Daniel Hyuck-Min Kwon1, Hala T Borno2, Heather H Cheng3, Alicia Yiran Zhou4, Eric Jay Small2. 1. Department of Medicine, Division of Hematology and Oncology, University of California San Francisco, San Francisco, CA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA. Electronic address: Daniel.Kwon@ucsf.edu. 2. Department of Medicine, Division of Hematology and Oncology, University of California San Francisco, San Francisco, CA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA. 3. University of Washington School of Medicine, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA; Seattle Cancer Care Alliance Prostate Cancer Genetics Clinic, Seattle, WA. 4. Color Genomics, Burlingame, CA.
Abstract
BACKGROUND: Prostate cancer is among the most heritable cancers, and clinical testing for germline genetic variants based on ethnicity, disease features, and family history has recently become standard of care for men with advanced disease. It is not established whether prevalence of germline variants varies based on ethnicity or race. METHODS: We retrospectively examined germline genetic and clinical data of men reporting a diagnosis of prostate cancer referred to Color Genomics by a healthcare provider for testing of 30 genes associated with hereditary cancer risk. Variants were classified as pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign, or benign. P/LP and VUS prevalence was compared among subgroups classified by age at diagnosis, self-reported ethnicity, family history, and history of other cancer. RESULTS: We identified 1,351 men reporting a diagnosis of prostate cancer of any stage who underwent germline testing. Overall, 78% of men were Caucasian, 11% Ashkenazi Jewish, 3% African-American/Canadian (AAC), 2% Hispanic, 2% Asian/Pacific Islander (API), and 4% Other (multiple, unknown, Native-American). One-hundred eighty-seven men (13.8%) carried a P/LP variant, and the most prevalent P/LP variants were in BRCA2 (3.4%), CHEK2 (2.8%), MUTYH (1.8%), and ATM (1.7%). Age at diagnosis, ethnicity, type of family member with prostate cancer, and type of second cancer were not associated with risk of carrying any P/LP variant. Ashkenazi Jewish men (6.7%) were more likely to carry P/LP BRCA2 variants than Caucasian men (2.8%) (P < 0.05). Two-hundred eighty-four men (21.0%) carried a VUS, and AAC (36.6%) and API (33.3%) men were most likely to carry a VUS (P < 0.01). CONCLUSIONS: P/LP germline variants are prevalent in men with prostate cancer. AAC, Hispanic, and API men with prostate cancer are under-represented in studies of germline testing, potentially contributing to higher rates of VUS relative to Caucasian and Ashkenazi Jewish men. Further studies in these groups will facilitate reclassification of VUS, increasing opportunities for early detection, cancer risk modification, and targeted therapeutics. Published by Elsevier Inc.
BACKGROUND:Prostate cancer is among the most heritable cancers, and clinical testing for germline genetic variants based on ethnicity, disease features, and family history has recently become standard of care for men with advanced disease. It is not established whether prevalence of germline variants varies based on ethnicity or race. METHODS: We retrospectively examined germline genetic and clinical data of men reporting a diagnosis of prostate cancer referred to Color Genomics by a healthcare provider for testing of 30 genes associated with hereditary cancer risk. Variants were classified as pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign, or benign. P/LP and VUS prevalence was compared among subgroups classified by age at diagnosis, self-reported ethnicity, family history, and history of other cancer. RESULTS: We identified 1,351 men reporting a diagnosis of prostate cancer of any stage who underwent germline testing. Overall, 78% of men were Caucasian, 11% Ashkenazi Jewish, 3% African-American/Canadian (AAC), 2% Hispanic, 2% Asian/Pacific Islander (API), and 4% Other (multiple, unknown, Native-American). One-hundred eighty-seven men (13.8%) carried a P/LP variant, and the most prevalent P/LP variants were in BRCA2 (3.4%), CHEK2 (2.8%), MUTYH (1.8%), and ATM (1.7%). Age at diagnosis, ethnicity, type of family member with prostate cancer, and type of second cancer were not associated with risk of carrying any P/LP variant. Ashkenazi Jewish men (6.7%) were more likely to carry P/LP BRCA2 variants than Caucasian men (2.8%) (P < 0.05). Two-hundred eighty-four men (21.0%) carried a VUS, and AAC (36.6%) and API (33.3%) men were most likely to carry a VUS (P < 0.01). CONCLUSIONS: P/LP germline variants are prevalent in men with prostate cancer. AAC, Hispanic, and API men with prostate cancer are under-represented in studies of germline testing, potentially contributing to higher rates of VUS relative to Caucasian and Ashkenazi Jewish men. Further studies in these groups will facilitate reclassification of VUS, increasing opportunities for early detection, cancer risk modification, and targeted therapeutics. Published by Elsevier Inc.
