Conti, D.V.
Darst, B.F.
Moss, L.C.
Saunders, E.J.
Sheng, X.
Chou, A.
Schumacher, F.R.
Olama, A.A.
Benlloch, S.
Dadaev, T.
Brook, M.N.
Sahimi, A.
Hoffmann, T.J.
Takahashi, A.
Matsuda, K.
Momozawa, Y.
Fujita, M.
Muir, K.
Lophatananon, A.
Wan, P.
Le Marchand, L.
Wilkens, L.R.
Stevens, V.L.
Gapstur, S.M.
Carter, B.D.
Schleutker, J.
Tammela, T.L.
Sipeky, C.
Auvinen, A.
Giles, G.G.
Southey, M.C.
MacInnis, R.J.
Cybulski, C.
Wokołorczyk, D.
Lubiński, J.
Neal, D.E.
Donovan, J.L.
Hamdy, F.C.
Martin, R.M.
Nordestgaard, B.G.
Nielsen, S.F.
Weischer, M.
Bojesen, S.E.
Røder, M.A.
Iversen, P.
Batra, J.
Chambers, S.
Moya, L.
Horvath, L.
Clements, J.A.
Tilley, W.
Risbridger, G.P.
Gronberg, H.
Aly, M.
Szulkin, R.
Eklund, M.
Nordström, T.
Pashayan, N.
Dunning, A.M.
Ghoussaini, M.
Travis, R.C.
Key, T.J.
Riboli, E.
Park, J.Y.
Sellers, T.A.
Lin, H.-.
Albanes, D.
Weinstein, S.J.
Mucci, L.A.
Giovannucci, E.
Lindstrom, S.
Kraft, P.
Hunter, D.J.
Penney, K.L.
Turman, C.
Tangen, C.M.
Goodman, P.J.
Thompson, I.M.
Hamilton, R.J.
Fleshner, N.E.
Finelli, A.
Parent, M.-.
Stanford, J.L.
Ostrander, E.A.
Geybels, M.S.
Koutros, S.
Freeman, L.E.
Stampfer, M.
Wolk, A.
Håkansson, N.
Andriole, G.L.
Hoover, R.N.
Machiela, M.J.
Sørensen, K.D.
Borre, M.
Blot, W.J.
Zheng, W.
Yeboah, E.D.
Mensah, J.E.
Lu, Y.-.
Zhang, H.-.
Feng, N.
Mao, X.
Wu, Y.
Zhao, S.-.
Sun, Z.
Thibodeau, S.N.
McDonnell, S.K.
Schaid, D.J.
West, C.M.
Burnet, N.
Barnett, G.
Maier, C.
Schnoeller, T.
Luedeke, M.
Kibel, A.S.
Drake, B.F.
Cussenot, O.
Cancel-Tassin, G.
Menegaux, F.
Truong, T.
Koudou, Y.A.
John, E.M.
Grindedal, E.M.
Maehle, L.
Khaw, K.-.
Ingles, S.A.
Stern, M.C.
Vega, A.
Gómez-Caamaño, A.
Fachal, L.
Rosenstein, B.S.
Kerns, S.L.
Ostrer, H.
Teixeira, M.R.
Paulo, P.
Brandão, A.
Watya, S.
Lubwama, A.
Bensen, J.T.
Fontham, E.T.
Mohler, J.
Taylor, J.A.
Kogevinas, M.
Llorca, J.
Castaño-Vinyals, G.
Cannon-Albright, L.
Teerlink, C.C.
Huff, C.D.
Strom, S.S.
Multigner, L.
Blanchet, P.
Brureau, L.
Kaneva, R.
Slavov, C.
Mitev, V.
Leach, R.J.
Weaver, B.
Brenner, H.
Cuk, K.
Holleczek, B.
Saum, K.-.
Klein, E.A.
Hsing, A.W.
Kittles, R.A.
Murphy, A.B.
Logothetis, C.J.
Kim, J.
Neuhausen, S.L.
Steele, L.
Ding, Y.C.
Isaacs, W.B.
Nemesure, B.
Hennis, A.J.
Carpten, J.
Pandha, H.
Michael, A.
De Ruyck, K.
De Meerleer, G.
Ost, P.
Xu, J.
Razack, A.
Lim, J.
Teo, S.-.
Newcomb, L.F.
Lin, D.W.
Fowke, J.H.
Neslund-Dudas, C.
Rybicki, B.A.
Gamulin, M.
Lessel, D.
Kulis, T.
Usmani, N.
Singhal, S.
Parliament, M.
Claessens, F.
Joniau, S.
Van den Broeck, T.
Gago-Dominguez, M.
Castelao, J.E.
Martinez, M.E.
