| Title: |
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 |
| Authors: |
Schaid, DJ; McDonnell, SK; Liesel Fitzgerald; 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; Albright, LC; Teerlink, C; Xu, J; Isaacs, W; Ostrander, EA; Thibodeau, SN |
| Publication Year: |
2020 |
| Subject Terms: |
Cancer genetics; prostate cancer; exome sequencing; custom-capture sequencing; familial prostate cancer; genetic risk variants; whole-exome sequencing |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
102.100.100/555202 |
| Availability: |
https://figshare.com/articles/journal_contribution/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/22992182 |
| Rights: |
In Copyright |
| Accession Number: |
edsbas.8362BF76 |
| Database: |
BASE |