Entities:
Keywords:
Disparities; Germline mutation; Prostate cancer
Authors: Shamini Selvarajah; Kasmintan A Schrader; Michael P Kolinsky; Ricardo A Rendon; Soufiane El Hallani; Neil E Fleshner; Sebastien J Hotte; Justin Lorentz; Karen Panabaker; Renée Perrier; Frédéric Pouliot; Alan Spatz; Stephen Yip; Kim N Chi Journal: Can Urol Assoc J Date: 2022-10 Impact factor: 2.052
Authors: Simon Easteal; Ruth M Arkell; Renzo F Balboa; Shayne A Bellingham; Alex D Brown; Tom Calma; Matthew C Cook; Megan Davis; Hugh J S Dawkins; Marcel E Dinger; Michael S Dobbie; Ashley Farlow; Kylie G Gwynne; Azure Hermes; Wendy E Hoy; Misty R Jenkins; Simon H Jiang; Warren Kaplan; Stephen Leslie; Bastien Llamas; Graham J Mann; Brendan J McMorran; Rebekah E McWhirter; Cliff J Meldrum; Shivashankar H Nagaraj; Saul J Newman; Jack S Nunn; Lyndon Ormond-Parker; Neil J Orr; Devashi Paliwal; Hardip R Patel; Glenn Pearson; Greg R Pratt; Boe Rambaldini; Lynette W Russell; Ravi Savarirayan; Matthew Silcocks; John C Skinner; Yassine Souilmi; Carola G Vinuesa; Gareth Baynam Journal: Am J Hum Genet Date: 2020-08-06 Impact factor: 11.025
Authors: Mark J Berger; Hannah E Williams; Ryan Barrett; Anjali D Zimmer; Wendy McKennon; Huy Hong; Jeremy Ginsberg; Alicia Y Zhou; Cynthia L Neben Journal: Database (Oxford) Date: 2020-01-01 Impact factor: 3.451
Authors: Hala T Borno; Anobel Y Odisho; Christine M Gunn; Magdalena Pankowska; Jennifer R Rider Journal: Urol Oncol Date: 2020-11-04 Impact factor: 2.954
Authors: Veda N Giri; Karen E Knudsen; William K Kelly; Heather H Cheng; Kathleen A Cooney; Michael S Cookson; William Dahut; Scott Weissman; Howard R Soule; Daniel P Petrylak; Adam P Dicker; Saud H AlDubayan; Amanda E Toland; Colin C Pritchard; Curtis A Pettaway; Mary B Daly; James L Mohler; J Kellogg Parsons; Peter R Carroll; Robert Pilarski; Amie Blanco; Ashley Woodson; Alanna Rahm; Mary-Ellen Taplin; Thomas J Polascik; Brian T Helfand; Colette Hyatt; Alicia K Morgans; Felix Feng; Michael Mullane; Jacqueline Powers; Raoul Concepcion; Daniel W Lin; Richard Wender; James Ryan Mark; Anthony Costello; Arthur L Burnett; Oliver Sartor; William B Isaacs; Jianfeng Xu; Jeffrey Weitzel; Gerald L Andriole; Himisha Beltran; Alberto Briganti; Lindsey Byrne; Anne Calvaresi; Thenappan Chandrasekar; David Y T Chen; Robert B Den; Albert Dobi; E David Crawford; James Eastham; Scott Eggener; Matthew L Freedman; Marc Garnick; Patrick T Gomella; Nathan Handley; Mark D Hurwitz; Joseph Izes; R Jeffrey Karnes; Costas Lallas; Lucia Languino; Stacy Loeb; Ana Maria Lopez; Kevin R Loughlin; Grace Lu-Yao; S Bruce Malkowicz; Mark Mann; Patrick Mille; Martin M Miner; Todd Morgan; Jose Moreno; Lorelei Mucci; Ronald E Myers; Sarah M Nielsen; Brock O'Neil; Wayne Pinover; Peter Pinto; Wendy Poage; Ganesh V Raj; Timothy R Rebbeck; Charles Ryan; Howard Sandler; Matthew Schiewer; E Michael D Scott; Brittany Szymaniak; William Tester; Edouard J Trabulsi; Neha Vapiwala; Evan Y Yu; Charnita Zeigler-Johnson; Leonard G Gomella Journal: J Clin Oncol Date: 2020-06-09 Impact factor: 44.544
Authors: Elisa M Ledet; Earle F Burgess; Alexandra O Sokolova; Ellen B Jaeger; Whitley Hatton; Marcus Moses; Patrick Miller; Patrick Cotogno; Jodi Layton; Pedro Barata; Brian E Lewis; Mari Nakazawa; Jason Zhu; Beth Dellinger; Sara Elrefai; Nellie N Nafissi; Jan B Egan; Neal Shore; Rana R McKay; Alan H Bryce; Heather H Cheng; Emmanuel S Antonarakis; Oliver Sartor Journal: Prostate Date: 2021-04-01 Impact factor: 4.104