@article{0207ca9ce7594cd9b47ed21d8eccc2de,
title = "Family history of prostate cancer and the incidence of ERG- and phosphatase and tensin homolog-defined prostate cancer",
abstract = "Family history is among the strongest known risk factors for prostate cancer (PCa). Emerging data suggest molecular subtypes of PCa, including two somatic genetic aberrations: fusions of androgen-regulated promoters with ERG and, separately, phosphatase and tensin homolog (PTEN) loss. We examined associations between family history and incidence of these subtypes in 44,126 men from the prospective Health Professionals Follow-up Study. ERG and PTEN status were assessed by immunohistochemistry. Multivariable competing risks models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between self-reported family history of PCa and molecular subtypes of disease. Thirteen percent of men had a positive family history of PCa at baseline. During a median follow-up of 18.5 years, 5,511 PCa cases were diagnosed. Among them, 888 were assayed for ERG status (47% ERG-positive) and 715 were assayed for PTEN loss (14% PTEN null). Family history was more strongly associated with risk of ERG-negative (HR: 2.15; 95% CI: 1.71–2.70) than ERG-positive (HR: 1.49; 95% CI: 1.13–1.95) disease (pheterogeneity: 0.04). The strongest difference was among men with an affected father (HRERG-negative: 2.09; 95% CI: 1.64–2.66; HRERG-positive: 1.30; 95% CI: 0.96–1.76; pheterogeneity: 0.01). Family history of PCa was positively associated with both PTEN null (HR: 2.10; 95% CI: 1.26–3.49) and PTEN intact (HR: 1.72; 95% CI: 1.39–2.13) PCa (pheterogeneity: 0.47). Our results indicate that PCa family history may be positively associated with PCa in all ERG and PTEN subtypes, suggesting a role of genetic susceptibility in their development. It is possible that ERG-negative disease could be especially associated with positive family history.",
keywords = "PTEN, TMPRSS2:ERG, family history, molecular subtypes, prostate cancer",
author = "Dana Hashim and Gonzalez-Feliciano, {Amparo G.} and Ahearn, {Thomas U.} and Andreas Pettersson and Lauren Barber and Pernar, {Claire H.} and Ebot, {Ericka M.} and Masis Isikbay and Finn, {Stephen P.} and Giovannucci, {Edward L.} and Lis, {Rosina T.} and Massimo Loda and Giovanni Parmigiani and Tamara Lotan and Kantoff, {Philip W.} and Mucci, {Lorelei A.} and Graff, {Rebecca E.}",
note = "Funding Information: *Dana Hashim and Amparo G. Gonzalez-Feliciano contributed equally to this work Key words: prostate cancer, TMPRSS2:ERG, PTEN, family history, molecular subtypes Abbreviations: BMI: body mass index; CI: confidence interval; HPFS: Health Professionals Follow-up Study; HR: hazard ratio; MET: metabolic equivalent task; PCa: prostate cancer; PSA: prostate-specific antigen; PTEN: phosphatase and tensin homolog; TMA: tissue microarray Conflict of interest: P.W.K. does not have a conflict of interest, but it is his policy to report any and all disclosures as an author on a paper. To that end, as of July 10, 2019, he reports the following disclosures for the last 24-month period: he has investment interest in Context Therapeutics LLC, DRGT, Placon, Seer Biosciences, and Tarveda Therapeutics; he is a company board member for Context Therapeutics LLC; he is a consultant/advisory board member for Bavarian Nordic Immunotherapeutics, DRGT, GE Healthcare, Janssen, New England Research Institutes, Inc., OncoCellMDX, Progenity, Sanofi, Seer Biosciences, Tarveda Therapeutics, and Thermo Fisher; and he serves on data safety monitoring boards for Genentech/Roche and Merck. All other authors have no potential conflicts of interest to disclose. Grant sponsor: American Cancer Society - Ellison Foundation Postdoctoral Fellowship; Grant number: PF-14-140-01-CCE; Grant sponsor: National Institutes of Health; Grant numbers: T32 CA09001, P50 CA090381, R01 CA136578, R01 CA141298, R25 CA112355, U01 CA167552; Grant sponsor: Office of the Assistant Secretary of Defense for Health Affairs; Grant number: W81XWH-14-1-0250; Grant sponsor: Prostate Cancer Foundation DOI: 10.1002/ijc.32577 History: Received 27 Jan 2019; Accepted 28 Jun 2019; Online 18 Jul 2019 Correspondence to: Rebecca E. Graff, Department of Epidemiology & Biostatistics, University of California, San Francisco, Mission Hall: Global Health & Clinical Sciences Building, 550 16th Street, 2nd Floor, Box #0560, San Francisco, CA 94158, Tel.: (510) 847-7060, E-mail: rebecca.graff@ucsf.edu Funding Information: We would like to thank the participants and staff of the HPFS for their valuable contributions as well as the following state cancer registries for their help: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Virginia, Washington, and Wyoming. The authors assume full responsibility for analyses and interpretation of these data. This work was supported by the National Institutes of Health (grant numbers R01 CA136578, R01 CA141298, P50 CA090381, U01 CA167552, and R25 CA112355 to R.E.G. and T32 CA09001 to T.U.A., C.H.P., and E.M.E.); the Prostate Cancer Foundation Young Investigators Awards (to L.A.M. and T.L.); the American Cancer Society—Ellison Foundation Postdoctoral Fellowship (PF-14-140-01-CCE to T.U.A.); and the Office of the Assistant Secretary of Defense for Health Affairs under (Award No. W81XWH-14-1-0250 to E.M.E.). Publisher Copyright: {\textcopyright} 2019 UICC",
year = "2020",
month = may,
day = "15",
doi = "10.1002/ijc.32577",
language = "English (US)",
volume = "146",
pages = "2694--2702",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "10",
}