Larkin, S.
Townsend, P.A.
Aukim-Hastie, C.
Bush, W.S.
Aldrich, M.C.
Crawford, D.C.
Srivastava, S.
Cullen, J.C.
Petrovics, G.
Casey, G.
Roobol, M.J.
Jenster, G.
van Schaik, R.H.
Hu, J.J.
Sanderson, M.
Varma, R.
McKean-Cowdin, R.
Torres, M.
Mancuso, N.
Berndt, S.I.
Van Den Eeden, S.K.
Easton, D.F.
Chanock, S.J.
Cook, M.B.
Wiklund, F.
Nakagawa, H.
Witte, J.S.
Eeles, R.A.
Kote-Jarai, Z.
Haiman, C.A.
(2021). Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nat genet,
Vol.53
(1),
pp. 65-75.
show abstract
full text
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..
Karlsson, Q.
Brook, M.N.
Dadaev, T.
Wakerell, S.
Saunders, E.J.
Muir, K.
Neal, D.E.
Giles, G.G.
MacInnis, R.J.
Thibodeau, S.N.
McDonnell, S.K.
Cannon-Albright, L.
Teixeira, M.R.
Paulo, P.
Cardoso, M.
Huff, C.
Li, D.
Yao, Y.
Scheet, P.
Permuth, J.B.
Stanford, J.L.
Dai, J.Y.
Ostrander, E.A.
Cussenot, O.
Cancel-Tassin, G.
Hoegel, J.
Herkommer, K.
Schleutker, J.
Tammela, T.L.
Rathinakannan, V.
Sipeky, C.
Wiklund, F.
Grönberg, H.
Aly, M.
Isaacs, W.B.
Dickinson, J.L.
FitzGerald, L.M.
Chua, M.L.
Nguyen-Dumont, T.
PRACTICAL Consortium,
Schaid, D.J.
Southey, M.C.
Eeles, R.A.
Kote-Jarai, Z.
(2021). Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study. Eur urol oncol,
Vol.4
(4),
pp. 570-579.
show abstract
full text
BACKGROUND: Germline ATM mutations are suggested to contribute to predisposition to prostate cancer (PrCa). Previous studies have had inadequate power to estimate variant effect sizes. OBJECTIVE: To precisely estimate the contribution of germline ATM mutations to PrCa risk. DESIGN, SETTING, AND PARTICIPANTS: We analysed next-generation sequencing data from 13 PRACTICAL study groups comprising 5560 cases and 3353 controls of European ancestry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Variant Call Format files were harmonised, annotated for rare ATM variants, and classified as tier 1 (likely pathogenic) or tier 2 (potentially deleterious). Associations with overall PrCa risk and clinical subtypes were estimated. RESULTS AND LIMITATIONS: PrCa risk was higher in carriers of a tier 1 germline ATM variant, with an overall odds ratio (OR) of 4.4 (95% confidence interval [CI]: 2.0-9.5). There was also evidence that PrCa cases with younger age at diagnosis (<65 yr) had elevated tier 1 variant frequencies (pdifference = 0.04). Tier 2 variants were also associated with PrCa risk, with an OR of 1.4 (95% CI: 1.1-1.7). CONCLUSIONS: Carriers of pathogenic ATM variants have an elevated risk of developing PrCa and are at an increased risk for earlier-onset disease presentation. These results provide information for counselling of men and their families. PATIENT SUMMARY: In this study, we estimated that men who inherit a likely pathogenic mutation in the ATM gene had an approximately a fourfold risk of developing prostate cancer. In addition, they are likely to develop the disease earlier..
Eeles, R.A.
Olama, A.A.
Benlloch, S.
Saunders, E.J.
Leongamornlert, D.A.
Tymrakiewicz, M.
Ghoussaini, M.
Luccarini, C.
Dennis, J.
Jugurnauth-Little, S.
Dadaev, T.
Neal, D.E.
Hamdy, F.C.
Donovan, J.L.
Muir, K.
Giles, G.G.
Severi, G.
Wiklund, F.
Gronberg, H.
Haiman, C.A.
Schumacher, F.
Henderson, B.E.
Le Marchand, L.
Lindstrom, S.
Kraft, P.
Hunter, D.J.
Gapstur, S.
Chanock, S.J.
Berndt, S.I.
Albanes, D.
Andriole, G.
Schleutker, J.
Weischer, M.
Canzian, F.
Riboli, E.
Key, T.J.
Travis, R.C.
Campa, D.
Ingles, S.A.
John, E.M.
Hayes, R.B.
Pharoah, P.D.
Pashayan, N.
Khaw, K.-.
Stanford, J.L.
Ostrander, E.A.
Signorello, L.B.
