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830 results on '"Rosenstein, Barry"'

105. A first radiotherapy application of functional bulboclitoris anatomy, a novel female sexual organ-at-risk, and organ-sparing feasibility study

Author

Marshall, Deborah C, primary, Ghiassi-Nejad, Zahra, additional, Powers, Allison, additional, Reidenberg, Joy S, additional, Argiriadi, Pamela, additional, Ru, Meng, additional, Dumane, Vishruta, additional, Buckstein, Michael, additional, Goodman, Karyn, additional, Blank, Stephanie V, additional, Schnur, Julie, additional, and Rosenstein, Barry, additional

Published
2021
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108. G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor

Author

Brandão, Andreia, Paulo, Paula, Maia, Sofia, Pinheiro, Manuela, Peixoto, Ana, Cardoso, Marta, Silva, Maria P., Santos, Catarina, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth, Collaborators, UKGPCS Collaborators UKGPCS, Schleutker, Johanna, Wang, Ying, Pashayan, Nora, Batra, Jyotsna, BioResource, APCB BioResource APCB, Grönberg, Henrik, Neal, David E., Nordestgaard, Børge G., Tangen, Catherine M., Southey, Melissa C., Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A., Travis, Ruth C., Stanford, Janet L., Mucci, Lorelei A., West, Catharine M. L., Nielsen, Sune F., Kibel, Adam S., Cussenot, Olivier, Berndt, Sonja I., Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Park, Jong Y., Ingles, Sue A., Maier, Christiane, Hamilton, Robert J., Rosenstein, Barry S., Vega, Ana, Collaborators, The IMPACT Study Steering Committee and Collaborators The IMPACT Study Steering Committee and, Kogevinas, Manolis, Wiklund, Fredrik, Penney, Kathryn L., Brenner, Hermann, John, Esther M., Kaneva, Radka, Logothetis, Christopher J., Neuhausen, Susan L., Ruyck, Kim De, Razack, Azad, Newcomb, Lisa F., Investigators, Canary PASS Investigators Canary PASS, Lessel, Davor, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A., Roobol, Monique J., Committee, The Profile Study Steering Committee The Profile Study Steering, Consortium, The PRACTICAL Consortium The PRACTICAL, and Teixeira, Manuel R.

Subjects
founder variant, cancer predisposition, prostate cancer, CHEK2
Abstract

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A&gt, G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case&ndash, control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A&gt, G was found significantly associated with an increased risk for PrCa (OR 1.9, 95% CI: 1.1&ndash, 3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A&gt, G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

Published
2020
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109. An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

Author

Wu, Lang, Yang, Yaohua, Guo, Xingyi, Shu, Xiao-Ou, Cai, Qiuyin, Shu, Xiang, Li, Bingshan, Tao, Ran, Wu, Chong, Nikas, Jason B., Sun, Yanfa, Zhu, Jingjing, Brenner, Hermann, John, Esther M., Clements, Judith, Grindedal, Eli Marie, Stanford, Janet L., Kote-Jarai, Zsofia, Haiman, Christopher A., Zheng, Wei, Long, Jirong, Eeles, Rosalind A., Henderson, Brian E., Schumacher, Fredrick R., Easton, Douglas, Benlloch, Sara, Olama, Ali Amin Al, Muir, Kenneth, Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Gapstur, Susan M., Stevens, Victoria L., Tangen, Catherine M., Batra, Jyotsna, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Géraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Cybulski, Cezary, Nordestgaard, Børge G., Maier, Christiane, Kim, Jeri, Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Gamulin, Marija, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Dominguez, Manuela Gago, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Blot, William J., Riboli, Elio, Li, Bingshan [0000-0003-2129-168X], Wu, Chong [0000-0002-8400-1785], Nikas, Jason B. [0000-0001-9703-0422], Roobol, Monique J. [0000-0001-6967-1708], Giles, Graham G. [0000-0003-4946-9099], Park, Jong Y. [0000-0002-6384-6447], Eeles, Rosalind A. [0000-0002-3698-6241], Zheng, Wei [0000-0003-1226-070X], and Apollo - University of Cambridge Repository

Subjects
631/208, 631/67/68, article, 631/67/2324, urologic and male genital diseases
Abstract

It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes.

Published
2020
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110. Runs of homozygosity and testicular cancer risk

Author

Loveday, C, Sud, A, Litchfield, K, Levy, M, Holroyd, A, Broderick, P, Kote-Jarai, Z, Dunning, AM, Muir, K, Peto, J, Eeles, R, Easton, DF, Dudakia, D, Orr, N, Pashayan, N, Rustin, Gordon, Srihari, Narayanan N, Cole, David, Askill, Colin, Bertelli, Gianfilippo, Barber, James, Gilby, Ed, White, Jeff, Baybrooke, Jeremy, Leahy, Michael, Welch, Richard, Chakraborti, Prabir, Joffe, Johnathan, Brown, Richard, Faust, Guy, Simmonds, Peter, Mazhar, Danish, Stockdale, Andrew, Hrounda, David, Humber, Caroline, Appel, Wiebke, Hong, Anne, Howard, Grahame, Douglas, Fiona, Bloomfield, David, Butt, Mohammad, Kelly, Kay, Mehra, Rakesh, Rogers, Paul, Hatton, Matthew, Hennig, Ivo, McAteer, John, Savage, Philip, Seckl, Michael, Gale, Joanna, Clark, Peter, Woby, Steve, Rathmell, Adrian, Lamont, Alan, Sarwar, Naveed, Stuart, Nick, Chowdhury, Simon, Beesley, Sharon, Winkler, Mathius, Hamid, Abdel, Pathak, Sanjeev, Madhavan, Krishnaswamy, Highley, Martin, Money-Kryle, Julian, Brock, Cathryn, Sreenivasan, Thiagarajan, Henderson, Brian E, Haiman, Christopher A, Schumacher, Fredrick R, Al Olama, Ali Amin, Benlloch, Sara, Berndt, Sonja I, Conti, David V, Wiklund, Fredrik, Chanock, Stephen, Gapster, Susan, Stevens, Victoria L, Tangen, Catherine M, Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Schleutker, Johanna, Albanes, Demetrius, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Geraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, Maehle, Lovise, Neal, David E, Hamdy, Freddie C, Donovan, Jenny L, Travis, Ruth C, Hamilton, Robert J, Ingles, Sue Ann, Rosenstein, Barry S, Lu, Yong-Jie, Giles, Graham G, Kibel, Adam S, Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L, Park, Jong Y, Stanford, Janet L, Cybulski, Cezary, Nordestgaard, Borge G, Brenner, Hermann, Maier, Christiane, Kim, Jeri, John, Esther M, Teixeira, Manuel R, Neuhausen, Susan L, De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F, Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A, Dominguez, Manuela Gago, Roobol, Monique J, Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albrigh, Lisa, Pandha, Hardev, Thibodeau, Stephen N, Reid, A, Huddart, RA, Houlston, RS, Turnbull, C, and Urology

Subjects
Oncology, Male, Endocrinology, Diabetes and Metabolism, LOCI, Genome-wide association study, Runs of Homozygosity, SUSCEPTIBILITY, VARIANTS, 0302 clinical medicine, Endocrinology, testicular germ cell tumour, Risk Factors, Genotype, genetics, Andrology, 030219 obstetrics & reproductive medicine, Genome, Homozygote, Neoplasms, Germ Cell and Embryonal, Disease gene identification, homozygosity mapping, Life Sciences & Biomedicine, RECENT POSITIVE SELECTION, medicine.medical_specialty, Urology, Biology, BREAST, Polymorphism, Single Nucleotide, 03 medical and health sciences, Endocrinology & Metabolism, Testicular Neoplasms, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Genetic predisposition, cancer, Humans, Allele, GENOME-WIDE ASSOCIATION, SEX DETERMINATION, runs of homozygosity, Science & Technology, IDENTIFICATION, Cancer, recessive, medicine.disease, GERM-CELL TUMOR, CONSANGUINITY, Reproductive Medicine, Relative risk, genome-wide association studies, Genome-Wide Association Study
Abstract

