M. L.
Dunning, Alison M.
Burnet, Neil
Mucci, Lorelei A.
Giovannucci, Edward
Andriole, Gerald L.
Cussenot, Olivier
Koutros, Stella
Borre, Michael
Grindedal, Eli Marie
Neal, David E.
Donovan, Jenny L.
Hamdy, Freddie C.
Martin, Richard M.
Travis, Ruth C.
Hamilton, Robert J.
Fleshner, Neil E.
Finelli, Antonio
Ingles, Sue Ann
Stern, Mariana C.
Rosenstein, Barry S.
Kerns, Sarah L.
Lu, Yong-Jie
Zhang, Hong-Wei
Feng, Ninghan
Mao, Xueying
Wang, Guomin
Giles, Graham G.
Southey, Melissa C.
MacInnis, Robert J.
FitzGerald, Liesel M.
Kibel, Adam S.
Drake, Bettina F.
Vega, Ana
Szulkin, Robert
Eklund, Martin
Kogevinas, Manolis
Llorca, Javier
Penney, Kathryn L.
Stampfer, Meir
Park, Jong Y.
Sellers, Thomas A.
Lin, Hui-Yi
Stanford, Janet L.
Cybulski, Cezary
Ostrander, Elaine A.
Nordestgaard, Børge G.
Nielsen, Sune F.
Weischer, Maren
Bisbjerg, Rasmus
Røder, Martin Andreas
Iversen, Peter
Brenner, Hermann
Holleczek, Bernd
Kim, Jeri
Logothetis, Christopher J.
John, Esther M.
Teixeira, Manuel R.
Paulo, Paula
Cardoso, Marta
Neuhausen, Susan L.
Steele, Linda
Ding, Yuan Chun
Ost, Piet
Razack, Azad
Lim, Jasmine
Teo, Soo-Hwang
Lin, Daniel W.
Lessel, Davor
Gamulin, Marija
Kaneva, Radka
Usmani, Nawaid
Singhal, Sandeep
Slavov, Chavdar
Mitev, Vanio
Parliament, Matthew
Claessens, Frank
Joniau, Steven
Townsend, Paul A.
Castelao, Jose Esteban
Roobol, Monique J.
Jenster, Guido
van Schaik, Ron H. N.
Truong, Thérèse
Xu, Jianfeng
Khaw, Kay-Tee
Pandha, Hardev
Michael, Agnieszka
Thibodeau, Stephen N.
McDonnell, Shannon K.
Schaid, Daniel J.
Turman, Constance
Ma, Jing
Siddiq, Afshan
Canzian, Federico
Kolonel, Laurence N.
Hoover, Robert N.
Machiela, Mitchell J.
Cui, Zuxi
Kraft, Peter
Amos, Christopher I.
Conti, David V.
Easton, Douglas F.
Wiklund, Fredrik
Chanock, Stephen J.
Haiman, Christopher A.
Eeles, Rosalind A.
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2018-06-11
Volume: 50
Issue: 7
Pages: 928-936
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/s41588-018-0142-8
PMC: PMC6568012
OpenAlex: W2806504012
Cited by: 902
References: 65
Citations by year: 2026: 53 · 2025: 96 · 2024: 133 · 2023: 123 · 2022: 151 · 2021: 132 · 2020: 104 · 2019: 79 · 2018: 30
FWCI: 52.93
Type: journal article
Language: en
Update notices: correction (2019-01-08)
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
St George's Online Research Archive (St George's University of London) (acceptedVersion)
QUT ePrints (Queensland University of Technology) (submittedVersion)
Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
Civil War Book Review (submittedVersion)
eCite Digital Repository (University of Tasmania) (submittedVersion)
UTAS Research Repository (submittedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
HAL (submittedVersion, other-oa)
Ghent University Academic Bibliography (Ghent University) (submittedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
ePrints Soton (University of Southampton) (submittedVersion)
UCL Discovery (University College London) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
Figshare (submittedVersion)
Lirias (submittedVersion)
UTS ePRESS (University of Technology Sydney) (submittedVersion)
Research Explorer (The University of Manchester) (submittedVersion)
Bristol Research (University of Bristol) (submittedVersion, other-oa)
Griffith Research Online (submittedVersion)
Spiral (Imperial College London) (submittedVersion)
Apollo (University of Cambridge) (submittedVersion)
Apollo
Funders: U.S. Department of Defense (C5047/A10692, C1287/A10118, C5047/A7357, W81XWH, C1287/A16563, C8197/A16565, C1281/A12014, C5047/A8384, C12292/A11174, C5047/A15007, CA128978, W81XWH1010341, 223175)
Cancer Research Institute
Prostate Cancer Foundation
Breast Cancer Research Foundation (C5047/A10692, C5047/A15007, C1287/A10118, CA128978, 209057, C1287/A16563, W81XWH-10-1-0341, C8197/A16565, C5047/A8384, C1281/A12014, 396414, C12292/A11174, HEALTH-F2-2009-223175)
Ovarian Cancer Research Fund (W81XWH-10-1-0341, C1281/A12014, C1287/A10118, C8197/A16565, C12292/A11174, CA128978, C5047/A10692, C5047/A15007, C1287/A16563, C5047/A8384, HEALTH-F2-2009-223175)