Thibodeau, S.N.
Schaid, D.
Maier, C.
Vogel, W.
Kibel, A.S.
Cybulski, C.
Lubinski, J.
Cannon-Albright, L.
Brenner, H.
Park, J.Y.
Kaneva, R.
Batra, J.
Spurdle, A.B.
Clements, J.A.
Teixeira, M.R.
Dicks, E.
Lee, A.
Dunning, A.M.
Baynes, C.
Conroy, D.
Maranian, M.J.
Ahmed, S.
Govindasami, K.
Guy, M.
Wilkinson, R.A.
Sawyer, E.J.
Morgan, A.
Dearnaley, D.P.
Horwich, A.
Huddart, R.A.
Khoo, V.S.
Parker, C.C.
Van As, N.J.
Woodhouse, C.J.
Thompson, A.
Dudderidge, T.
Ogden, C.
Cooper, C.S.
Lophatananon, A.
Cox, A.
Southey, M.C.
Hopper, J.L.
English, D.R.
Aly, M.
Adolfsson, J.
Xu, J.
Zheng, S.L.
Yeager, M.
Kaaks, R.
Diver, W.R.
Gaudet, M.M.
Stern, M.C.
Corral, R.
Joshi, A.D.
Shahabi, A.
Wahlfors, T.
Tammela, T.L.
Auvinen, A.
Virtamo, J.
Klarskov, P.
Nordestgaard, B.G.
Røder, M.A.
Nielsen, S.F.
Bojesen, S.E.
Siddiq, A.
Fitzgerald, L.M.
Kolb, S.
Kwon, E.M.
Karyadi, D.M.
Blot, W.J.
Zheng, W.
Cai, Q.
McDonnell, S.K.
Rinckleb, A.E.
Drake, B.
Colditz, G.
Wokolorczyk, D.
Stephenson, R.A.
Teerlink, C.
Muller, H.
Rothenbacher, D.
Sellers, T.A.
Lin, H.-.
Slavov, C.
Mitev, V.
Lose, F.
Srinivasan, S.
Maia, S.
Paulo, P.
Lange, E.
Cooney, K.A.
Antoniou, A.C.
Vincent, D.
Bacot, F.
Tessier, D.C.
COGS–Cancer Research UK GWAS–ELLIPSE (part of GAME-ON) Initiative,
Australian Prostate Cancer Bioresource,
UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology,
UK ProtecT (Prostate testing for cancer and Treatment) Study Collaborators,
PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium,
Kote-Jarai, Z.
Easton, D.F.
(2013). Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat genet,
Vol.45
(4),
pp. 385-391e2.
show abstract
Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies..
Kote-Jarai, Z.
Saunders, E.J.
Leongamornlert, D.A.
Tymrakiewicz, M.
Dadaev, T.
Jugurnauth-Little, S.
Ross-Adams, H.
Al Olama, A.A.
Benlloch, S.
Halim, S.
Russell, R.
Dunning, A.M.
Luccarini, C.
Dennis, J.
Neal, D.E.
Hamdy, F.C.
Donovan, J.L.
Muir, K.
Giles, G.G.
Severi, G.
Wiklund, F.
Gronberg, H.
Haiman, C.A.
Schumacher, F.
Henderson, B.E.
Le Marchand, L.
Lindstrom, S.
Kraft, P.
Hunter, D.J.
Gapstur, S.
Chanock, S.
Berndt, S.I.
Albanes, D.
Andriole, G.
Schleutker, J.
Weischer, M.
Canzian, F.
Riboli, E.
Key, T.J.
Travis, R.C.
Campa, D.
Ingles, S.A.
John, E.M.
Hayes, R.B.
Pharoah, P.
Khaw, K.-.
Stanford, J.L.
Ostrander, E.A.
Signorello, L.B.
Thibodeau, S.N.
Schaid, D.
Maier, C.
Vogel, W.
Kibel, A.S.
Cybulski, C.
Lubinski, J.
Cannon-Albright, L.
Brenner, H.
Park, J.Y.
Kaneva, R.
Batra, J.
Spurdle, A.
Clements, J.A.
Teixeira, M.R.
Govindasami, K.
Guy, M.
Wilkinson, R.A.
Sawyer, E.J.
Morgan, A.
Dicks, E.
Baynes, C.
Conroy, D.
Bojesen, S.E.
Kaaks, R.
Vincent, D.
Bacot, F.
Tessier, D.C.
COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative,
UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology,
UK ProtecT Study Collaborators,
PRACTICAL Consortium,
Easton, D.F.
Eeles, R.A.
(2013). Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression. Hum mol genet,
Vol.22
(12),
pp. 2520-2528.
show abstract
Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease..