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Clinical Research

Common variation in BRCA1 may have a role in progression to lethal prostate cancer after radiation treatment

Prostate Cancer and Prostatic Diseases volume 19, pages 197–201 (2016)Cite this article

Subjects

Abstract

BACKGROUND:

To evaluate whether single-nucleotide polymorphisms (SNPs) reflecting common variation in the tumor suppressor BRCA1 affect prostate cancer outcomes. Because radiation therapy (RT) induces DNA damage, we hypothesized that common variation in BRCA1 has a role in progression to lethal prostate cancer, particularly in patients receiving RT.

Methods:

We followed 802 men diagnosed with localized prostate cancer (cT1-T3/N0/M0) who were treated with RT in the US Health Professionals Follow-up Study (HPFS) and Physicians’ Health Study (PHS), for progression to lethal prostate cancer. Six SNPs (rs3737559, rs1799950, rs799923, rs915945, rs4474733 and rs8176305) were genotyped in HPFS to capture common variation across BRCA1. rs4474733 and rs8176305 were also evaluated in the PHS cohort. Cox proportional hazards models were used to estimate per-allele hazard ratios (HR) and 95% confidence intervals (CI) stratified by primary treatment.

Results:

In the RT group (n=802), 71 men progressed to lethal disease during a mean follow-up of 12 years. We found that two SNPs, rs4473733 (HR: 0.65; 95% CI 0.42–0.99) and rs8176305 (HR: 2.03; 95% CI 1.33–3.10), were associated with lethal prostate cancer in men receiving RT.

Conclusions:

Common variation in BRCA1 may influence clinical outcomes in patients receiving RT for localized prostate cancer by modifying the response to RT. Our findings merit further follow-up studies to validate these SNPs and better understand their functional and biological significance.

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Acknowledgements

We are grateful to the participants and staff of the HPFS and PHS cohorts for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The Dana-Farber/Harvard Center Genotyping Core Facility performed the genotyping for this project. The authors assume full responsibility for analyses and interpretation of these data. This project was supported by the US Army Prostate Cancer Program Idea Development Award. IMS supported by (T32 CA-09001) and a Department of Defense Prostate Cancer Research Program post-doctoral training award. PLN was supported by a grant from an anonymous family foundation and LAM and PLN are supported by the Prostate Cancer Foundation. PHS was supported by grants CA34944, CA40360, CA097193, HL26490 and HL34595. HPFS was supported by grants CA133891, CA141298, and P01CA055075 and UM1 CA167552.

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Authors and Affiliations

  1. Department of Urology, Massachusetts General Hospital, Boston, MA, USA

    A Sanchez

  2. Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    J D Schoenfeld, P L Nguyen & D Chowdhury

  3. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    M Fiorentino, M J Stampfer, H D Sesso, E Giovannucci, L A Mucci & I M Shui

  4. Channing Division of Network Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA

    M J Stampfer, E Giovannucci & L A Mucci

  5. Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA

    M J Stampfer & H D Sesso

  6. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    I M Shui

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  1. A Sanchez
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  2. J D Schoenfeld
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Correspondence to A Sanchez.

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Sanchez, A., Schoenfeld, J., Nguyen, P. et al. Common variation in BRCA1 may have a role in progression to lethal prostate cancer after radiation treatment. Prostate Cancer Prostatic Dis 19, 197–201 (2016). https://doi.org/10.1038/pcan.2016.4

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