Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness: Cancer Research

V.L. Patel, E.L. Busch, T.M. Friebel, A. Cronin, G. Leslie, L. McGuffog, J. Adlard, S. Agata, B.A. Agnarsson, M. Ahmed, K. Aittom, E. Alducci, I.L. Andrulis, A. Arason, N. Arnold, G. Artioli, B. Arver, B. Auber, J. Azzollini, J. BalmañaR.B. Barkardottir, D.R. Barnes, A. Barroso, D. Barrowdale, M. Belotti, J. Benitez, B. Bertelsen, M.J. Blok, I. Bodrogi, V. Bonadona, B. Bonanni, D. Bondavalli, S.E. Boonen, J. Borde, A. Borg, A.R. Bradbury, A. Brady, C. Brewer, J. Brunet, B. Buecher, S.S. Buys, S. Cabezas-Camarero, T. Caldes, A. Caliebe, M.A. Caligo, M. Calvello, I.G. Campbell, I. Carnevali, E. Carrasco, T.L. Chan, A.T.W. Chu, W.K. Chung, K.B.M. Claes, J. Cook, L. Cortesi, F.J. Couch, M.B. Daly, G. Damante, E. Darder, R. Davidson, M. De La Hoya, L. Della Puppa, J. Dennis, O. Díez, Y.C. Ding, N. Ditsch, S.M. Domchek, A. Donaldson, B. Dworniczak, D.F. Easton, D.M. Eccles, R.A. Eeles, H. Ehrencrona, B. Ejlertsen, C. Engel, D.G. Evans, L. Faivre, U. Faust, L. Feliubadalo, L. Foretova, F. Fostira, G. Fountzilas, D. Frost, V. García-Barberan, P. Garre, M. Gauthier-Villars, L. Geczi, A. Gehrig, A.-M. Gerdes, P. Gesta, G. Giannini, G. Glendon, A.K. Godwin, D.E. Goldgar, M.H. Greene, A.M. Gutierrez-Barrera, E. Hahnen, U. Hamann, J. Hauke, N. Herold, F.B.L. Hogervorst, E. Honisch, J.L. Hopper, P.J. Hulick, L. Izatt, A. Jager, P. James, R. Janavicius, U.B. Jensen, T.D. Jensen, O.Th. Johannsson, E.M. John, V. Joseph, E. Kang, K. Kast, J.I. Kiiski, S.-W. Kim, Z. Kim, K.-P. Ko, I. Konstantopoulou, G. Kramer, L. Krogh, T.A. Kruse, A. Kwong, M. Larsen, C. Lasset, C. Lautrup, C. Lazaro, J. Lee, J.W. Lee, M.H. Lee, J. Lemke, F. Lesueur, A. Liljegren, A. Lindblom, P. Llovet, A. Lopez-Fernandez, I. Lopez-Perolio, V. Lorca, J.T. Loud, E.S.K. Ma, P.L. Mai, S. Manoukian, V. Mari, L. Martin, L. Matricardi, N. Mebirouk, V. Medici, H.E.J. Meijers-Heijboer, A. Meindl, A.R. Mensenkamp, C. Miller, D.M. Gomes, M. Montagna, T.M. Mooij, L. Moserle, E. Mouret-Fourme, A.M. Mulligan, K.L. Nathanson, M. Navratilova, H. Nevanlinna, D. Niederacher, F.C. Cilius Nielsen, L. Nikitina-Zake, K. Offit, E. Olah, O.I. Olopade, K.-R. Ong, A. Osorio, C.-E. Ott, D. Palli, S.K. Park, M.T. Parsons, I.S. Pedersen, B. Peissel, A. Peixoto, P. Perez-Segura, P. Peterlongo, A.H. Petersen, M.E. Porteous, M.A. Pujana, P. Radice, J. Ramser, J. Rantala, M.U. Rashid, K. Rhiem, P. Rizzolo, M.E. Robson, M.A. Rookus, C.M. Rossing, K.J. Ruddy, C. Santos, C. Saule, R. Scarpitta, R.K. Schmutzler, H. Schuster, L. Senter, C.M. Seynaeve, P.D. Shah, P. Sharma, V.Y. Shin, V. Silvestri, J. Simard, C.F. Singer, A.-B. Skytte, K. Snape, A.R. Solano, P. Soucy, M.C. Southey, A.B. Spurdle, L. Steele, D. Steinemann, D. Stoppa-Lyonnet, A. Stradella, L. Sunde, C. Sutter, Y.Y. Tan, M.R. Teixeira, S.H. Teo, M. Thomassen, M.G. Tibiletti, M. Tischkowitz, S. Tognazzo, A.E. Toland, S. Tommasi, D. Torres, A. Toss, A.H. Trainer, N. Tung, C.J. Van Asperen, F.H. Van Der Baan, L.E. Van Der Kolk, R.B. Van Der Luijt, L.P. Van Hest, L. Varesco, R. Varon-Mateeva, A. Viel, J. Vierstrate, R. Villa, A. Von Wachenfeldt, P. Wagner, S. Wang-Gohrke, B. Wappenschmidt, J.N. Weitzel, G. Wieme, S. Yadav, D. Yannoukakos, S.-Y. Yoon, C. Zanzottera, K.K. Zorn, A.V. D’Amico, M.L. Freedman, M.M. Pomerantz, G. Chenevix-Trench, A.C. Antoniou, S.L. Neuhausen, L. Ottini, H.R. Nielsen, T.R. Rebbeck

Research output: Contribution to journalArticlepeer-review

Abstract

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8þ) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 30 region of BRCA2 (c.7914þ) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR ¼ 1.78; 95% confidence interval (CI), 1.25–2.52; P ¼ 0.001], as well as elevated risk of Gleason 8þ prostate cancer (HR ¼ 3.11; 95% CI, 1.63–5.95; P ¼ 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR ¼ 2.83; 95% CI, 1.71–4.68; P ¼ 0.00004) and elevated risk of Gleason 8þ prostate cancer (HR ¼ 4.95; 95% CI, 2.12–11.54; P ¼ 0.0002). No genotype–phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. © 2020 American Association for Cancer Research.
Original languageEnglish
Pages (from-to)624-638
Number of pages15
JournalCancer Res.
Volume80
Issue number3
DOIs
Publication statusPublished - 2020

Keywords

  • BRCA1 protein
  • BRCA2 protein
  • BRCA1 protein, human
  • BRCA2 protein, human
  • Article
  • cancer diagnosis
  • cancer grading
  • cancer risk
  • cohort analysis
  • disease severity
  • gene structure
  • genetic association
  • genetic risk
  • germ line
  • Gleason score
  • heterozygosity
  • human
  • male
  • priority journal
  • prostate cancer
  • tumor invasion
  • tumor suppressor gene
  • adolescent
  • adult
  • aged
  • genetic association study
  • genetic predisposition
  • genetics
  • genomics
  • heterozygote
  • middle aged
  • mutation
  • pathology
  • procedures
  • prognosis
  • prostate tumor
  • risk factor
  • very elderly
  • young adult
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • BRCA1 Protein
  • BRCA2 Protein
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genomics
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Prostatic Neoplasms
  • Risk Factors
  • Young Adult

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