Skip to main content
Journal cover image

Two-stage Study of Familial Prostate Cancer by Whole-exome Sequencing and Custom Capture Identifies 10 Novel Genes Associated with the Risk of Prostate Cancer.

Publication ,  Journal Article
Schaid, DJ; McDonnell, SK; FitzGerald, LM; DeRycke, L; Fogarty, Z; Giles, GG; MacInnis, RJ; Southey, MC; Nguyen-Dumont, T; Cancel-Tassin, G ...
Published in: Eur Urol
March 2021

BACKGROUND: Family history of prostate cancer (PCa) is a well-known risk factor, and both common and rare genetic variants are associated with the disease. OBJECTIVE: To detect new genetic variants associated with PCa, capitalizing on the role of family history and more aggressive PCa. DESIGN, SETTING, AND PARTICIPANTS: A two-stage design was used. In stage one, whole-exome sequencing was used to identify potential risk alleles among affected men with a strong family history of disease or with more aggressive disease (491 cases and 429 controls). Aggressive disease was based on a sum of scores for Gleason score, node status, metastasis, tumor stage, prostate-specific antigen at diagnosis, systemic recurrence, and time to PCa death. Genes identified in stage one were screened in stage two using a custom-capture design in an independent set of 2917 cases and 1899 controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Frequencies of genetic variants (singly or jointly in a gene) were compared between cases and controls. RESULTS AND LIMITATIONS: Eleven genes previously reported to be associated with PCa were detected (ATM, BRCA2, HOXB13, FAM111A, EMSY, HNF1B, KLK3, MSMB, PCAT1, PRSS3, and TERT), as well as an additional 10 novel genes (PABPC1, QK1, FAM114A1, MUC6, MYCBP2, RAPGEF4, RNASEH2B, ULK4, XPO7, and THAP3). Of these 10 novel genes, all but PABPC1 and ULK4 were primarily associated with the risk of aggressive PCa. CONCLUSIONS: Our approach demonstrates the advantage of gene sequencing in the search for genetic variants associated with PCa and the benefits of sampling patients with a strong family history of disease or an aggressive form of disease. PATIENT SUMMARY: Multiple genes are associated with prostate cancer (PCa) among men with a strong family history of this disease or among men with an aggressive form of PCa.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Eur Urol

DOI

EISSN

1873-7560

Publication Date

March 2021

Volume

79

Issue

3

Start / End Page

353 / 361

Location

Switzerland

Related Subject Headings

  • Urology & Nephrology
  • Trypsin
  • Protein Serine-Threonine Kinases
  • Prostatic Neoplasms
  • Neoplasm Grading
  • Male
  • Humans
  • Guanine Nucleotide Exchange Factors
  • Genes, BRCA2
  • Exome Sequencing
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Schaid, D. J., McDonnell, S. K., FitzGerald, L. M., DeRycke, L., Fogarty, Z., Giles, G. G., … Thibodeau, S. N. (2021). Two-stage Study of Familial Prostate Cancer by Whole-exome Sequencing and Custom Capture Identifies 10 Novel Genes Associated with the Risk of Prostate Cancer. Eur Urol, 79(3), 353–361. https://doi.org/10.1016/j.eururo.2020.07.038
Schaid, Daniel J., Shannon K. McDonnell, Liesel M. FitzGerald, Lissa DeRycke, Zachary Fogarty, Graham G. Giles, Robert J. MacInnis, et al. “Two-stage Study of Familial Prostate Cancer by Whole-exome Sequencing and Custom Capture Identifies 10 Novel Genes Associated with the Risk of Prostate Cancer.Eur Urol 79, no. 3 (March 2021): 353–61. https://doi.org/10.1016/j.eururo.2020.07.038.
Schaid DJ, McDonnell SK, FitzGerald LM, DeRycke L, Fogarty Z, Giles GG, et al. Two-stage Study of Familial Prostate Cancer by Whole-exome Sequencing and Custom Capture Identifies 10 Novel Genes Associated with the Risk of Prostate Cancer. Eur Urol. 2021 Mar;79(3):353–61.
Schaid, Daniel J., et al. “Two-stage Study of Familial Prostate Cancer by Whole-exome Sequencing and Custom Capture Identifies 10 Novel Genes Associated with the Risk of Prostate Cancer.Eur Urol, vol. 79, no. 3, Mar. 2021, pp. 353–61. Pubmed, doi:10.1016/j.eururo.2020.07.038.
Schaid DJ, McDonnell SK, FitzGerald LM, DeRycke L, Fogarty Z, Giles GG, MacInnis RJ, Southey MC, Nguyen-Dumont T, Cancel-Tassin G, Cussenot O, Whittemore AS, Sieh W, Ioannidis NM, Hsieh C-L, Stanford JL, Schleutker J, Cropp CD, Carpten J, Hoegel J, Eeles R, Kote-Jarai Z, Ackerman MJ, Klein CJ, Mandal D, Cooney KA, Bailey-Wilson JE, Helfand B, Catalona WJ, Wiklund F, Riska S, Bahetti S, Larson MC, Cannon Albright L, Teerlink C, Xu J, Isaacs W, Ostrander EA, Thibodeau SN. Two-stage Study of Familial Prostate Cancer by Whole-exome Sequencing and Custom Capture Identifies 10 Novel Genes Associated with the Risk of Prostate Cancer. Eur Urol. 2021 Mar;79(3):353–361.
Journal cover image

Published In

Eur Urol

DOI

EISSN

1873-7560

Publication Date

March 2021

Volume

79

Issue

3

Start / End Page

353 / 361

Location

Switzerland

Related Subject Headings

  • Urology & Nephrology
  • Trypsin
  • Protein Serine-Threonine Kinases
  • Prostatic Neoplasms
  • Neoplasm Grading
  • Male
  • Humans
  • Guanine Nucleotide Exchange Factors
  • Genes, BRCA2
  • Exome Sequencing