BACKGROUND: Testicular germ cell tumour (TGCT) is highly heritable but > 50% of the genetic risk remains unexplained. Epidemiological observation of greater relative risk to brothers of men with TGCT compared to sons has long alluded to recessively acting TGCT genetic susceptibility factors, but to date none have been reported. Runs of homozygosity (RoH) are a signature indicating underlying recessively acting alleles and have been associated with increased risk of other cancer types. OBJECTIVE: To examine whether RoH are associated with TGCT risk. METHODS: We performed a genome-wide RoH analysis using GWAS data from 3206 TGCT cases and 7422 controls uniformly genotyped using the OncoArray platform. RESULTS: Global measures of homozygosity were not significantly different between cases and controls, and the frequency of individual consensus RoH was not significantly different between cases and controls, after correction for multiple testing. RoH at three regions, 11p13-11p14.3, 5q14.1-5q22.3 and 13q14.11-13q.14.13, were, however, nominally statistically significant at p

Published
2019
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111. Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan

Author

Hollis, Ben, Day, Felix R., Busch, Alexander S., Thompson, Deborah J., Soares, Ana Luiza G., Timmers, Paul R.H.J., Kwong, Alex, Easton, Doug F., Joshi, Peter K., Timpson, Nicholas J., Eeles, Rosalind A., Henderson, Brian E., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Olama, Ali Amin Al, Benlloch, Sara, Muir, Kenneth, Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Gapstur, Susan, Stevens, Victoria L., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Géraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Nordestgaard, Børge G., Day, Felix R [0000-0003-3789-7651], Busch, Alexander S [0000-0003-4417-569X], Thompson, Deborah J [0000-0003-1465-5799], Soares, Ana Luiza G [0000-0003-2763-4647], Timmers, Paul R H J [0000-0002-5197-1267], Kwong, Alex [0000-0003-1953-2771], Easton, Doug F [0000-0003-2444-3247], Joshi, Peter K [0000-0002-6361-5059], Timpson, Nicholas J [0000-0002-7141-9189], Ong, Ken K [0000-0003-4689-7530], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Male, Time Factors, General Physics and Astronomy, Physiology, Genome-wide association study, Genome-wide association studies, Cohort Studies, 0302 clinical medicine, Endocrinology, Genetics research, Sexual Maturation, Young adult, lcsh:Science, RISK, Multidisciplinary, Age Factors, Mendelian Randomization Analysis, Effective sample size, Multidisciplinary Sciences, Pituitary hormones, Science & Technology - Other Topics, Female, Adult, Science, Longevity, Reproductive biology, Biology, Health outcomes, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, MENARCHE, 03 medical and health sciences, Young Adult, AGE, Mendelian randomization, Humans, Hair Color, Genetic association, Menarche, Science & Technology, MUTATIONS, Puberty, General Chemistry, 030104 developmental biology, METASTASIS, PIGMENTATION, lcsh:Q, 030217 neurology & neurosurgery, SKIN, Genome-Wide Association Study
Abstract

The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes., Age at voice-breaking is used to determine puberty timing in men, recall of which is considered less accurate than age at first menarche in women. Here, the authors perform multi-trait GWAS for male puberty timing by including both age at voice breaking and age of first facial hair for improved phenotype definition and power.

Published
2020
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112. Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer

Author

Karunamuni, Roshan A., Huynh-Le, Minh Phuong, Fan, Chun C., Thompson, Wesley, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth, Lophatananon, Artitaya, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, Grönberg, Henrik, Walsh, Eleanor I., Turner, Emma L., Lane, Athene, Martin, Richard M., Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Nordestgaard, Børge G., Tangen, Catherine M., MacInnis, Robert J., Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A., Travis, Ruth C., Stanford, Janet L., Mucci, Lorelei A., West, Catharine M.L., Nielsen, Sune F., Kibel, Adam S., Wiklund, Fredrik, Cussenot, Olivier, Berndt, Sonja I., Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Park, Jong Y., Ingles, Sue A., Maier, Christiane, Hamilton, Robert J., Rosenstein, Barry S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Teixeira, Manuel R., Brenner, Hermann, John, Esther M., Kaneva, Radka, Logothetis, Christopher J., Neuhausen, Susan L., Razack, Azad, Newcomb, Lisa F., Gamulin, Marija, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A., Roobol, Monique J., Zheng, Wei, Mills, Ian G., Andreassen, Ole A., Dale, Anders M., Seibert, Tyler M., other, and, Karunamuni, Roshan A., Huynh-Le, Minh Phuong, Fan, Chun C., Thompson, Wesley, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth, Lophatananon, Artitaya, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, Grönberg, Henrik, Walsh, Eleanor I., Turner, Emma L., Lane, Athene, Martin, Richard M., Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Nordestgaard, Børge G., Tangen, Catherine M., MacInnis, Robert J., Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A., Travis, Ruth C., Stanford, Janet L., Mucci, Lorelei A., West, Catharine M.L., Nielsen, Sune F., Kibel, Adam S., Wiklund, Fredrik, Cussenot, Olivier, Berndt, Sonja I., Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Park, Jong Y., Ingles, Sue A., Maier, Christiane, Hamilton, Robert J., Rosenstein, Barry S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Teixeira, Manuel R., Brenner, Hermann, John, Esther M., Kaneva, Radka, Logothetis, Christopher J., Neuhausen, Susan L., Razack, Azad, Newcomb, Lisa F., Gamulin, Marija, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A., Roobol, Monique J., Zheng, Wei, Mills, Ian G., Andreassen, Ole A., Dale, Anders M., Seibert, Tyler M., and other, and

Abstract

Background: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). Materials and method: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy. Results: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer. Conclusions: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

Published
2021

113. Polygenic hazard score is associated with prostate cancer in multi-ethnic populations

Author

Huynh-Le, Minh Phuong, Fan, Chun Chieh, Karunamuni, Roshan, Thompson, Wesley K., Martinez, Maria Elena, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, Grönberg, Henrik, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nielsen, Sune F., Nordestgaard, Børge G., Wiklund, Fredrik, Tangen, Catherine M., Giles, Graham G., Wolk, Alicja, Albanes, Demetrius, Travis, Ruth C., Blot, William J., Zheng, Wei, Sanderson, Maureen, Stanford, Janet L., Mucci, Lorelei A., West, Catharine M.L., Kibel, Adam S., Cussenot, Olivier, Berndt, Sonja I., Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Menegaux, Florence, Khaw, Kay Tee, Park, Jong Y., Ingles, Sue A., Maier, Christiane, Hamilton, Robert J., Thibodeau, Stephen N., Rosenstein, Barry S., Lu, Yong Jie, Watya, Stephen, Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Huff, Chad, Teixeira, Manuel R., Multigner, Luc, Leach, Robin J., Cannon-Albright, Lisa, Brenner, Hermann, John, Esther M., Kaneva, Radka, Logothetis, Christopher J., Neuhausen, Susan L., De Ruyck, Kim, Pandha, Hardev, Razack, Azad, Newcomb, Lisa F., Fowke, Jay H., Gamulin, Marija, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A., Bush, William S., Roobol, Monique J., Parent, Marie Élise, Hu, Jennifer J., Mills, Ian G., Andreassen, Ole A., Dale, Anders M., Seibert, Tyler M., other, and, Huynh-Le, Minh Phuong, Fan, Chun Chieh, Karunamuni, Roshan, Thompson, Wesley K., Martinez, Maria Elena, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, Grönberg, Henrik, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nielsen, Sune F., Nordestgaard, Børge G., Wiklund, Fredrik, Tangen, Catherine M., Giles, Graham G., Wolk, Alicja, Albanes, Demetrius, Travis, Ruth C., Blot, William J., Zheng, Wei, Sanderson, Maureen, Stanford, Janet L., Mucci, Lorelei A., West, Catharine M.L., Kibel, Adam S., Cussenot, Olivier, Berndt, Sonja I., Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Menegaux, Florence, Khaw, Kay Tee, Park, Jong Y., Ingles, Sue A., Maier, Christiane, Hamilton, Robert J., Thibodeau, Stephen N., Rosenstein, Barry S., Lu, Yong Jie, Watya, Stephen, Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Huff, Chad, Teixeira, Manuel R., Multigner, Luc, Leach, Robin J., Cannon-Albright, Lisa, Brenner, Hermann, John, Esther M., Kaneva, Radka, Logothetis, Christopher J., Neuhausen, Susan L., De Ruyck, Kim, Pandha, Hardev, Razack, Azad, Newcomb, Lisa F., Fowke, Jay H., Gamulin, Marija, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A., Bush, William S., Roobol, Monique J., Parent, Marie Élise, Hu, Jennifer J., Mills, Ian G., Andreassen, Ole A., Dale, Anders M., Seibert, Tyler M., and other, and

Abstract

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10−180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

