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Int J Cancer. 2019 Jul 18. doi: 10.1002/ijc.32577. [Epub ahead of print]

Family history of prostate cancer and the incidence of ERG- and phosphatase and tensin homolog-defined prostate cancer.

Author information

1
Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY.
2
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
3
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
4
Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
5
Department of Surgery, University of California, San Francisco, San Francisco, CA.
6
Department of Histopathology, St. James's Hospital and Trinity College Dublin Medical School, Dublin, Ireland.
7
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
8
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
9
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
10
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.
11
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
12
Department of Pathology, Johns Hopkins Bayview Medical Center, Baltimore, MD.
13
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
14
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA.

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

PMID:
31318977
DOI:
10.1002/ijc.32577

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