University of Southern California (C1281/A12014, C5047/A10692, C8197/A16565, C1287/A10118, C12292/A11174, C5047/A8384, W81XWH-10-1-0341, C5047/A15007, CA128978, C1287/A16563, HEALTH-F2-2009-223175)
Aarhus Universitet
Aarhus Universitetshospital
Case Western Reserve University
Harvard T.H. Chan School of Public Health
Institut for Klinisk Medicin, Aarhus Universitet
National Cancer Research Institute
Royal Marsden NHS Foundation Trust
Australian Prostate Cancer Research
Cancer Research UK (C8197/A16565’, 223175, C1281/A12014, 10119, C5047/A7357, C5047/A15007’, C1287‐A10118, 12014, HEALTHF2-2009-223175, C5047/A3354, 21332, 16561, 16565, C12292/A11174, ‘C5047/A10692, 15007, C1287, C5047/A8384, 10118, 14136, 16563, 18504, 16491, 17528, C16913-A6135, CA128978, A16563, 19169, C1287-A10710, W81XWH-10-1-0341, C1287‐A16563, C1281)
National Institute for Health and Care Research (C5047/A15007, W81XWH-10-1-0341, NF-SI-0510-10096, C8197/A16565, HEALTH-F2-2009-223175, NF-SI-0509-10242, CA128978, C1287/A10118, C1281/A12014, NF-SI-0512-10114, C5047/A10692, NF-SI-0513-10121, C1287/A16563, C12292/A11174, C5047/A8384)
University of Cambridge
University of Warwick
University College London
University of Oxford
European Commission (C1287/A10118, W81XWH-10-1-0341, C1281/A12014, C1287/A16563, C5047/A10692, C5047/A8384, C12292/A11174, C5047/A15007, C8197/A16565, CA128978, 223175)
University of Bristol
Prostate Cancer Foundation of Australia
Monash University
Griffith University
Queensland University of Technology
Cambridge University Hospitals
Karolinska Institutet (W81XWH-10-1-0341, C1281/A12014, C1287/A10118, HEALTH-F2-2009-223175, C1287/A16563, CA128978, C5047/A8384, C5047/A10692, C12292/A11174, C8197/A16565, C5047/A15007)
Peter MacCallum Cancer Centre
Tampereen Yliopisto
Turun Yliopisto
Uppsala Universitet
Tays
Turun Yliopistollinen Keskussairaala
National Institutes of Health (C1281/A12014, 223175, W81XWH-10-1-0341, C8197/A16565, C5047/A7357, C12292/A11174, C1287/A16563, W81XWH, C1287/A10118, HHSN268201200008I, C5047/A10692, HEALTH-F2-2009-223175, C5047/A15007, C5047/A8384, X01HG007492)
Canadian Institutes of Health Research (C5047/A8384, C5047/A15007, C5047/A10692, C1287/A10118, C1287/A16563, CA128978, C8197/A16565, C1281/A12014, C12292/A11174, W81XWH-10-1-0341, HEALTH-F2-2009-223175, 223175)
Medical Research Council (C12292/A11174, C1281/A12014, CA128978, C5047/A8384, HEALTH-F2-2009-223175, C8197/A16565, W81XWH-10-1-0341, C1287/A16563, C5047/A10692, MR/N003284/1, C1287/A10118, C5047/A15007)
National Health and Medical Research Council (623204, 504702, 126402, 614296, 251533, 504700, 504715)
Cancer Council Victoria (C1287/A16563, C1287/A10118, C8197/A16565, HEALTH-F2-2009-223175, C1281/A12014, C5047/A15007, C12292/A11174, W81XWH-10-1-0341, CA128978, C5047/A10692, C5047/A8384)
Cancer Council Queensland
Warwick Medical School
Servicio Gallego de Salud
Monash Biomedicine Discovery Institute, Monash University
National Heart, Lung, and Blood Institute (HHSN268201200008I, HHSN268201200008C)
National Cancer Institute (R01CA128978, U01CA188392, C5047/A15007, C5047/A10692, C5047/A8384, U19CA148065, HEALTH-F2-2009-223175, W81XWH-10-1-0341, UM1CA182883, UG1CA189974, U01CA098710, U19CA148537, K05CA175147, CA148065, U01CA098216, C1281/A12014, C12292/A11174, U01CA098758, U19CA148112, (CA128978, C1287/A16563, K07CA187546, C1287/A10118, C8197/A16565, U01CA098233, U10CA037429)
Division of Cancer Epidemiology and Genetics, National Cancer Institute
DOD Prostate Cancer Research Program
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
Health Sciences › Medicine › Urology › Prostate Cancer Diagnosis and Treatment
Keywords: prostate cancer, cancer susceptibility loci, genetic association, early-onset prostate cancer, polygenic risk score, ATM, p27, European ancestry, risk prediction, fine mapping
MeSH terms: Genotype, Humans, Male, Prostatic Neoplasms, Risk, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Loci

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

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