Published
2021

114. Publisher Correction : Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Author

Conti, David V, Darst, Burcu F, Moss, Lilit C, Saunders, Edward J, Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R, Olama, Ali Amin Al, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N, Sahimi, Ali, Hoffmann, Thomas J, Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Schleutker, Johanna, Tammela, Teuvo L J, Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, Cybulski, Cezary, Wokołorczyk, Dominika, Lubiński, Jan, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Nordestgaard, Børge G, Nielsen, Sune F, Weischer, Maren, Bojesen, Stig E, Røder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A, Tilley, Wayne, Risbridger, Gail P, Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M, Ghoussaini, Maya, Travis, Ruth C, Key, Tim J, Riboli, Elio, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J, Mucci, Lorelei A, Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J, Penney, Kathryn L, Turman, Constance, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L, Ostrander, Elaine A, Geybels, Milan S, Koutros, Stella, Freeman, Laura E Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L, Hoover, Robert N, Machiela, Mitchell J, Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J, Zheng, Wei, Yeboah, Edward D, Mensah, James E, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N, McDonnell, Shannon K, Schaid, Daniel J, West, Catharine M L, Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S, Drake, Bettina F, Cussenot, Olivier, Cancel-Tassin, Géraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M, Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A, Stern, Mariana C, Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S, Kerns, Sarah L, Ostrer, Harry, Teixeira, Manuel R, Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T, Fontham, Elizabeth T H, Mohler, James, Taylor, Jack A, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C, Huff, Chad D, Strom, Sara S, Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J, Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai-Uwe, Klein, Eric A, Hsing, Ann W, Kittles, Rick A, Murphy, Adam B, Logothetis, Christopher J, Kim, Jeri, Neuhausen, Susan L, Steele, Linda, Ding, Yuan Chun, Isaacs, William B, Nemesure, Barbara, Hennis, Anselm J M, Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F, Lin, Daniel W, Fowke, Jay H, Neslund-Dudas, Christine, Rybicki, Benjamin A, Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A, Aukim-Hastie, Claire, Bush, William S, Aldrich, Melinda C, Crawford, Dana C, Srivastava, Shiv, Cullen, Jennifer C, Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J, Jenster, Guido, van Schaik, Ron H N, Hu, Jennifer J, Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja I, Van Den Eeden, Stephen K, Easton, Douglas F, Chanock, Stephen J, Cook, Michael B, Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S, Eeles, Rosalind A, Kote-Jarai, Zsofia, Haiman, Christopher A, Conti, David V, Darst, Burcu F, Moss, Lilit C, Saunders, Edward J, Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R, Olama, Ali Amin Al, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N, Sahimi, Ali, Hoffmann, Thomas J, Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Schleutker, Johanna, Tammela, Teuvo L J, Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, Cybulski, Cezary, Wokołorczyk, Dominika, Lubiński, Jan, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Nordestgaard, Børge G, Nielsen, Sune F, Weischer, Maren, Bojesen, Stig E, Røder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A, Tilley, Wayne, Risbridger, Gail P, Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M, Ghoussaini, Maya, Travis, Ruth C, Key, Tim J, Riboli, Elio, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J, Mucci, Lorelei A, Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J, Penney, Kathryn L, Turman, Constance, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L, Ostrander, Elaine A, Geybels, Milan S, Koutros, Stella, Freeman, Laura E Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L, Hoover, Robert N, Machiela, Mitchell J, Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J, Zheng, Wei, Yeboah, Edward D, Mensah, James E, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N, McDonnell, Shannon K, Schaid, Daniel J, West, Catharine M L, Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S, Drake, Bettina F, Cussenot, Olivier, Cancel-Tassin, Géraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M, Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A, Stern, Mariana C, Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S, Kerns, Sarah L, Ostrer, Harry, Teixeira, Manuel R, Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T, Fontham, Elizabeth T H, Mohler, James, Taylor, Jack A, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C, Huff, Chad D, Strom, Sara S, Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J, Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai-Uwe, Klein, Eric A, Hsing, Ann W, Kittles, Rick A, Murphy, Adam B, Logothetis, Christopher J, Kim, Jeri, Neuhausen, Susan L, Steele, Linda, Ding, Yuan Chun, Isaacs, William B, Nemesure, Barbara, Hennis, Anselm J M, Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F, Lin, Daniel W, Fowke, Jay H, Neslund-Dudas, Christine, Rybicki, Benjamin A, Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A, Aukim-Hastie, Claire, Bush, William S, Aldrich, Melinda C, Crawford, Dana C, Srivastava, Shiv, Cullen, Jennifer C, Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J, Jenster, Guido, van Schaik, Ron H N, Hu, Jennifer J, Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja I, Van Den Eeden, Stephen K, Easton, Douglas F, Chanock, Stephen J, Cook, Michael B, Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S, Eeles, Rosalind A, Kote-Jarai, Zsofia, and Haiman, Christopher A

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2021
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115. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Author

Conti, David, V, Darst, Burcu F., Moss, Lilit C., Saunders, Edward J., Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R., Al Olama, Ali Amin, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Sahimi, Ali, Hoffmann, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R., Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Roder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A., Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Ian M., Jr., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Parent, Marie-Elise, Stanford, Janet L., Ostrander, Elaine A., Geybels, Milan S., Koutros, Stella, Freeman, Laura E. Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sorensen, Karina Dalsgaard, Borre, Michael, Blot, William J., Zheng, Wei, Yeboah, Edward D., Mensah, James E., Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M. L., Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Geraldine, Menegaux, Florence, Truong, Therese, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana, Gomez-Caamano, Antonio, Fachal, Laura, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R., Paulo, Paula, Brandao, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T., Fontham, Elizabeth T. H., Mohler, James, Taylor, Jack A., Kogevinas, Manolis, Llorca, Javier, Castano-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai-Uwe, Klein, Eric A., Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J. M., Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F., Lin, Daniel W., Fowke, Jay H., Neslund-Dudas, Christine, Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer C., Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Hu, Jennifer J., Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja, I, Van den Eeden, Stephen K., Easton, Douglas F., Chanock, Stephen J., Cook, Michael B., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Eeles, Rosalind A., Kote-Jarai, Zsofia, Haiman, Christopher A., Conti, David, V, Darst, Burcu F., Moss, Lilit C., Saunders, Edward J., Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R., Al Olama, Ali Amin, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Sahimi, Ali, Hoffmann, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R., Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Roder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A., Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Ian M., Jr., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Parent, Marie-Elise, Stanford, Janet L., Ostrander, Elaine A., Geybels, Milan S., Koutros, Stella, Freeman, Laura E. Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sorensen, Karina Dalsgaard, Borre, Michael, Blot, William J., Zheng, Wei, Yeboah, Edward D., Mensah, James E., Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M. L., Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Geraldine, Menegaux, Florence, Truong, Therese, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana, Gomez-Caamano, Antonio, Fachal, Laura, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R., Paulo, Paula, Brandao, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T., Fontham, Elizabeth T. H., Mohler, James, Taylor, Jack A., Kogevinas, Manolis, Llorca, Javier, Castano-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai-Uwe, Klein, Eric A., Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J. M., Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F., Lin, Daniel W., Fowke, Jay H., Neslund-Dudas, Christine, Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer C., Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Hu, Jennifer J., Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja, I, Van den Eeden, Stephen K., Easton, Douglas F., Chanock, Stephen J., Cook, Michael B., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Eeles, Rosalind A., Kote-Jarai, Zsofia, and Haiman, Christopher A.

Abstract

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries., Correction in: Nature Genetics https://doi.org/10.1038/s41588-020-00748-0, published online 4 January 2021.In the version of this article originally published, the names of the equally contributing authors and jointly supervising authorswere switched. The correct affiliations are: “These authors contributed equally: David V. Conti, Burcu F. Darst. These authors jointlysupervised this work: David V. Conti, Rosalind A. Eeles, Zsofia Kote-Jarai, Christopher A. Haiman.” The error has been corrected in theHTML and PDF versions of the article.Published online: 20 January 2021https://doi.org/10.1038/s41588-021-00786-2

Published
2021
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121. A Deep Learning Approach Validates Genetic Risk Factors for Late Toxicity After Prostate Cancer Radiotherapy in a REQUITE Multi-National Cohort

Author

Massi, Michela Carlotta, primary, Gasperoni, Francesca, additional, Ieva, Francesca, additional, Paganoni, Anna Maria, additional, Zunino, Paolo, additional, Manzoni, Andrea, additional, Franco, Nicola Rares, additional, Veldeman, Liv, additional, Ost, Piet, additional, Fonteyne, Valérie, additional, Talbot, Christopher J., additional, Rattay, Tim, additional, Webb, Adam, additional, Symonds, Paul R., additional, Johnson, Kerstie, additional, Lambrecht, Maarten, additional, Haustermans, Karin, additional, De Meerleer, Gert, additional, de Ruysscher, Dirk, additional, Vanneste, Ben, additional, Van Limbergen, Evert, additional, Choudhury, Ananya, additional, Elliott, Rebecca M., additional, Sperk, Elena, additional, Herskind, Carsten, additional, Veldwijk, Marlon R., additional, Avuzzi, Barbara, additional, Giandini, Tommaso, additional, Valdagni, Riccardo, additional, Cicchetti, Alessandro, additional, Azria, David, additional, Jacquet, Marie-Pierre Farcy, additional, Rosenstein, Barry S., additional, Stock, Richard G., additional, Collado, Kayla, additional, Vega, Ana, additional, Aguado-Barrera, Miguel Elías, additional, Calvo, Patricia, additional, Dunning, Alison M., additional, Fachal, Laura, additional, Kerns, Sarah L., additional, Payne, Debbie, additional, Chang-Claude, Jenny, additional, Seibold, Petra, additional, West, Catharine M. L., additional, and Rancati, Tiziana, additional

Published
2020
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123. Radiogenomics Consortium Genome-Wide Association Study Meta-Analysis of Late Toxicity After Prostate Cancer Radiotherapy

Author

Kerns, Sarah L, Fachal, Laura, Dorling, Leila, Barnett, Gillian C, Baran, Andrea, Peterson, Derick R, Hollenberg, Michelle, Hao, Ke, Narzo, Antonio Di, Ahsen, Mehmet Eren, Pandey, Gaurav, Bentzen, Søren M, Janelsins, Michelle, Elliott, Rebecca M, Pharoah, Paul D P, Burnet, Neil G, Dearnaley, David P, Gulliford, Sarah L, Hall, Emma, Sydes, Matthew R, Aguado-Barrera, Miguel E, Gómez-Caamaño, Antonio, Carballo, Ana M, Peleteiro, Paula, Lobato-Busto, Ramón, Stock, Richard, Stone, Nelson N, Ostrer, Harry, Usmani, Nawaid, Singhal, Sandeep, Tsuji, Hiroshi, Imai, Takashi, Saito, Shiro, Eeles, Rosalind, DeRuyck, Kim, Parliament, Matthew, Dunning, Alison M, Vega, Ana, Rosenstein, Barry S, West, Catharine M L, Wilson, Leila [0000-0003-1214-8080], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], and Apollo - University of Cambridge Repository

Subjects
Urologic Diseases, 0604 Genetics, Aging, Biomedical, Prevention, Prostate Cancer, Human Genome, Articles, Clinical Medicine and Science, Clinical Research, Genetics, 2.1 Biological and endogenous factors, 1112 Oncology and Carcinogenesis, Patient Safety, Cancer, Biotechnology
Abstract

Background A total of 10%–20% of patients develop long-term toxicity following radiotherapy for prostate cancer. Identification of common genetic variants associated with susceptibility to radiotoxicity might improve risk prediction and inform functional mechanistic studies. Methods We conducted an individual patient data meta-analysis of six genome-wide association studies (n = 3871) in men of European ancestry who underwent radiotherapy for prostate cancer. Radiotoxicities (increased urinary frequency, decreased urinary stream, hematuria, rectal bleeding) were graded prospectively. We used grouped relative risk models to test associations with approximately 6 million genotyped or imputed variants (time to first grade 2 or higher toxicity event). Variants with two-sided Pmeta less than 5 × 10−8 were considered statistically significant. Bayesian false discovery probability provided an additional measure of confidence. Statistically significant variants were evaluated in three Japanese cohorts (n = 962). All statistical tests were two-sided. Results Meta-analysis of the European ancestry cohorts identified three genomic signals: single nucleotide polymorphism rs17055178 with rectal bleeding (Pmeta = 6.2 × 10−10), rs10969913 with decreased urinary stream (Pmeta = 2.9 × 10−10), and rs11122573 with hematuria (Pmeta = 1.8 × 10−8). Fine-scale mapping of these three regions was used to identify another independent signal (rs147121532) associated with hematuria (Pconditional = 4.7 × 10−6). Credible causal variants at these four signals lie in gene-regulatory regions, some modulating expression of nearby genes. Previously identified variants showed consistent associations (rs17599026 with increased urinary frequency, rs7720298 with decreased urinary stream, rs1801516 with overall toxicity) in new cohorts. rs10969913 and rs17599026 had similar effects in the photon-treated Japanese cohorts. Conclusions This study increases the understanding of the architecture of common genetic variants affecting radiotoxicity, points to novel radio-pathogenic mechanisms, and develops risk models for testing in clinical studies. Further multinational radiogenomics studies in larger cohorts are worthwhile.

Published
2020

124. Benzo[a]pyrene enhances the formation of 8-hydroxy-2'-deoxyguanosine by ultraviolet A radiation in calf thymus DNA and human epidermoid carcinoma cells

Author

Liu, Zhisong, Lu, Yuhun, Rosenstein, Barry, Lebwohl, Mark, and Wei, Huachen

Subjects
DNA damage -- Research, Ultraviolet radiation -- Research, Oxidation-reduction reaction -- Research, Guanosine -- Research, Biological sciences, Chemistry
Abstract

The ability of benzo[a]pyrene (BaP) and ultraviolet (UV) radiation to synergistically induce oxidative DNA damage was examined. Results showed that although BaP significantly enhanced 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation was significantly enhanced in the presence UVA, 8-OHdG level was only slightly increased in UVB. However, a direct correlation between 8-OHdG formation and UV dose and BaP concentration was also observed.

Published
1998

127. The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor

Author

Brandão, Andreia, Paulo, Paula, Maia, Sofia, Pinheiro, Manuela, Peixoto, Ana, Cardoso, Marta, Silva, Maria P., Santos, Catarina, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth, Ukgpcs Collaborators, Schleutker, Johanna, Wang, Ying, Pashayan, Nora, Batra, Jyotsna, Apcb BioResource, Grönberg, Henrik, Neal, David E., Nordestgaard, Børge G., Tangen, Catherine M., Southey, Melissa C., Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A., Travis, Ruth C., Stanford, Janet L., Mucci, Lorelei A., West, Catharine M. L., Nielsen, Sune F., Kibel, Adam S., Cussenot, Olivier, Berndt, Sonja I., Koutros, Stella, Dalsgaard Sørensen, Karina, Cybulski, Cezary, Grindedal, Eli Marie, Park, Jong Y., Ingles, Sue A., Maier, Christiane, Hamilton, Robert J., Rosenstein, Barry S., Vega, Ana, The Impact Study Steering Committee And Collaborators, Kogevinas, Manolis, Wiklund, Fredrik, Penney, Kathryn L., Brenner, Hermann, John, Esther M., Kaneva, Radka, Logothetis, Christopher J., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Canary PASS Investigators, Lessel, Davor, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A., Roobol, Monique J., The Profile Study Steering Committee, The PRACTICAL Consortium, Teixeira, Manuel R., Brandão, Andreia, Paulo, Paula, Maia, Sofia, Pinheiro, Manuela, Peixoto, Ana, Cardoso, Marta, Silva, Maria P., Santos, Catarina, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth, Ukgpcs Collaborators, Schleutker, Johanna, Wang, Ying, Pashayan, Nora, Batra, Jyotsna, Apcb BioResource, Grönberg, Henrik, Neal, David E., Nordestgaard, Børge G., Tangen, Catherine M., Southey, Melissa C., Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A., Travis, Ruth C., Stanford, Janet L., Mucci, Lorelei A., West, Catharine M. L., Nielsen, Sune F., Kibel, Adam S., Cussenot, Olivier, Berndt, Sonja I., Koutros, Stella, Dalsgaard Sørensen, Karina, Cybulski, Cezary, Grindedal, Eli Marie, Park, Jong Y., Ingles, Sue A., Maier, Christiane, Hamilton, Robert J., Rosenstein, Barry S., Vega, Ana, The Impact Study Steering Committee And Collaborators, Kogevinas, Manolis, Wiklund, Fredrik, Penney, Kathryn L., Brenner, Hermann, John, Esther M., Kaneva, Radka, Logothetis, Christopher J., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Canary PASS Investigators, Lessel, Davor, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A., Roobol, Monique J., The Profile Study Steering Committee, The PRACTICAL Consortium, and Teixeira, Manuel R.

