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Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry.
Chen, Fei; Madduri, Ravi K; Rodriguez, Alex A; Darst, Burcu F; Chou, Alisha; Sheng, Xin; Wang, Anqi; Shen, Jiayi; Saunders, Edward J; Rhie, Suhn K; Bensen, Jeannette T; Ingles, Sue A; Kittles, Rick A; Strom, Sara S; Rybicki, Benjamin A; Nemesure, Barbara; Isaacs, William B; Stanford, Janet L; Zheng, Wei; Sanderson, Maureen; John, Esther M; Park, Jong Y; Xu, Jianfeng; Wang, Ying; Berndt, Sonja I; Huff, Chad D; Yeboah, Edward D; Tettey, Yao; Lachance, Joseph; Tang, Wei; Rentsch, Christopher T; Cho, Kelly; Mcmahon, Benjamin H; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Sellers, Thomas A; Yamoah, Kosj; Murphy, Adam B; Crawford, Dana C; Patel, Alpa V; Bush, William S; Aldrich, Melinda C; Cussenot, Olivier; Petrovics, Gyorgy; Cullen, Jennifer; Neslund-Dudas, Christine M; Stern, Mariana C.
Afiliação
  • Chen F; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Madduri RK; Argonne National Laboratory, Lemont, IL, USA.
  • Rodriguez AA; Argonne National Laboratory, Lemont, IL, USA.
  • Darst BF; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Chou A; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Sheng X; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Wang A; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Shen J; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Saunders EJ; The Institute of Cancer Research, London, UK.
  • Rhie SK; Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Bensen JT; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Ingles SA; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Kittles RA; Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
  • Strom SS; Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
  • Rybicki BA; Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.
  • Nemesure B; Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, USA.
  • Isaacs WB; James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD, USA.
  • Stanford JL; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Zheng W; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Sanderson M; Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA.
  • John EM; Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Park JY; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
  • Xu J; Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
  • Wang Y; Department of Population Science, American Cancer Society, Kennesaw, GA, USA.
  • Berndt SI; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Huff CD; Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
  • Yeboah ED; University of Ghana Medical School, Accra, Ghana.
  • Tettey Y; Department of Pathology, University of Ghana, Accra, Ghana; Korle Bu Teaching Hospital, Accra, Ghana.
  • Lachance J; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
  • Tang W; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Rentsch CT; Yale School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
  • Cho K; Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Jamaica Plain, MA, USA.
  • Mcmahon BH; Theoretical Biology Division, Los Alamos National Lab, Los Alamos, NM, USA.
  • Biritwum RB; Korle Bu Teaching Hospital, Accra, Ghana.
  • Adjei AA; Department of Pathology, University of Ghana Medical School, Accra, Ghana.
  • Tay E; Korle Bu Teaching Hospital, Accra, Ghana.
  • Truelove A; Westat, Rockville, MD, USA.
  • Niwa S; Westat, Rockville, MD, USA.
  • Sellers TA; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
  • Yamoah K; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA; Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.
  • Murphy AB; Department of Urology, Northwestern University, Chicago, IL, USA.
  • Crawford DC; Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
  • Patel AV; Department of Population Science, American Cancer Society, Kennesaw, GA, USA.
  • Bush WS; Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
  • Aldrich MC; Division of Epidemiology, Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Cussenot O; Department of Urology and Predictive Onco-Urology Group, Sorbonne Université, GRC 5 Predictive Onco-Urology, APHP-Sorbonne Université, Paris, France; CeRePP, Tenon Hospital, Paris, France.
  • Petrovics G; Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Cullen J; Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Neslund-Dudas CM; Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.
  • Stern MC; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Eur Urol ; 84(1): 13-21, 2023 07.
Article em En | MEDLINE | ID: mdl-36872133
ABSTRACT

BACKGROUND:

Genetic factors play an important role in prostate cancer (PCa) susceptibility.

OBJECTIVE:

To discover common genetic variants contributing to the risk of PCa in men of African ancestry. DESIGN, SETTING, AND

PARTICIPANTS:

We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry. OUTCOME MEASUREMENTS AND STATISTICAL

ANALYSIS:

Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness. RESULTS AND

LIMITATIONS:

Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4).

CONCLUSIONS:

This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry. PATIENT

SUMMARY:

In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Predisposição Genética para Doença Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Aspecto: Patient_preference Limite: Humans / Male Idioma: En Revista: Eur Urol Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Predisposição Genética para Doença Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Aspecto: Patient_preference Limite: Humans / Male Idioma: En Revista: Eur Urol Ano de publicação: 2023 Tipo de documento: Article