Abstract

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

Published
2020
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130. Author Correction: Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

Author

Sud, Amit, Thomsen, Hauke, Law, Philip J., Försti, Asta, da Silva Filho, Miguel Inacio, Holroyd, Amy, Broderick, Peter, Orlando, Giulia, Lenive, Oleg, Wright, Lauren, Cooke, Rosie, Easton, Douglas, Pharoah, Paul, Dunning, Alison, Peto, Julian, Canzian, Federico, Eeles, Rosalind, Kote-Jarai, Zsofia, Muir, Kenneth, Pashayan, Nora, Henderson, Brian E., Haiman, Christopher A., Benlloch, Sara, Schumacher, Fredrick R., Olama, Ali Amin Al, Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Stevens, Victoria L., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Géraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, Maehle, Lovise, Neal, David E., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Gago-Dominguez, Manuela, Roobol, Monique J., Menegaux, Florence, Hoffmann, Per, Nöthen, Markus M., Jöckel, Karl-Heinz, von Strandmann, Elke Pogge, Lightfoot, Tracy, Kane, Eleanor, Roman, Eve, Lake, Annette, Montgomery, Dorothy, Jarrett, Ruth F., Swerdlow, Anthony J., Engert, Andreas, Orr, Nick, Hemminki, Kari, and Houlston, Richard S.

Subjects
Science, Medizin, MEDLINE, General Physics and Astronomy, Genome-wide association study, Computational biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, Disease susceptibility, immune system diseases, hemic and lymphatic diseases, Classical Hodgkin lymphoma, Humans, Genetic Predisposition to Disease, Author Correction, lcsh:Science, Alleles, HLA-DP beta-Chains, Multidisciplinary, Published Erratum, General Chemistry, Hodgkin Disease, Spelling, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Key (cryptography), lcsh:Q, Psychology, Genome-Wide Association Study, HLA-DRB1 Chains
Abstract

Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10−8) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 × 10−17), 6q23.3 (rs6928977, P = 4.62 × 10−11), 10p14 (rs3781093, P = 9.49 × 10−13), 13q34 (rs112998813, P = 4.58 × 10−8) and 16p13.13 (rs34972832, P = 2.12 × 10−8). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response., Classical Hodgkin lymphoma is a cancer that originates in lymph nodes. Little is known about its genetic susceptibility. Here, the authors combined existing and new genome-wide association studies to identify risk loci for classical Hodgkin lymphoma at 6q22.33, and nodular sclerosis Hodgkin lymphoma at 3q28, 6q23.3, 10p14, 13q34, 16p13.13.

Published
2019
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131. Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature Communications, (2019), 10, 1, (431), 10.1038/s41467-018-08054-4)

Author

Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeböller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnström, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldés, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Géraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, André L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B.M., Claessens, Frank, Clements, Judith, Collée, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., deFazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Dörk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R.Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renée T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, García-Sáenz, José A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guénel, Pascal, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Høgdall, Estrid, Hong, Yun Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kühl, Tabea, Khaw, Kay Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubiński, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Marchand, Loic Le, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Børge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olama, Ali Amin Al, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Håkan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H.M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjørge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elías, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M.L., White, Emily, Whittemore, Alice S., Wichmann, H. Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, McKay, James, Peters, Ulrike, Hsu, Li, García-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D.P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, and Lindström, Sara

Subjects
head and neck, Settore MED/31 - OTORINOLARINGOIATRIA
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019
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132. Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Author

Law, Philip J., Timofeeva, Maria, Fernandez-Rozadilla, Ceres, Timofeeva, Aria, Broderick, Peter, Studd, James, Fernandez-Tajes, Juan, Farrington, Susan, Svinti, Victoria, Palles, Claire, Orlando, Giulia, Sud, Amit, Holroyd, Amy, Penegar, Steven, Theodoratou, Evropi, Vaughan-Shaw, Peter, Campbell, Harry, Zgaga, Lina, Hayward, Caroline, Campbell, Archie, Harris, Sarah, Deary, Ian J., Starr, Ohn, Gatcombe, Laura, Pinna, Maria, Briggs, Sarah, Martin, Lynn, Jaeger, Emma, Sharma-Oates, Archana, East, James, Leedham, Simon, Arnold, Roland, Johnstone, Elaine, Wang, Haitao, Kerr, David, Kerr, Rachel, Maughan, Tim, Kaplan, Richard, Al-Tassan, Nada, Palin, Kimmo, Hanninen, Ulrika A., Cajuso, Tatiana, Tanskanen, Tomas, Kondelin, Johanna, Kaasinen, Eevi, Sarin, Antti-Pekka, Eriksson, Johan G., Rissanen, Harri, Knekt, Paul, Pukkala, Eero, Jousilahti, Pekka, Salomaa, Veikko, Ripatti, Samuli, Palotie, Aarno, Renkonen-Sinisalo, Laura, Lepisto, Anna, Bohm, Jan, Mecklin, Jukka-Pekka, Buchanan, Daniel D., Win, Aung-Ko, Hopper, John, Jenkins, Mark E., Lindor, Noralane M., Newcomb, Polly A., Gallinger, Steven, Duggan, David, Casey, Graham, Hoffmann, Per, Nothen, Markus M., Jockel, Karl-Heinz, Easton, Douglas F., Pharoah, Paul D. P., Peto, Julian, Canzian, Federico, Swerdlow, Anthony, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth, Pashayan, Nora, Harkin, Andrea, Allan, Karen, McQueen, John, Paul, James, Iveson, Timothy, Saunders, Mark, Butterbach, Katja, Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Kirac, Iva, Matosevic, Petar, Hofer, Philipp, Brezina, Stefanie, Gsur, Andrea, Cheadle, Jeremy P., Aaltonen, Lauri A., Tomlinson, Ian, Houlston, Richard S., Dunlop, Malcolm G., Henderson, Brian E., Haiman, Christopher A., Schumacher, Fredrick R., Al Olama, Ali Amin, Benlloch, Sara, Berndt, Sonja, I, Conti, David, V, Wiklund, Fredrik, Chanock, Stephen, Gapstur, Susan, Stevens, Victoria L., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Schleutker, Johanna, Albanes, Demetrius, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Geraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, Grindeda, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Borge G., Maier, Christiane, Kim, Jeri, John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Gamulin, Marija, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Gago-Dominguez, Manuela, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, and Thibodeau, Stephen N.

Subjects
CHROMATIN, Cancer och onkologi, Science & Technology, IDENTIFICATION, HERITABILITY, digestive system diseases, Multidisciplinary Sciences, Cancer and Oncology, COHORT PROFILE, IMPUTATION, Science & Technology - Other Topics, TRANSCRIPTION FACTOR-BINDING, GWAS, GENOME-WIDE ASSOCIATION, neoplasms, Medical Genetics, METAANALYSIS, Medicinsk genetik
Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention. ispartof: NATURE COMMUNICATIONS vol:10 issue:1 ispartof: location:England status: published

Published
2019

136. The Implications of Genetic Testing on Radiation Therapy Decisions: A Guide for Radiation Oncologists

Author

Bergom, Carmen, primary, West, Catharine M., additional, Higginson, Daniel S., additional, Abazeed, Mohamed E., additional, Arun, Banu, additional, Bentzen, Soren M., additional, Bernstein, Jonine L., additional, Evans, Jaden D., additional, Gerber, Naamit K., additional, Kerns, Sarah L., additional, Keen, Judy, additional, Litton, Jennifer K., additional, Reiner, Anne S., additional, Riaz, Nadeem, additional, Rosenstein, Barry S., additional, Sawakuchi, Gabriel O., additional, Shaitelman, Simona F., additional, Powell, Simon N., additional, and Woodward, Wendy A., additional

Published
2019
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137. REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer

Author

Seibold, Petra, primary, Webb, Adam, additional, Aguado-Barrera, Miguel E., additional, Azria, David, additional, Bourgier, Celine, additional, Brengues, Muriel, additional, Briers, Erik, additional, Bultijnck, Renée, additional, Calvo-Crespo, Patricia, additional, Carballo, Ana, additional, Choudhury, Ananya, additional, Cicchetti, Alessandro, additional, Claßen, Johannes, additional, Delmastro, Elena, additional, Dunning, Alison M., additional, Elliott, Rebecca M., additional, Fachal, Laura, additional, Farcy-Jacquet, Marie-Pierre, additional, Gabriele, Pietro, additional, Garibaldi, Elisabetta, additional, Gómez-Caamaño, Antonio, additional, Gutiérrez-Enríquez, Sara, additional, Higginson, Daniel S., additional, Johnson, Kerstie, additional, Lobato-Busto, Ramón, additional, Mollà, Meritxell, additional, Müller, Anusha, additional, Payne, Debbie, additional, Peleteiro, Paula, additional, Post, Giselle, additional, Rancati, Tiziana, additional, Rattay, Tim, additional, Reyes, Victoria, additional, Rosenstein, Barry S., additional, De Ruysscher, Dirk, additional, De Santis, Maria Carmen, additional, Schäfer, Jörg, additional, Schnabel, Thomas, additional, Sperk, Elena, additional, Symonds, R. Paul, additional, Stobart, Hilary, additional, Taboada-Valladares, Begoña, additional, Talbot, Christopher J., additional, Valdagni, Riccardo, additional, Vega, Ana, additional, Veldeman, Liv, additional, Ward, Tim, additional, Weißenberger, Christian, additional, West, Catharine M.L., additional, Chang-Claude, Jenny, additional, Lievens, Yolande, additional, van Eijkeren, Marc, additional, Vandecasteele, Katrien, additional, Elhamin, Elhaseen, additional, Ost, Piet, additional, Fonteyne, Valérie, additional, Swimberghe, Martijn, additional, Deseyne, Pieter, additional, De Neve, Wilfried, additional, Duprez, Fréderic, additional, Mareel, Marcus, additional, Monten, Chris, additional, Van Greveling, Annick, additional, Vercauteren, Tom, additional, Paelinck, Leen, additional, Defraene, Gilles, additional, Aerts, Rita, additional, Arredouani, Soumia, additional, Lambrecht, Maarten, additional, Vanneste, Ben, additional, Draghici, Roxana, additional, Giordano, Frank, additional, Herskind, Carsten, additional, Veldwijk, Marlon, additional, Helmbold, Irmgard, additional, Giesche, Ulrich, additional, Stegmaier, Petra, additional, Weiß, Christian, additional, Blaschke, Thomas, additional, Neu, Burkhard, additional, Lozza, Laura, additional, Avuzzi, Barbara, additional, Morlino, Sara, additional, Sangalli, Claudia, additional, Franceschini, Marzia, additional, Rodriguez-Lage, Belina, additional, Fernández-Tajes, Juan, additional, Fuentes-Rios, Olivia, additional, Domínguez-Rios, Isabel, additional, Fajardo-Paneque, Irene, additional, Sosa-Fajardo, Paloma, additional, Torrado-Moya, Laura, additional, Ramos-Albiac, Mónica, additional, Giraldo, Alexandra, additional, Altabas, Manolo, additional, Piqué-Leiva, Bibiana, additional, García-Relancio, David, additional, Seoane-Ramallo, Alejandro, additional, Lavers, Samuel, additional, Wright, Simon, additional, Dobbelaere, Hannah, additional, Appleton, Donna, additional, Kaushik, Monika, additional, Kenny, Frances, additional, Khout, Hazem, additional, Krupa, Jaroslaw, additional, Lambert, Kelly V., additional, Pilgrim, Simon, additional, Shokuhi, Sheila, additional, Valassiadou, Kalliope, additional, Aznar-Garcia, Luis, additional, Boiangui, Ion, additional, Kancherla, Kiran, additional, Kent, Christopher, additional, Sampson, Kufre, additional, Osman, Ahmed, additional, Sridhar, Thiagarajan, additional, Vasanthan, Subramaniam, additional, Faivre-Finn, Corinne, additional, Harrop, Victoria, additional, Keni, Manjusha, additional, Foweraker, Karen, additional, Pascoe, Abigail, additional, Esler, Claire, additional, Stock, Richard, additional, Green, Sheryl, additional, Golchin, Ava, additional, and Li, William, additional

Published
2019
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138. Radiogenomics Consortium Genome-Wide Association Study Meta-Analysis of Late Toxicity After Prostate Cancer Radiotherapy

Author

Kerns, Sarah L, primary, Fachal, Laura, additional, Dorling, Leila, additional, Barnett, Gillian C, additional, Baran, Andrea, additional, Peterson, Derick R, additional, Hollenberg, Michelle, additional, Hao, Ke, additional, Narzo, Antonio Di, additional, Ahsen, Mehmet Eren, additional, Pandey, Gaurav, additional, Bentzen, Søren M, additional, Janelsins, Michelle, additional, Elliott, Rebecca M, additional, Pharoah, Paul D P, additional, Burnet, Neil G, additional, Dearnaley, David P, additional, Gulliford, Sarah L, additional, Hall, Emma, additional, Sydes, Matthew R, additional, Aguado-Barrera, Miguel E, additional, Gómez-Caamaño, Antonio, additional, Carballo, Ana M, additional, Peleteiro, Paula, additional, Lobato-Busto, Ramón, additional, Stock, Richard, additional, Stone, Nelson N, additional, Ostrer, Harry, additional, Usmani, Nawaid, additional, Singhal, Sandeep, additional, Tsuji, Hiroshi, additional, Imai, Takashi, additional, Saito, Shiro, additional, Eeles, Rosalind, additional, DeRuyck, Kim, additional, Parliament, Matthew, additional, Dunning, Alison M, additional, Vega, Ana, additional, Rosenstein, Barry S, additional, and West, Catharine M L, additional

Published
2019
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140. Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study

Author

Adams, Charleen, Richmond, Rebecca C., Santos Ferreira, Diana L, Spiller, Wes, Tan, Vanessa Y, Zheng, Jie, Wurtz, Peter, Donovan, Jenny L, Hamdy, Freddie C, Neal, David E, Lane, J Athene, Davey Smith, George, Relton, Caroline L, Eeles, Rosalind A, Henderson, Brian E, Haiman, Christopher A, Kote-Jarai, Zsofia, Schumacher, Fredrick R, Amin Al Olama, Ali, Benlloch, Sara, Muir, Kenneth, Berndt, Sonja I, Conti, David V, Wiklund, Fredrik, Chanock, Stephen J, Gapstur, Susan M, Stevens, Victoria L, Tangen, Catherine M, Batra, Jyotsna, Clements, Judith A, Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Wolk, Alicja, West, Catharine M L, Mucci, Lorelei A, Cancel-Tassin, Geraldine, Koutros, Stella, Sørensen, Karina D, Maehle, Lovise, Travis, Ruth C, Hamilton, Robert, Ingles, Sue Ann, Rosenstein, Barry S, Lu, Yong-Jie, Giles, Graham G, Kibel, Adam S, Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L, Park, Jong Y, Stanford, Janet L, Cybulski, Cezary, Nordestgaard, Borge G, Brenner, Hermann, Maier, Christiane, Kim, Jeri, John, Esther M, Teixeira, Manuel R, Neuhausen, Susan L, DeRuyck, Kim, Razack, Azad, Newcomb, Lisa F, Lessel, Davor, Kaneva, Radka P, Usmani, Nawaid, Claessens, Frank, Townsend, Paul, Gago Dominguez, Manuela, Roobol, Monique J, Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A, Pandha, Hardev, Thibodeau, Stephen N, Martin, Richard M, Adams, Charleen, Richmond, Rebecca C., Santos Ferreira, Diana L, Spiller, Wes, Tan, Vanessa Y, Zheng, Jie, Wurtz, Peter, Donovan, Jenny L, Hamdy, Freddie C, Neal, David E, Lane, J Athene, Davey Smith, George, Relton, Caroline L, Eeles, Rosalind A, Henderson, Brian E, Haiman, Christopher A, Kote-Jarai, Zsofia, Schumacher, Fredrick R, Amin Al Olama, Ali, Benlloch, Sara, Muir, Kenneth, Berndt, Sonja I, Conti, David V, Wiklund, Fredrik, Chanock, Stephen J, Gapstur, Susan M, Stevens, Victoria L, Tangen, Catherine M, Batra, Jyotsna, Clements, Judith A, Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Wolk, Alicja, West, Catharine M L, Mucci, Lorelei A, Cancel-Tassin, Geraldine, Koutros, Stella, Sørensen, Karina D, Maehle, Lovise, Travis, Ruth C, Hamilton, Robert, Ingles, Sue Ann, Rosenstein, Barry S, Lu, Yong-Jie, Giles, Graham G, Kibel, Adam S, Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L, Park, Jong Y, Stanford, Janet L, Cybulski, Cezary, Nordestgaard, Borge G, Brenner, Hermann, Maier, Christiane, Kim, Jeri, John, Esther M, Teixeira, Manuel R, Neuhausen, Susan L, DeRuyck, Kim, Razack, Azad, Newcomb, Lisa F, Lessel, Davor, Kaneva, Radka P, Usmani, Nawaid, Claessens, Frank, Townsend, Paul, Gago Dominguez, Manuela, Roobol, Monique J, Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A, Pandha, Hardev, Thibodeau, Stephen N, and Martin, Richard M

Abstract

BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR). MATERIALS AND METHODS: The case-control portion of the study was conducted in nine UK centres with men aged 50-69 years who underwent prostate-specific antigen (PSA) screening for prostate cancer within the Prostate testing for cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (p <0.0014, multiple-testing threshold). These fell into four classes: i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); ii) fatty acids and ratios; iii) amino acids; iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

Published
2019
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141. Author Correction : Germline variation at 8q24 and prostate cancer risk in men of European ancestry.

Author

Matejcic, Marco, Saunders, Edward J, Dadaev, Tokhir, Brook, Mark N, Wang, Kan, Sheng, Xin, Olama, Ali Amin Al, Schumacher, Fredrick R, Ingles, Sue A, Govindasami, Koveela, Benlloch, Sara, Berndt, Sonja I, Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L, Gapstur, Susan M, Tangen, Catherine M, Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Kraft, Peter, Cancel-Tassin, Géraldine, Sorensen, Karina D, Maehle, Lovise, Grindedal, Eli M, Strom, Sara S, Neal, David E, Hamdy, Freddie C, Donovan, Jenny L, Travis, Ruth C, Hamilton, Robert J, Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G, Kibel, Adam S, Vega, Ana, Bensen, Jeanette T, Kogevinas, Manolis, Penney, Kathryn L, Park, Jong Y, Stanford, Janet L, Cybulski, Cezary, Nordestgaard, Børge G, Brenner, Hermann, Maier, Christiane, Kim, Jeri, Teixeira, Manuel R, Neuhausen, Susan L, De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F, Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A, Gago-Dominguez, Manuela, Roobol, Monique J, Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A, Pandha, Hardev, Thibodeau, Stephen N, Schaid, Daniel J, Wiklund, Fredrik, Chanock, Stephen J, Easton, Douglas F, Eeles, Rosalind A, Kote-Jarai, Zsofia, Conti, David V, Haiman, Christopher A, Matejcic, Marco, Saunders, Edward J, Dadaev, Tokhir, Brook, Mark N, Wang, Kan, Sheng, Xin, Olama, Ali Amin Al, Schumacher, Fredrick R, Ingles, Sue A, Govindasami, Koveela, Benlloch, Sara, Berndt, Sonja I, Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L, Gapstur, Susan M, Tangen, Catherine M, Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Kraft, Peter, Cancel-Tassin, Géraldine, Sorensen, Karina D, Maehle, Lovise, Grindedal, Eli M, Strom, Sara S, Neal, David E, Hamdy, Freddie C, Donovan, Jenny L, Travis, Ruth C, Hamilton, Robert J, Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G, Kibel, Adam S, Vega, Ana, Bensen, Jeanette T, Kogevinas, Manolis, Penney, Kathryn L, Park, Jong Y, Stanford, Janet L, Cybulski, Cezary, Nordestgaard, Børge G, Brenner, Hermann, Maier, Christiane, Kim, Jeri, Teixeira, Manuel R, Neuhausen, Susan L, De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F, Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A, Gago-Dominguez, Manuela, Roobol, Monique J, Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A, Pandha, Hardev, Thibodeau, Stephen N, Schaid, Daniel J, Wiklund, Fredrik, Chanock, Stephen J, Easton, Douglas F, Eeles, Rosalind A, Kote-Jarai, Zsofia, Conti, David V, and Haiman, Christopher A

Abstract

The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

Published
2019
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142. Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score

Author

Huynh-Le, Minh-Phuong, Karunamuni, Roshan, Fan, Chun Chieh, Asona, Lui, Thompson, Wesley K., Martinez, Maria Elena, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth R., Lophatananon, Artitaya, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, Grönberg, Henrik, Neal, David E., Nordestgaard, Børge G., Tangen, Catherine M., MacInnis, Robert J., Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A., Travis, Ruth C., Blot, William J., Stanford, Janet L., Mucci, Lorelei A., West, Catharine M. L., Nielsen, Sune F., Kibel, Adam S., Cussenot, Olivier, Berndt, Sonja I., Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Menegaux, Florence, Park, Jong Y., Ingles, Sue A., Maier, Christiane, Hamilton, Robert J., Rosenstein, Barry S., Lu, Yong-Jie, Watya, Stephen, Vega, Ana, Kogevinas, Manolis, Wiklund, Fredrik, Penney, Kathryn L., Huff, Chad D., Teixeira, Manuel R., Multigner, Luc, Leach, Robin J., Brenner, Hermann, John, Esther M., Kaneva, Radka, Logothetis, Christopher J., Neuhausen, Susan L., De Ruyck, Kim, Ost, Piet, Razack, Azad, Newcomb, Lisa F., Fowke, Jay H., Gamulin, Marija, Abraham, Aswin, Claessens, Frank, Castelao, Jose Esteban, Townsend, Paul A., Crawford, Dana C., Petrovics, Gyorgy, van Schaik, Ron H. N., Parent, Marie-Élise, Hu, Jennifer J., Zheng, Wei, Mills, Ian G., Andreassen, Ole A., Dale, Anders M., and Seibert, Tyler M.

Abstract

Background: Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets. Methods: In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry—the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured. Results: The final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43–15.16] in ProtecT, 7.07 [6.58–7.60] in African ancestry, 10.31 [9.58–11.11] in Asian ancestry, and 11.18 [10.34–12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11–0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15–0.22) and 0.26 (0.19–0.33), respectively. Conclusions: We demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.

Published
2022
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146. Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Author

Went, Molly, Sud, Amit, Försti, Asta, Halvarsson, Britt-Marie, Weinhold, Niels, Kimber, Scott, van Duin, Mark, Thorleifsson, Gudmar, Holroyd, Amy, Johnson, David C., Li, Ni, Orlando, Giulia, Law, Philip J., Ali, Mina, Chen, Bowang, Mitchell, Jonathan S., Gudbjartsson, Daniel F., Kuiper, Rowan, Stephens, Owen W., Bertsch, Uta, Broderick, Peter, Campo, Chiara, Bandapalli, Obul R, Einsele, Hermann, Gregory, Walter A., Gullberg, Urban, Hillengass, Jens, Hoffmann, Per, Jackson, Graham H., Jöckel, Karl-Heinz, Johnsson, Ellinor, Kristinsson, Sigurður Y., Mellqvist, Ulf-Henrik, Nahi, Hareth, Easton, Douglas, Pharoah, Paul, Dunning, Alison, Peto, Julian, Canzian, Federico, Swerdlow, Anthony, Eeles, Rosalind A., Kote-Jarai, ZSofia, Muir, Kenneth, Pashayan, Nora, Nickel, Jolanta, Nöthen, Markus M., Rafnar, Thorunn, Ross, Fiona M., da Silva Filho, Miguel Inacio, Thomsen, Hauke, Turesson, Ingemar, Vangsted, Annette, Andersen, Niels Frost, Waage, Anders, Walker, Brian A., Wihlborg, Anna-Karin, Broyl, Annemiek, Davies, Faith E., Thorsteinsdottir, Unnur, Langer, Christian, Hansson, Markus, Goldschmidt, Hartmut, Kaiser, Martin, Sonneveld, Pieter, Stefansson, Kari, Morgan, Gareth J., Hemminki, Kari, Nilsson, Björn, Houlston, Richard S., Henderson, Brian E., Haiman, Christopher A., Benlloch, Sara, Schumacher, Fredrick R., Olama, Ali Amin Al, Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Stevens, Victoria L., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Géraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Dominguez, Manuela Gago, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, and Thibodeau, Stephen N.

Subjects
Medizin
Abstract

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM. CA extern

Published
2018

147. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Author

Dadaev, Tokhir, Saunders, Edward J., Newcombe, Paul J., Anokian, Ezequiel, Leongamornlert, Daniel A., Brook, Mark N., Cieza-Borrella, Clara, Mijuskovic, Martina, Wakerell, Sarah, Olama, Ali Amin Al, Schumacher, Fredrick R., Berndt, Sonja I., Benlloch, Sara, Ahmed, Mahbubl, Goh, Chee, Sheng, Xin, Zhang, Zhuo, Muir, Kenneth, Govindasami, Koveela, Lophatananon, Artitaya, Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Tangen, Catherine M., Goodman, Phyllis, Thompson, Ian M., Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail, 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, Hakansson, Niclas, West, Catharine, Dunning, Alison M., Burnet, Neil, Mucci, Lorelei, Giovannucci, Edward, Andriole, Gerald, Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Freeman, Laura E.Beane, 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, Kerns, Sarah, 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, Fachal, Laura, 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., Weisher, 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, Slavov, Chavdar, Mitev, Vanio, Parliament, Matthew, Singhal, Sandeep, 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, Kierzek, Andrzej, 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., Kraft, Peter, Cook, Margaret, Thwaites, Alison, Guy, Michelle, Whitmore, Ian, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Spurdle, Amanda, Srinivasan, Srilakshmi, Kedda, Mary Anne, Aitken, Joanne, Gardiner, Robert, Hayes, Vanessa, Butler, Lisa, Taylor, Renea, Yeadon, Trina, Eckert, Allison, Saunders, Pamela, Haynes, Anne Maree, Papargiris, Melissa, Kujala, Paula, Talala, Kirsi, Murtola, Teemu, Taari, Kimmo, Dearnaley, David, Barnett, Gill, Bentzen, Søren, Elliott, Rebecca, Ranu, Hardeep, Hicks, Belynda, Vogt, Aurelie, Hutchinson, Amy, Cox, Angela, Davis, Michael, Brown, Paul, George, Anne, Marsden, Gemma, Lane, Athene, Lewis, Sarah J., Berry, Clare, Kulkarni, Girish S., Toi, Ants, Evans, Andrew, Zlotta, Alexandre R., Van Der Kwast, Theodorus H., Imai, Takashi, Saito, Shiro, Marzec, Jacek, Cao, Guangwen, Lin, Ji, Ling, Jin, Li, Meiling, Zhao, Shan Chao, Ren, Guoping, Yu, Yongwei, Wu, Yudong, Wu, Ji, Zhou, Bo, Zhang, Yangling, Li, Jie, He, Weiyang, Guo, Jianming, Pedersen, John, Hopper, John L., Milne, Roger, Klim, Aleksandra, Carballo, Ana, Lobato-Busto, Ramón, Peleteiro, Paula, Calvo, Patricia, Aguado, Miguel, Ruiz-Dominguez, José Manuel, Cecchini, Lluís, Mengual, Lourdes, Alcaraz, Antonio, Bustamante, Mariona, Gracia-Lavedan, Esther, Dierssen-Sotos, Trinidad, Gomez-Acebo, Ines, Pow-Sang, Julio, Park, Hyun, Zachariah, Babu, Kluzniak, Wojciech, Kolb, Suzanne, Klarskov, Peter, Stegmaier, Christa, Vogel, Walther, Herkommer, Kathleen, Bohnert, Philipp, Maia, Sofia, Silva, Maria P., De Langhe, Sofie, Thierens, Hubert, Tan, Meng H., Ong, Aik T., Kastelan, Zeljko, Popov, Elenko, Kachakova, Darina, Mitkova, Atanaska, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Carracedo, Angel, Bangma, Christopher, Schroder, F. H., Cenee, Sylvie, Tretarre, Brigitte, Rebillard, Xavier, Mulot, Claire, Sanchez, Marie, Adolfsson, Jan, Stattin, Par, Johansson, Jan Erik, Cavalli-Bjoerkman, Carin, Karlsson, Ami, Broms, Michael, Wu, Huihai, Tillmans, Lori, Riska, Shaun, Freedman, Matthew, Wiklund, Fredrik, Chanock, Stephen, Henderson, Brian E., Easton, Douglas F., Haiman, Christopher A., Eeles, Rosalind A., Conti, David V., and Kote-Jarai, Zsofia

Abstract

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.

Published
2018
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148. Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia

Author

Vijayakrishnan, Jayaram, Studd, James, Broderick, Peter, Kinnersley, Ben, Holroyd, Amy, Law, Philip J., Kumar, Rajiv, Allan, James M., Harrison, Christine J., Moorman, Anthony V., Vora, Ajay, Roman, Eve, Rachakonda, Sivaramakrishna, Kinsey, Sally E., Sheridan, Eamonn, Thompson, Pamela D., Irving, Julie A., Koehler, Rolf, Hoffmann, Per, Nöthen, Markus M., Heilmann-Heimbach, Stefanie, Jöckel, Karl-Heinz, Easton, Douglas F., Pharaoh, Paul D.P., Dunning, Alison M., Peto, Julian, Canzian, Frederico, Swerdlow, Anthony, Eeles, Rosalind A., Kote-Jarai, ZSofia, Muir, Kenneth, Pashayan, Nora, Greaves, Mel, Zimmerman, Martin, Bartram, Claus R., Schrappe, Martin, Stanulla, Martin, Hemminki, Kari, Houlston, Richard S., Henderson, Brian E., Haiman, Christopher A., Benlloch, Sara, Schumacher, Fredrick R., Olama, Ali Amin Al, Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Stevens, Victoria L., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Géraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, Maehle, Lovise, Neal, David E., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Dominguez, Manuela Gago, Roobol, Monique J., Menegaux, Florence, and Urology

Subjects
Medizin
Abstract

Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10⁻⁹, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10⁻⁸, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology. OA gold - CA extern

Published
2018

149. Large-scale transcriptome-wide association study identifies new prostate cancer risk regions

Author

Mancuso, Nicholas, Gayther, Simon, Gusev, Alexander, Zheng, Wei, Penney, Kathryn L., Kote-Jarai, Zsofia, Eeles, Rosalind, Freedman, Matthew, Haiman, Christopher, Pasaniuc, Bogdan, Henderson, Brian E., Benlloch, Sara, Schumacher, Fredrick R., Olama, Ali Amin Al, Muir, Kenneth, Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Stevens, Victoria L., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Géraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, Maehle, Lovise, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry, Lu, Yong Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Park, Jong Y., Stanford, Janet L., Nordestgaard, Børge G., and Urology

Subjects
0301 basic medicine, Male, General Physics and Astronomy, Genome-wide association study, VARIANTS, urologic and male genital diseases, medicine.disease_cause, DISEASE, Transcriptome, Prostate cancer, 0302 clinical medicine, lcsh:Science, GENE-EXPRESSION, Prostate cancer risk, 0303 health sciences, Multidisciplinary, Manchester Cancer Research Centre, HERITABILITY, Prostatic Neoplasms/genetics, CARDIOVASCULAR RISK, 3. Good health, Multidisciplinary Sciences, CAUSAL GENES, 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Medical Genetics, SUSCEPTIBILITY LOCI, Scale (ratio), Science, Urology, MEDLINE, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, SNP, Humans, Genetic Predisposition to Disease, FINNISH MEN, Gene, Medicinsk genetik, 030304 developmental biology, Genetic association, Science & Technology, business.industry, COMPLEX TRAITS, ResearchInstitutes_Networks_Beacons/mcrc, Alternative splicing, Cancer, Prostatic Neoplasms, General Chemistry, medicine.disease, 030104 developmental biology, YOUNG FINNS, Human genome, lcsh:Q, business, Carcinogenesis, Genome-Wide Association Study
Abstract

Although genome-wide association studies (GWAS) for prostate cancer (PrCa) have identified more than 100 risk regions, most of the risk genes at these regions remain largely unknown. Here we integrate the largest PrCa GWAS (N = 142,392) with gene expression measured in 45 tissues (N = 4458), including normal and tumor prostate, to perform a multi-tissue transcriptome-wide association study (TWAS) for PrCa. We identify 217 genes at 84 independent 1 Mb regions associated with PrCa risk, 9 of which are regions with no genome-wide significant SNP within 2 Mb. 23 genes are significant in TWAS only for alternative splicing models in prostate tumor thus supporting the hypothesis of splicing driving risk for continued oncogenesis. Finally, we use a Bayesian probabilistic approach to estimate credible sets of genes containing the causal gene at a pre-defined level; this reduced the list of 217 associations to 109 genes in the 90% credible set. Overall, our findings highlight the power of integrating expression with PrCa GWAS to identify novel risk loci and prioritize putative causal genes at known risk loci., Genome-wide association studies (GWAS) have identified hundreds of genomic risk regions for prostate cancer. Here, the authors perform a transcriptome wide association study (TWAS) by incorporating prostate cancer GWAS with gene expression data to identify potential novel prostate cancer risk loci and possible risk mechanisms.

Published
2018
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